M100-S15Vol. 25 No. 1
Replaces M100-S14January 2005 Vol. 24 No. 1
Performance Standards for AntimicrobialSusceptibility Testing; Fifteenth Informational Supplement
This document provides updated tables for the Clinical and Laboratory StandardsInstitute (CLSI)/NCCLS antimicrobial susceptibility testing standards M2-A8 andM7-A6.An informational supplement for global application developed through the Clinical andLaboratory Standards Institute consensus process.
The Clinical and Laboratory Standards Institute (CLSI)(formerly NCCLS) is an international, interdisciplinary,nonprofit, standards-developing, and educationalorganization that promotes the development and use ofvoluntary consensus standards and guidelines within thehealthcare community. It is recognized worldwide for theapplication of its unique consensus process in thedevelopment of standards and guidelines for patienttesting and related healthcare issues. Our process is basedon the principle that consensus is an effective and cost-effective way to improve patient testing and healthcareservices.
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PUBLICATIONS
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Our standards and guidelines represent a consensusopinion on good practices and reflect the substantialagreement by materially affected, competent, andinterested parties obtained by following CLSI’sestablished consensus procedures. Provisions in CLSIstandards and guidelines may be more or less stringentthan applicable regulations. Consequently, conformanceto this voluntary consensus document does not relieve theuser of responsibility for compliance with applicableregulations.
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Clinical and Laboratory Standards InstituteProviding NCCLS standards and guidelines, ISO/TC 212 standards, and ISO/TC 76 standards
1
Performance Standards for Antimicrobial Susceptibility Testing;Fifteenth Informational Supplement
Abstract
The supplemental information presented in this document is intended for use with the antimicrobialsusceptibility testing procedures published in the following Clinical and Laboratory Standards Institute(CLSI)/NCCLS approved standards: M2-A8—Performance Standards for Antimicrobial DiskSusceptibility Tests; Approved Standard—Eighth Edition; and M7-A6—Methods for DilutionAntimicrobial Susceptibility Tests for Bacteria That Grow Aerobically; Approved Standard—Sixth Edition.The standards contain information about both disk (M2) and dilution (M7) test procedures for aerobicbacteria.
Clinicians depend heavily on information from the clinical microbiology laboratory for treatment of theirseriously ill patients. The clinical importance of antimicrobial susceptibility test results requires that thesetests be done under optimal conditions and that laboratories have the capability to provide results for thenewest antimicrobial agents.
The tabular information presented here represents the most current information for drug selection,interpretation, and quality control using the procedures standardized in M2 and M7. Users should replacethe tables published earlier with these new tables. (Changes in the tables since the most recent editionappear in boldface type.)
Clinical and Laboratory Standards Institute. Performance Standards for Antimicrobial SusceptibilityTesting; Fifteenth Informational Supplement. CLSI document M100-S15 (ISBN 1-56238-556-9). Clinicaland Laboratory Standards Institute, 940 West Valley Road, Suite 1400, Wayne, Pennsylvania 19087-1898USA, 2005.
The data in the interpretive tables in this supplement are valid only if themethodologies in M2-A8—Performance Standards for Antimicrobial DiskSusceptibility Tests; Approved Standard—Eighth Edition; and M7-A6—Methods forDilution Antimicrobial Susceptibility Tests for Bacteria That Grow Aerobically; Approved Standard—Sixth Edition are followed.
Vol. 25 No. 1 M100-S15
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January 2005 M100-S15
Volume 25 Number 1
Matthew A. Wikler, M.D., M.B.A., FIDSAFranklin R. Cockerill, III, M.D.William A. Craig, M.D.Michael N. Dudley, Pharm.D.George M. Eliopoulos, M.D.David W. Hecht, M.D.Janet F. Hindler, MCLS, M.T.(ASCP)Donald E. Low, M.D.Daniel J. Sheehan, Ph.D.Fred C. Tenover, Ph.D., ABMMJohn D. Turnidge, M.D.Melvin P. Weinstein, M.D.Barbara L. Zimmer, Ph.D.
Mary Jane Ferraro, Ph.D., M.P.H.Jana M. Swenson, M.M.Sc.
M100-S15ISBN 1-56238-556-9ISSN 0273-3099
Performance Standards for Antimicrobial Susceptibility Testing;Fifteenth Informational Supplement
January 2005 M100-S15
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This publication is protected by copyright. No part of it may be reproduced, stored in a retrieval system,transmitted, or made available in any form or by any means (electronic, mechanical, photocopying,recording, or otherwise) without prior written permission from Clinical and Laboratory Standards Institute,except as stated below.
Clinical and Laboratory Standards Institute hereby grants permission to reproduce limited portions of thispublication for use in laboratory procedure manuals at a single site, for interlibrary loan, or for use ineducational programs provided that multiple copies of such reproduction shall include the followingnotice, be distributed without charge, and, in no event, contain more than 20% of the document’s text.
Reproduced with permission, from CLSI/NCCLS publication M100-S15—PerformanceStandards for Antimicrobial Susceptibility Testing; Fifteenth Informational Supplement(ISBN 1-56238-556-9). Copies of the current edition may be obtained from Clinical andLaboratory Standards Institute, 940 West Valley Road, Suite 1400, Wayne, Pennsylvania19087-1898, USA.
Permission to reproduce or otherwise use the text of this document to an extent that exceeds theexemptions granted here or under the Copyright Law must be obtained from Clinical and LaboratoryStandards Institute by written request. To request such permission, address inquiries to the Executive VicePresident, Clinical and Laboratory Standards Institute, 940 West Valley Road, Suite 1400, Wayne,Pennsylvania 19087-1898, USA.
Copyright ©2005. Clinical and Laboratory Standards Institute.
Suggested Citation
(Clinical and Laboratory Standards Institute/NCCLS. Performance Standards for AntimicrobialSusceptibility Testing; Fifteenth Informational Supplement. CLSI/NCCLS document M100-S15 [ISBN 1-56238-556-9]. Clinical and Laboratory Standards Institute, 940 West Valley Road, Suite 1400, Wayne,Pennsylvania 19087-1898 USA, 2005.)
Fifteenth Informational Supplement Eleventh Informational SupplementJanuary 2005 January 2001
Fourteenth Informational Supplement Tenth Informational SupplementJanuary 2004 January 2000
Thirteenth Informational Supplement Ninth Informational SupplementJanuary 2003 January 1999
Twelfth Informational Supplement Eighth Informational SupplementJanuary 2002 January 1998
ISBN 1-56238-556-9ISSN 0273-3099
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Committee Membership
Area Committee on Microbiology
Mary Jane Ferraro, Ph.D., M.P.H.ChairholderMassachusetts General HospitalBoston, Massachusetts
James H. Jorgensen, Ph.D.Vice-ChairholderUniversity of Texas Health ScienceCenterSan Antonio, Texas
Donald R. Callihan, Ph.D.BD Diagnostic SystemsSparks, Maryland
David L. Sewell, Ph.D.Veterans Affairs Medical CenterPortland, Oregon
Thomas R. Shryock, Ph.D.Lilly Research LaboratoriesGreenfield, Indiana
Jana M. Swenson, M.M.Sc.Centers for Disease Control andPreventionAtlanta, Georgia
Michael L. Wilson, M.D.Denver Health Medical CenterDenver, Colorado
Advisors
Ellen Jo Baron, Ph.D.Stanford Univ. Hospital & MedicalSchoolStanford, California
Lynne S. Garcia, M.S.LSG & AssociatesSanta Monica, California
Richard L. Hodinka, Ph.D.Children’s Hospital of PhiladelphiaPhiladelphia, Pennsylvania
Michael A. Pfaller, M.D.University of Iowa College of MedicineIowa City, Iowa
Robert P. Rennie, Ph.D.University of Alberta HospitalEdmonton, Alberta, Canada
Melvin P. Weinstein, M.D.Robert Wood Johnson Medical SchoolNew Brunswick, New Jersey
Gail L. Woods, M.D.ARUP Research InstituteSalt Lake City, Utah
Subcommittee on Antimicrobial Susceptibility Testing
Matthew A. Wikler, M.D., M.B.A.,FIDSAChairholderPeninsula Pharmaceuticals, Inc.Alameda, California
Franklin R. Cockerill, III, M.D.Mayo Clinic/Mayo FoundationRochester, Minnesota
William A. Craig, M.D.University of WisconsinMadison, Wisconsin
Michael N. Dudley, Pharm.D.Diversa CorporationSan Diego, California
George M. Eliopoulos, M.D.Beth Israel Deaconess Medical CenterBoston, Massachusetts
David W. Hecht, M.D.Loyola University Medical CenterMaywood, Illinois
Janet F. Hindler, MCLS, M.T.(ASCP)UCLA Medical CenterLos Angeles, California
Donald E. Low, M.D.Mount Sinai HospitalToronto, Ontario, Canada
Daniel J. Sheehan, Ph.D.Pfizer Inc.New York, New York
Fred C. Tenover, Ph.D., ABMMCenters for Disease Control andPreventionAtlanta, Georgia
John D. Turnidge, M.D.Women’s and Children’s HospitalNorth Adelaide, Australia
Melvin P. Weinstein, M.D.Robert Wood Johnson Medical SchoolNew Brunswick, New Jersey
Barbara L. Zimmer, Ph.D.Dade Behring MicroScanWest Sacramento, California
Advisors
Patricia A. Bradford, Ph.D.Wyeth ResearchPearl River, New York
John S. Bradley, M.D.Children’s Hospital and Health CenterSan Diego, California
Steven D. Brown, Ph.D.The Clinical Microbiology InstituteWilsonville, Oregon
Karen Bush, Ph.D.Johnson & Johnson PharmaceuticalResearch InstituteRaritan, New Jersey
Robert K. Flamm, Ph.D.Focus Technologies, Inc.Herndon, Virginia
Lawrence V. Friedrich, Pharm.D.Cubist PharmaceuticalsMt. Pleasant, South Carolina
Dwight J. Hardy, Ph.D.University of Rochester MedicalCenterRochester, New York
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Advisors (Continued)
Yoichi Hirakata, M.D., Ph.D.Nagasaki University School ofMedicine and DentistryNagasaki, Japan
Ronald N. Jones, M.D.The JONES Group/JMINorth Liberty, Iowa
Gunnar Kahlmeter, M.D., Ph.D.ESCMIDSweden
John E. McGowan, Jr., M.D.Emory University, Rollins School ofPublic HealthAtlanta, Georgia
Linda A. Miller, Ph.D.GlaxoSmithKlineCollegeville, Pennsylvania
Susan D. Munro, M.T.(ASCP)Stanford University Hospital andClinicsStanford, California
Charles H. Nightingale, Ph.D.Hartford HospitalHartford, Connecticut
John H. Powers, III, M.D., FACPFDA Center for Drug Evaluation andResearchRockville, Maryland
L. Barth Reller, M.D.Duke University Medical CenterDurham, North Carolina
Robert P. Rennie, Ph.D.University of Alberta HospitalEdmonton, Alberta, Canada
Sally Selepak, M.T.(ASCP)FDA Center for Devices andRadiological HealthRockville, Maryland
Jana M. Swenson, M.M.Sc.Centers for Disease Control andPreventionAtlanta, Georgia
George H. Talbot, M.D.Talbot Advisors LLCWayne, Pennsylvania
Staff
Clinical and Laboratory StandardsInstitute Wayne, Pennsylvania
Tracy A. Dooley, M.L.T.(ASCP)Staff Liaison
Donna M. WilhelmEditor
Melissa A. LewisAssistant Editor
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Abstract . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1
Committee Membership. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5
Updated Information in This Edition . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11
Subcommittee on Antimicrobial Susceptibility Testing Mission Statement . . . . . . . . . . . . . . . . . . . . 17
M2-A8 Performance Standards for Antimicrobial Disk Susceptibility Tests;Approved Standard—Eighth Edition
Introduction to Tables 1 through 1A and 2A through 2I for Use With M2-A8—Disk Diffusion. . . . 19
Table 1. Suggested Groupings of U.S. FDA-Approved Antimicrobial Agents That Should BeConsidered for Routine Testing and Reporting on Nonfastidious Organisms by Clinical MicrobiologyLaboratories . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 24
Table 1A. Suggested Groupings of U.S. FDA-Approved Antimicrobial Agents That Should BeConsidered for Routine Testing and Reporting on Fastidious Organisms by Clinical MicrobiologyLaboratories . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 30
Tables 2A-2I. Zone Diameter Interpretive Standards and Equivalent Minimal InhibitoryConcentration (MIC) Breakpoints for:
2A. Enterobacteriaceae . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 34
2B. Pseudomonas aeruginosa, Acinetobacter spp., Stenotrophomonas maltophilia, and Burkholderiacepacia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 40
2C. Staphylococcus spp.. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 44
2D. Enterococcus spp. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 52
2E. Haemophilus spp. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 56
2F. Neisseria gonorrhoeae . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 60
2G. Streptococcus pneumoniae. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 64
2H. Streptococcus spp. Other Than Streptococcus pneumoniae . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 66
2I. Vibrio cholerae . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 69
Table 3. Acceptable Limits for Quality Control Strains Used to Monitor Accuracy of Disk DiffusionTesting of Nonfastidious Organisms (Using Mueller-Hinton Medium Without Blood or OtherSupplements) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 70
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Table 3A. Acceptable Limits for Quality Control Strains Used to Monitor Accuracy of Disk DiffusionTesting of Fastidious Organisms . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 72
Table 3B. Reference Guide to Quality Control Testing Frequency. . . . . . . . . . . . . . . . . . . . . . . . . . . 74
Table 4. Suggestions for Verification of Antimicrobial Susceptibility Test Results and Confirmationof Organism Identification . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 76
Glossary I (Part 1). ß-lactams: Class and Subclass Designation and Generic Name . . . . . . . . . . . . . 78
Glossary I (Part 2). Non-ß-lactams: Class and Subclass Designation and Generic Name . . . . . . . . . 79
Glossary II. Abbreviations/Routes of Administration/Drug Class for Antimicrobial Agents Listed inM100-S15. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 80
List of Identical Abbreviations Used for More Than One Antimicrobial Agent in U.S. DiagnosticProducts . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 83
Summary of Comments and Subcommittee Responses (M2-Disk Diffusion) . . . . . . . . . . . . . . . . . . 84
M7-A6 Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria That Grow Aerobically; Approved Standard—Sixth Edition
Introduction to Tables 1 Through 1B and 2A Through 2L for Use With M7-A6—MIC Testing. . . . 87
Table 1. Suggested Groupings of U.S. FDA-Approved Antimicrobial Agents That Should BeConsidered for Routine Testing and Reporting on Nonfastidious Organisms by Clinical MicrobiologyLaboratories . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 92
Table 1A. Suggested Groupings of U.S. FDA-Approved Antimicrobial Agents That Should BeConsidered for Routine Testing and Reporting on Fastidious Organisms by Clinical MicrobiologyLaboratories . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 98
Table 1B. Suggested Grouping of Antimicrobial Agents That Should Be Considered for Testing andReporting on Potential Agents of Bioterrorism . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 101
Tables 2A-2L. MIC Interpretive Standards (µg/mL) for:
2A. Enterobacteriaceae . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 102
2B. Pseudomonas aeruginosa and Other Non-Enterobacteriaceae . . . . . . . . . . . . . . . . . . . . . . . . . 108
2C. Staphylococcus spp. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 110
2D. Enterococcus spp.. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 116
2E. Haemophilus spp. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 120
2F. Neisseria gonorrhoeae . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 124
2G. Streptococcus pneumoniae . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 126
2H. Streptococcus spp. Other Than Streptococcus pneumoniae. . . . . . . . . . . . . . . . . . . . . . . . . . . . 130
2I. Vibrio cholerae . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 134
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Contents (Continued)2J. Helicobacter pylori . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 135
2K. Bacillus anthracis, Yersinia pestis, Burkholderia mallei, Burkholderia pseudomallei, andFrancisella tularensis. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 136
2L. Neisseria meningitidis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 138
Table 3. Acceptable Limits for Quality Control Strains Used to Monitor Accuracy of MinimalInhibitory Concentrations (MICs) (µg/mL) of Nonfastidious Organisms (Using Cation-AdjustedMueller-Hinton Medium Without Blood or Other Nutritional Supplements) . . . . . . . . . . . . . . . . . . 140
Table 3A. Acceptable Limits for Quality Control Strains Used to Monitor Accuracy of MinimalInhibitory Concentrations (MICs) (µg/mL) of Fastidious Organisms. . . . . . . . . . . . . . . . . . . . . . . . 142
Table 3B. Acceptable Limits for Quality Control Strains Used to Monitor Accuracy of MinimalInhibitory Concentrations (MICs) (µg/mL) Generated in Cation-Adjusted Mueller-Hinton Broth+ 2% Defined Growth Supplement . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 144
Table 3C. Reference Guide to Quality Control Testing Frequency. . . . . . . . . . . . . . . . . . . . . . . . . . 145
Table 4. Solvents and Diluents for Preparation of Stock Solutions of Antimicrobial Agents . . . . . 146
Table 5. Scheme for Preparing Dilutions of Antimicrobial Agents to Be Used in Agar DilutionSusceptibility Tests. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 149
Table 6. Scheme for Preparing Dilutions of Antimicrobial Agents to Be Used in Broth DilutionSusceptibility Tests. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 150
Table 7. Suggested Modifications of Standard Methods for Susceptibility Testing ofListeria spp. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 151
Table 8. Suggestions for Verification of Antimicrobial Susceptibility Test Results andConfirmation of Organism Identification . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 152
Glossary I (Part 1). ß-lactams: Class and Subclass Designation and Generic Name . . . . . . . . . . . 154
Glossary I (Part 2). Non-ß-lactams: Class and Subclass Designation and Generic Name . . . . . . . . 155
Glossary II. Abbreviations/Routes of Administration/Drug Class for Antimicrobial Agents Listedin M100-S15. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 156
List of Identical Abbreviations Used for More Than One Antimicrobial Agent in U.S. DiagnosticProducts . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 159
Summary of Comments and Subcommittee Responses (M7-MIC Testing) . . . . . . . . . . . . . . . . . . . 160
Related CLSI/NCCLS Publications . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 163
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The Clinical and Laboratory Standards Institute consensus process, which is the mechanism for movinga document through two or more levels of review by the healthcare community, is an ongoing process.Users should expect revised editions of any given document. Because rapid changes in technology mayaffect the procedures, methods, and protocols in a standard or guideline, users should replace outdatededitions with the current editions of CLSI/NCCLS documents. Current editions are listed in the CLSIcatalog, which is distributed to member organizations, and to nonmembers on request. If yourorganization is not a member and would like to become one, and to request a copy of the catalog, contactus at: Telephone: +610.688.0100; Fax: +610.688.0700; E-Mail: [email protected]; Website:www.clsi.org.
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Updated Information in This Edition
This document includes all of the tables from the Clinical and Laboratory Standards Institute DiskDiffusion (M2) susceptibility testing and Aerobic Dilution (M7) susceptibility testing documents. Thereare several important changes to the tables that have resulted from meetings of the Subcommittee onAntimicrobial Susceptibility Testing during 2004. Included below is a summary of the changes in thisdocument, which supersede the tables published in 2004 and in earlier years.
Summary of Major Changes in This Document
The list includes the “major” changes in this document. Other minor or editorial changes have been madeto the general formatting and to some of the table footnotes. Boldface type is used to highlight the changesin each table.
Additions/Changes/Deletions
The following are additions or changes unless otherwise noted as a “deletion.”
Clarification of temperature range for incubation in “Testing Conditions” box (M2 and M7; Tables 2A-2K)
Enterobacteriaceae:
ESBL Testing (M2 and M7; Table 2A)Recommendations for testing Proteus mirabilis for ESBL production with slight modification of several screening test breakpoints Escherichia coli ATCC® 25922 for QC of ESBL phenotypic confirmatory test (M7 only) Clarification of QC frequency for ESBL screening and confirmatory tests
Non-Enterobacteriaceae:
Separate lists of antimicrobial agents suggested for testing and reporting for Pseudomonas aeruginosa,Acinetobacter spp., Burkholderia cepacia, and Stenotrophomonas maltophilia (M2 and M7; Table 1).Footnotes j (M2 and M7) and k (M7) were modified accordingly.
Qualification of suggestion that cefotaxime, ceftriaxone, and ceftizoxime be considered for reporting onlyon Pseudomonas spp. (not P. aeruginosa) and other nonfastidious, glucose-nonfermenting, gram-negativebacilli (Test/Report Group C) (M7; Table 1)
Polymyxin B
MIC interpretive criteria which can be used to predict results for colistin also (M7; Table 2B)
Trimethoprim-sulfamethoxazoleDisk diffusion interpretive criteria for B. cepacia (M2; Table 2B)
Staphylococcus spp.:
Clindamycin induction test Suggestions for quality assessment and quality control (M2 and M7; Table 2C and “Minimal QCRecommendations” box)
Daptomycin Test/Report Group B (M2 and M7; Table 1)
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Daptomycin (Continued)
Disk diffusion and MIC interpretive criteria (M2 and M7; Table 2C)Special broth and agar media recommendations for testing daptomycin (M7; Table 2C and “TestingConditions” box)
Flucloxacillin - results can be deducted from testing oxacillin (M7; Table 2C)
Gatifloxacin - revised interpretive criteria (M2 and M7; Table 2C)
Levofloxacin - revised interpretive criteria (M2 and M7; Table 2C)
Moxifloxacin Test/Report Group C (M2 and M7; Table 1)Disk diffusion and MIC interpretive criteria (M2 and M7; Table 2C)
Ofloxacin - revised interpretive criteria (M2 and M7; Table 2C)
TelithromycinTest/Report Group B (M2 and M7; Table 1)Revised Test/Report Group (M2 and M7; Table 2C)
Vancomycin Suggestion for detecting S. aureus strains with reduced susceptibility to vancomycin with reference toBHI vancomycin agar screen test (M2 and M7; Table 2C)
Oxacillin related issues/comments (M2 and M7; Table 2C)Clarification of recommendations for reporting beta-lactam results on oxacillin-susceptiblestaphylococci (M2 and M7; Table 2C)Expanded discussion on use of mecA and PBP 2a testsExpanded discussion on use of cefoxitin disk testStaphylococcus lugdunensis - cefoxitin (disk diffusion) and oxacillin (disk diffusion and MIC) interpretivecriteria for S. aureus should be used for S. lugdunensis
Enterococcus spp.:
Daptomycin Test/Report Group B for vancomycin-susceptible Enterococcus faecalis only (M2 and M7; Table 1)Disk diffusion and MIC interpretive criteria (M2 and M7; Table 2D)Special broth and agar media recommendations for testing daptomycin (M7; Table 2D “TestingConditions” box)
Haemophilus spp.:
TelithromycinTest/Report Group C (M2 and M7; Table 1A)Revised Test/Report Group (M2 and M7; Table 2E)
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Streptococcus pneumoniae:
Fluoroquinolones
Deleted “or” designation and eliminated the ability to use results from testing one fluoroquinolone topredict results for another fluoroquinolone (M2 and M7; Group B, Table 1A and Table 2G)
TelithromycinTest/Report Group B (M2 and M7; Table 1A)Revised Test/Report Group (M2 and M7; Table 2G)
Streptococcus spp. Other Than Streptococcus pneumoniae
Clindamycin Recommendation for detecting inducible clindamycin resistance in beta-hemolytic streptococci (M2 andM7; Table 2H)
Clindamycin and Erythromycin Recommendation for testing Group B streptococci for intrapartum prophylaxis (M2 and M7; Table 2H)
Daptomycin Test/Report Group C (M2 and M7; Table 1A)Disk diffusion and MIC interpretive criteria for beta-hemolytic streptococci only (M2 and M7; Table 2H)Special broth and agar media recommendations for testing daptomycin (M7; Table 2H “TestingConditions” box)
Potential Agents of Bioterrorism:
MIC Table expanded to include recommendations and interpretive criteria for Francisella tularensis(M7; Table 2K)
Neisseria meningitidis:
MIC interpretive standards listed in new table (M7; Table 2L)
QC Range Changes/Additions (Table 3):
Chloramphenicol - Staphylococcus aureus ATCC® 29213 (M7)
Colistin - Escherichia coli ATCC® 25922 (M2 and M7)Pseudomonas aeruginosa ATCC® 27853 (M2 and M7)
Dalbavancin - Staphylococcus aureus ATCC® 29213 (M7)Enterococcus faecalis ATCC® 29212 (M7)
Daptomycin - Enterococcus faecalis ATCC® 29212 (M7)
January 2005 M100-S15
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Updated Information in This Edition (Continued)
Doripenem - Staphylococcus aureus ATCC® 25923 (M2)Staphylococcus aureus ATCC® 29213 (M7)Escherichia coli ATCC® 25922 (M2 and M7)Enterococcus faecalis ATCC® 29212 (M7)Pseudomonas aeruginosa ATCC® 27853 (M2 and M7)
Doxycycline - Staphylococcus aureus ATCC® 29213 (M7)Enterococcus faecalis ATCC® 29212 (M7)
Polymyxin B - Escherichia coli ATCC® 25922 (M2 and M7)Pseudomonas aeruginosa ATCC® 27853 (M2 and M7)
Telavancin - Staphylococcus aureus ATCC® 25923 (M2)Staphylococcus aureus ATCC® 29213 (M7)Enterococcus faecalis ATCC® 29212 (M7)
Tigecycline - Staphylococcus aureus ATCC® 25923 (M2)Staphylococcus aureus ATCC® 29213 (M7) Escherichia coli ATCC® 25922 (M2 and M7)Pseudomonas aeruginosa ATCC® 27853 (M2)Enterococcus faecalis ATCC® 29212 added (M7)
Tigecycline - instructions for using fresh CAMHB for broth microdilution tests
QC Range Changes/Additions (Table 3A):
Dalbavancin - Streptococcus pneumoniae ATCC® 49619 (M7)
Doripenem - Streptococcus pneumoniae ATCC® 49619 (M2 and M7)Haemophilus influenzae ATCC® 49247 (M2 and M7)
Doxycycline - Streptococcus pneumoniae ATCC® 49619 (M7)
Telavancin - Streptococcus pneumoniae ATCC® 49619 (M2 and M7)
Tigecycline - Haemophilus influenzae ATCC® 49247 (M2 and M7)Neisseria gonorrhoeae ATCC® 49226 (M2) Streptococcus pneumoniae ATCC® 49619 (M2 and M7)
QC Ranges for MICs Generated in Cation-Adjusted MHB with Growth Supplement (M7; newTable 3B)
Reference Guide to QC Testing Frequency (M2, Table 3B; M7, Table 3C)
Clarification that recommendations in this table do not eliminate the need for routine weekly or daily QCtesting (M2, Table 3B; M7, Table 3C)
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It is important for users of M2-A8 and M7-A6 to recognize that commercial susceptibility testingdevices are not addressed in these standards. The methods described herein are generic referenceprocedures that can be used for routine susceptibility testing by clinical laboratories, or that canbe used by clinical laboratories to evaluate commercial devices for possible routine use. Resultsgenerated by the CLSI/NCCLS reference methods are used by the United States Food and DrugAdministration to evaluate the performance of commercial systems before clearance is given formarketing in the United States. Clearance by the FDA indicates that the agency concludes thatcommercial devices provide susceptibility results that are substantially equivalent to resultsgenerated using the CLSI/NCCLS reference methods for the organisms and antimicrobial agentsdescribed in the manufacturer’s approved package insert. Some laboratories could find that acommercial dilution, antibiotic gradient, colorimetric, turbidimetric, fluorometric, or othermethod is suitable for selective or routine use.
Updated Information in This Edition (Continued)
Indication that users of FDA-cleared antimicrobial susceptibility test systems should utilize QC limitslisted in the product literature (M7; Table 3C)
Suggestions for Verification of Antimicrobial Susceptibility Test Results and Confirmation ofOrganism Identification (MIC) (M2, Table 4; M7, Table 8)
Daptomycin-NS under Category I for the following organisms: Enterococcus spp.; Enterococcus faecalis;Enterococcus faecium; Staphylococcus aureus; Staphylococcus, coagulase-negative; Streptococcus, betagroup; and Streptococcus, viridans group (M2, Table 4; M7, Table 8)
Suggestion that laboratories report to their public health department Salmonella spp. found to beintermediate or resistant 3rd-generation cephalosporins and/or intermediate or resistant tofluoroquinolones or resistant to nalidixic acid. (M2, Table 4; M7, Table 8)
Suggested Modifications of Standard Methods for Susceptibility Testing:
Deletion:Recommendations for Neisseria meningitidis as standard recommendations of this species are now inTable 2L (M7, Table 7)
Solvents and Diluents for Preparation of Stock Solutions of Antimicrobial Agents
Colistin, Dalbavancin, Daptomycin, Doripenem, Polymyxin B, Telavancin, and Tigecycline (M2, Table 4)
Glossaries I and II
Colistin, Dalbavancin, Doripenem, Oritavancin, Polymyxin B, Telavancin, and Tigecycline added(Glossaries I and II)
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Vol. 25 No. 1 M100-S15
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Subcommittee on Antimicrobial Susceptibility Testing Mission Statement
The Subcommittee on Antimicrobial Susceptibility Testing is composed of representatives from theprofessions, government, and industry, including microbiology laboratories, government agencies,healthcare providers and educators, and pharmaceutical and diagnostic microbiology industries. Usingthe CLSI voluntary consensus process, the subcommittee develops standards that promote accurateantimicrobial susceptibility testing and appropriate reporting.
The mission of the Subcommittee on Antimicrobial Susceptibility Testing is to:
• Develop standard reference methods for antimicrobial susceptibility tests.
• Provide quality control parameters for standard test methods.
• Establish interpretive criteria for the results of standard antimicrobial susceptibility tests.
• Provide suggestions for testing and reporting strategies that are clinically relevant and cost-effective.
• Continually refine standards and optimize the detection of emerging resistance mechanisms through the development of new or revised methods, interpretive criteria, and quality control parameters.
• Educate users through multimedia communication of standards and guidelines.
• Foster a dialogue with users of these methods and those who apply them.
The ultimate purpose of the subcommittee’s mission is to provide useful information to enablelaboratories to assist the clinician in the selection of appropriate antimicrobial therapy for patient care.The standards and guidelines are meant to be comprehensive and to include all antimicrobial agents forwhich the data meet established CLSI/NCCLS guidelines. The values that guide this mission are quality,accuracy, fairness, timeliness, teamwork, consensus, and trust.
January 2005 M100-S15
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For Use With M2-A8–Disk Diffusion M100-S15
©Clinical and Laboratory Standards Institute. All rights reserved. 19
Introduction to Tables 1 Through 1A and 2A Through 2I for Use With M2-A8—Disk Diffusion
I. Selecting Antimicrobial Agents for Testing and Reporting
A. Selection of the most appropriate antimicrobial agents to test and to report is a decision best madeby each clinical laboratory in consultation with the infectious disease practitioners and thepharmacy, as well as the pharmacy and therapeutics and infection control committees of themedical staff. The recommendations here for each organism group comprise agents of provenefficacy that show acceptable in vitro test performance. Considerations in the assignment of agentsto specific test/report groups include clinical efficacy, prevalence of resistance, minimizingemergence of resistance, cost, FDA indications, and current consensus recommendations for first-choice and alternative drugs, in addition to the specific issues described. Tests of selected agentsmay be useful for infection control purposes.
B. The listing of drugs together in a single box designates clusters of comparable agents that need notbe duplicated in testing, because interpretive results are usually similar and clinical efficacycomparable. In addition, an “or” designates a related group of agents that has an almost identicalspectrum of activity and interpretive results, and for which cross-resistance and susceptibility arenearly complete. Therefore, usually only one of the agents within each selection box (cluster orrelated group) need be selected for testing. Agents reported must be tested, unless reporting basedon testing another agent provides a more accurate result (e.g., susceptibility of staphylococci tocefazolin or cephalothin based on oxacillin testing), and they usually should match those includedin the hospital formulary; or else the report should include footnotes indicating the agents thatusually show comparable interpretive results. Unexpected results should be considered forreporting (e.g., resistance of Enterobacteriaceae to third-generation cephalosporins or imipenem).
On the following pages, you will find:
1. Tables 1 and 1A—Suggested groupings of U.S. FDA-approved antimicrobial agentsthat should be considered for routine testing and reporting by clinical microbiologylaboratories.
2. For each organism group, an additional table (Tables 2A through 2I) that contains:a. Recommended testing conditions.b. Minimal QC recommendations. (See also the M2-A8 text document, Section 10.)c. General comments for testing the organism group and specific comments for testing
particular drug/organism combinations.d. Suggested agents that should be considered for routine testing and reporting by
clinical microbiology laboratories as specified in Tables 1 and 1A (test/reportgroups A, B, C, U; the latter for “urine”).
e. Additional drugs that have an approved indication for the respective organismgroup, but would generally not warrant routine testing by a clinical microbiologylaboratory in the United States (test/report group O for “other”; test/report groupInv. for “investigational” [not yet FDA approved]).
f. Zone diameter interpretive criteria and equivalent MIC values which represent MICbreakpoints used in determining approximate zone diameter interpretive criteria.They relate to MICs determined by M7 methodology. Occasional discrepancies mayexist between M2 and M7 due to methodological limitations.
January 2005 Vol. 25 No. 1
©Clinical and Laboratory Standards Institute. All rights reserved.20
C. Test/Report Groups
1. As listed in Tables 1 and 1A, agents in Group A are considered appropriate for inclusionin a routine, primary testing panel, as well as for routine reporting of results for thespecific organism groups.
2. Group B comprises agents that are important clinically, particularly for nosocomialinfections, and they may warrant primary testing. However, they may be reported onlyselectively, such as when the organism is resistant to agents of the same class, as in GroupA. Other indications for reporting the result might include a selected specimen source(e.g., a third-generation cephalosporin for enteric bacilli from cerebrospinal fluid [CSF]or trimethoprim-sulfamethoxazole for urinary tract isolates); a polymicrobial infection;infections involving multiple sites; on request in case of allergy, intolerance, or failure torespond to an agent in Group A; or for reporting to infection control as an epidemiologicaid.
3. Group C comprises alternative or supplemental antimicrobial agents that may requiretesting in those institutions that harbor endemic or epidemic strains resistant to several ofthe primary drugs (especially in the same class, e.g., β-lactams or aminoglycosides); fortreatment of patients allergic to primary drugs; for treatment of unusual organisms (e.g.,chloramphenicol for extraintestinal isolates of Salmonella spp. or some vancomycin-resistant enterococci); or for reporting to infection control as an epidemiologic aid.
4. Group U (“urine”) lists certain antimicrobial agents (e.g., nitrofurantoin and certainquinolones) that are used only or primarily for treating urinary tract infections. Theseagents should not be routinely reported against pathogens recovered from other sites ofinfection. Other agents with broader indications may be included in Group U for specificurinary pathogens (e.g., P. aeruginosa).
5. Group O (“other”) includes agents that have a clinical indication for the organism groupbut are generally not candidates for routine testing and reporting in the United States.
6. Group Inv. (“investigational”) includes agents that are investigational for the organismgroup and have not yet been approved by the FDA.
D. Selective Reporting
Each laboratory should decide which agents in the tables to report routinely (Group A) and whichmight be reported only selectively (from Group B), in consultation with the infectious diseasepractitioners and the pharmacy, as well as the pharmacy and therapeutics and infection controlcommittees of the medical staff of the hospital. Selective reporting should help improve theclinical relevance of test reports and help minimize the selection of multiresistant nosocomialstrains by overuse of broad-spectrum agents. Results for Group B agents not reported routinelyshould be available on request, or they may be reported for selected specimens. Unexpectedresistance, when confirmed, should be reported (e.g., resistance to a secondary agent butsusceptibility to a primary agent).
For Use With M2-A8–Disk Diffusion M100-S15
©Clinical and Laboratory Standards Institute. All rights reserved. 21
II. Reporting Results
Recommended interpretive criteria are based on usual dosage regimens and routes ofadministration in the U.S.
A. Susceptible, intermediate, or resistant interpretations of zone diameter measurements are reportedand defined as follows:
1. Susceptible (S)
The “susceptible” category implies that an infection due to the strain may be appropriatelytreated with the dosage of antimicrobial agent recommended for that type of infection andinfecting species, unless otherwise contraindicated.
2. Intermediate (I)
The “intermediate” category includes isolates with antimicrobial agent MICs thatapproach usually attainable blood and tissue levels and for which response rates may belower than for susceptible isolates. The “intermediate” category implies clinicalapplicability in body sites where the drugs are physiologically concentrated (e.g.,quinolones and ß-lactams in urine) or when a high dosage of a drug can be used (e.g., ß-lactams). The “intermediate” category also includes a “buffer zone” which should preventsmall, uncontrolled technical factors from causing major discrepancies in interpretations,especially for drugs with narrow pharmacotoxicity margins.
3. Resistant (R)
Resistant strains are not inhibited by the usually achievable systemic concentrations of theagent with normal dosage schedules and/or fall in the range where specific microbialresistance mechanisms are likely (e.g., ß-lactamases) and clinical efficacy has not beenreliable in treatment studies.
B. For organisms excluded from Tables 2A through 2I (e.g., Campylobacter spp., Corynebacteriumspp., Bacillus spp.) studies are not yet adequate to develop reproducible, definitive standards tointerpret results. These organisms may require different media, different atmospheres ofincubation, or show marked strain-to-strain variation in growth rate. For these microorganisms,consultation with an infectious disease specialist is recommended for guidance in determining theneed for susceptibility testing and in the interpretation of results. Published reports in the medicalliterature and current consensus recommendations for therapy of uncommon microorganisms mayobviate the need for testing. If necessary, a dilution method usually will be the most appropriatetesting method, and this may require submitting the organism to a reference laboratory. Physiciansshould be informed of the limitations of results and advised to interpret results with caution.
If only “S” criteria are specified:For some organism/antimicrobial combinations, the absence of resistant strains precludesdefining any results categories other than “susceptible.” For strains yielding resultssuggestive of a “nonsusceptible” category, organism identification and antimicrobialsusceptibility test results should be confirmed. Subsequently, the isolates should be savedand submitted to a reference laboratory that will confirm results using a CLSI/NCCLSreference dilution method.
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©Clinical and Laboratory Standards Institute. All rights reserved.22
C. Policies regarding the generation of cumulative antibiograms should be developed in concert withthe infectious disease service, infection control personnel, and the pharmacy and therapeuticscommittee. Under most circumstances, the percentage of susceptible and intermediate resultsshould not be combined into the same statistics.
III. Therapy-Related Comments
Some of the comments in the tables relate to therapy concerns. These are denoted with an Rxsymbol. It may be appropriate to include some of these comments (or modification thereof) on thepatient report. An example would be inclusion of a comment on enterococcus susceptibilityreports from blood cultures that “enterococcal endocarditis requires combined therapy with high-dose penicillin or high-dose ampicillin or vancomycin or teicoplanin plus gentamicin orstreptomycin for bactericidal action.”
Antimicrobial dosage regimens often vary widely among practitioners and institutions. In somecases, the MIC interpretive criteria rely on pharmacokinetic-pharmacodynamic data using specifichuman dosage regimens. In cases where specific dosage regimens are important for properapplication of breakpoints, a therapy-related comment is included.
IV. Verification of Patient Results
Multiple test parameters are monitored by following the quality control recommendationsdescribed in this standard. However, acceptable results derived from testing quality control strainsdo not guarantee accurate results when testing patient isolates. It is important to review all of theresults obtained from all drugs tested on a patient’s isolate prior to reporting the results. Thisshould include but not be limited to ensuring that: 1) the antimicrobial susceptibility results areconsistent with the identification of the isolate; 2) the results from individual agents within aspecific drug class follow established hierarchy of activity rules (e.g., third-generation cephemsare more active than first- or second-generation cephems against Enterobacteriaceae); and 3) theisolate is susceptible to those agents for which resistance has not been documented (e.g.,vancomycin and Streptococcus spp.) and for which only “susceptible” interpretive criteria exist inM100.
Unusual or inconsistent results should be verified by checking for the following: 1) transcriptionerrors; 2) contamination of the test (recheck purity plates, etc.); and 3) previous results on thepatient (e.g., Did the patient have the same isolate with an unusual antibiogram previously?) If areason for the unusual or inconsistent result cannot be ascertained, a repeat of the susceptibilitytest or the identification or both of these is in order. Sometimes it is helpful to use an alternativetest method for the repeat test. A suggested list of results that may require verification is includedin Table 4. Each laboratory must develop its own policies for verification of unusual orinconsistent antimicrobial susceptibility test results. This list should emphasize those results thatare highly likely to impact patient care.
For Use With M2-A8–Disk Diffusion M100-S15
©Clinical and Laboratory Standards Institute. All rights reserved. 23
V. Warning
Some of the comments in the tables relate to dangerously misleading results that can occur whencertain antimicrobial agents are tested and reported as susceptible against specific organisms.These are denoted with the word “Warning.”
“Warning”: The following antimicrobial agent/organism combinations may appear active invitro but are not effective clinically and should not be reported as susceptible.
Location Organism Antimicrobial Agents That Must Notbe Reported as Susceptible
Table 2A Salmonella spp., Shigella spp. 1st- and 2nd-generation cephalosporins,and aminoglycosides
Table 2C oxacillin-resistant Staphylococcus spp. all penems, cephems, and other ß-lactams such as amoxicillin-clavulanicacid, piperacillin-tazobactam, andimipenem
Table 2D Enterococcus spp. aminoglycosides (except highconcentrations), cephalosporins,clindamycin, and trimethoprim-sulfamethoxazole
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Table 1. Suggested Groupings of U.S. FDA-Approved Antimicrobial Agents That Should Be Consideredfor Routine Testing and Reporting on Nonfastidious Organisms by Clinical Microbiology Laboratories
Amikacin Amikacin Azithromycinb or clarithromycinb orerythromycinb
Daptomycins
Linezolid Quinupristin-
dalfopristinrAmoxicillin-clavulanic acid
or ampicillin-sulbactamPiperacillin-tazobactamTicarcillin-clavulanic acid
AztreonamCefoperazone Clindamycinb Vancomycinp
DaptomycinCefamandole or
cefonicid orcefuroxime
Linezolid
Telithromycinb
Cefepime Cefepime Trimethoprim-sulfamethoxazole
CefmetazoleCefoperazoneg
CefotetanCefoxitin
CiprofloxacinLevofloxacin
Vancomycin
Cefotaximeg, h, i orceftizoxime g, i orceftriaxoneg, h, i
ImipenemMeropenem
Ciprofloxacing orlevofloxacing
Tobramycin
ErtapenemImipenem or
meropenemMezlocillin or
piperacillinTicarcillinTrimethoprim-
sulfamethoxazoleg
GR
OU
PB
e
PRIM
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TEST
REP
OR
T SE
LEC
TIVE
LY
Aztreonam Ceftazidime (Both are helpfulindicators of extended-spectrum β-lactamases.) i
Netilmicin Chloramphenicolb Gentamicin(high-levelresistance screen only)
Ciprofloxacin orlevofloxacin orofloxacin
Gatifloxacin ormoxifloxacin
Streptomycin(high-level resistance screen only)Chloramphenicol b, g
Kanamycin Quinupristin-dalfopristinm
Gentamicin Chloramphenicolb
Erythomycinb
Tetracyclinec
Rifampind
(These agents may betested for VRE)
q
Netilmicin
Tetracyclinec Rifampind
Tobramycin Tetracyclinec
GR
OU
PC
f
SUPP
LEM
ENTA
LR
EPO
RT
SELE
CTI
VELY
Enterobacteriaceaeg Pseudomonas aeruginosaj
Staphylococcus spp. Enterococcus spp.n
Ampicillin g Ceftazidime Oxacillinl Penicillino or ampicillinCefazolina
Cephalothina
Gentamicin Penicillinl
Gentamicin Mezlocillin or ticarcillin
Piperacillin
Carbenicillin Carbenicillin Lomefloxacin ornorfloxacin
CiprofloxacinLevofloxacinNorfloxacin
CinoxacinLomefloxacin or
norfloxacin orofloxacin
Lomefloxacin ornorfloxacin orofloxacin
Nitrofurantoin Nitrofurantoin
Gatifloxacin
Loracarbef Sulfisoxazole Tetracyclinec
Nitrofurantoin
SulfisoxazoleTrimethoprim Trimethoprim
GR
OU
PU
SU
PPLE
MEN
TAL
FOR
UR
INE
ON
LY
©Clinical and Laboratory Standards Institute. All rights reserved.
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OU
PA
PRIM
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AN
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EPO
RT
For Use With M2-A8–Disk Diffusion M100-S15Table 1. (Continued)
Acinetobacter spp.j,k
Burkholderia cepaciaj,k
Stenotrophomonas maltophiliaj,k
Ceftazidime Trimethoprim-sulfamethoxazole
Trimethoprim-sulfamethoxazole
ImipenemMeropenem
GR
OU
PB
e
PRIM
ARY
TEST
REP
OR
T SE
LEC
TIVE
LY
AmikacinGentamicinTobramycin
Ceftazidime Levofloxacin
Meropenem Minocycline
Minocycline
Ampicillin-sulbactamPiperacillin-tazobactamTicarcillin-clavulanate
Cefepime
CefotaximeCeftriaxone
CiprofloxacinGatifloxacinLevofloxacin
DoxycyclineMinocyclineTetracycline
MezlocillinPiperacillinTicarcillin
Trimethoprim-sulfamethoxazole
GR
OU
PU
SU
PPLE
MEN
TAL
FOR
UR
INE
ON
LY
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dN
onfa
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upin
gsM
2-D
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Diff
usio
n
©Clinical and Laboratory Standards Institute. All rights reserved. 25
GR
OU
PC
f
SUPP
LEM
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LR
EPO
RT
SELE
CTI
VELY
GR
OU
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PRIM
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TEST
AN
D R
EPO
RT
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©Clinical and Laboratory Standards Institute. All rights reserved.26
Table 1. (Continued)
NOTE 1: Selection of the most appropriate antimicrobial agents to test and to report is a decision madebest by each clinical laboratory in consultation with the infectious disease practitioners and thepharmacy, as well as the pharmacy and therapeutics and infection control committees of themedical staff. The lists for each organism group comprise agents of proven efficacy that showacceptable in vitro test performance. Considerations in the assignment of agents to Groups A, B,C, and U include clinical efficacy, prevalence of resistance, minimizing emergence of resistance,cost, and current consensus recommendations for first-choice and alternative drugs, in addition tothe specific comments in footnotes ”e” and “f.” Tests on selected agents may be useful for infectioncontrol purposes.
NOTE 2: The boxes in the table designate clusters of comparable agents that need not be duplicatedin testing, because interpretive results are usually similar and clinical efficacy is comparable. Inaddition, an “or” designates a related group of agents that has an almost identical spectrum ofactivity and interpretive results, and for which cross-resistance and susceptibility are nearlycomplete. Therefore, usually only one of the agents within each selection box (cluster or relatedgroup) need be selected for testing. Agents that are reported must be tested, unless reportingbased on testing another agent provides a more accurate result (e.g., susceptibility of staphylococcito cefazolin or cephalothin based on oxacillin testing), and they should match those included in thehospital formulary; or else the report should include footnotes indicating the agents that usuallyshow comparable interpretive results. Unexpected results should be considered for reporting (e.g.,resistance of Enterobacteriaceae to third-generation cephalosporins or imipenem).
NOTE 3: Information in boldface type is considered tentative for one year.
FootnotesGeneral Comments
a. Cephalothin can be used to represent cephalothin, cephapirin, cephradine, cephalexin, cefaclor, andcefadroxil. Cefazolin, cefuroxime, cefpodoxime, cefprozil, and loracarbef (urinary isolates only) may betested individually, because some isolates may be susceptible to these agents when resistant tocephalothin.
b. Not routinely reported on organisms isolated from the urinary tract.
c. Organisms that are susceptible to tetracycline are also considered susceptible to doxycycline andminocycline. However, some organisms that are intermediate or resistant to tetracycline may besusceptible to doxycycline or minocycline or both.
d. Rx: Rifampin should not be used alone for chemotherapy.
e. Group B represents agents that may warrant primary testing but which should be reported onlyselectively, such as when the organism is resistant to agents of the same class in Group A. Otherindications for reporting the result might include selected specimen sources (e.g., third-generationcephalosporin for isolates of enteric bacteria from cerebrospinal fluid or trimethoprim-sulfamethoxazolefor urinary tract isolates); stated allergy or intolerance, or failure to respond to an agent in Group A;polymicrobial infections; infections involving multiple sites with different microorganisms; or reports toinfection control as an epidemiologic aid.
“Warning”: The following antimicrobial agents should not be routinely reported forbacteria isolated from the CSF and which are included in this document. Theseantimicrobial agents are not the drugs of choice and may not be effective for treating CSFinfections caused by these organisms (i.e., the bacteria included in Tables 2A to 2I):
agents administered by oral route only1st- and 2nd-generation cephalosporins (except cefuroxime sodium)
clindamycinmacrolides
tetracyclinesfluoroquinolones
Tabl
e 1
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dN
onfa
stid
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upin
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2-D
isk
Diff
usio
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For Use With M2-A8–Disk Diffusion M100-S15
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Tabl
e 1
Sugg
este
dN
onfa
stid
ious
Gro
upin
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©Clinical and Laboratory Standards Institute. All rights reserved.
Table 1. (Continued)
f. Group C represents alternative or supplemental antimicrobial agents that may require testing in thoseinstitutions that harbor endemic or epidemic strains resistant to one or more of the primary drugs(especially in the same class, e.g., β-lactams or aminoglycosides), or for treatment of unusual organisms(e.g., chloramphenicol for some Pseudomonas spp., and chloramphenicol, erythromycin, rifampin, andtetracycline for some vancomycin-resistant enterococci), or reporting to infection control as anepidemiologic aid.
Enterobacteriaceae
g. For fecal isolates of Salmonella and Shigella spp., only ampicillin, a quinolone, and trimethoprim-sulfamethoxazole should be tested and reported routinely. In addition, chloramphenicol and a third-generation cephalosporin should be tested and reported for extraintestinal isolates of Salmonella spp.
h. Cefotaxime and ceftriaxone should be tested and reported on isolates from CSF in place of cephalothinand cefazolin.
i. Strains of Klebsiella spp. and E. coli that produce ESBLs may be clinically resistant to therapy withpenicillins, cephalosporins, or aztreonam, despite apparent in vitro susceptibility to some of these agents.Some of these strains will show zones of inhibition below the normal susceptible population but above thestandard breakpoints for certain extended-spectrum cephalosporins or aztreonam; such strains may bescreened for potential ESBL production by using the screening breakpoints listed in the table at the endof Table 2A, Initial Screen Test. Other strains may test intermediate or resistant by standard breakpointsto one or more of these agents. In all strains with ESBLs, the zone diameters for one or more of theextended-spectrum cephalosporins should increase in the presence of clavulanic acid as described at theend of Table 2A, Phenotypic Confirmatory Test. For all confirmed ESBL-producing strains, the testinterpretation should be reported as resistant for all penicillins, cephalosporins, and aztreonam. (SeeGlossary I for specific agents included in the antimicrobial class, penicillins, and antimicrobial subclass,cephalosporins.)
Pseudomonas aeruginosa, Acinetobacter spp., Burkholderia cepacia, and Stenotrophomonasmaltophilia
j. Non-Enterobacteriaceae except for P. aeruginosa, Acinetobacter spp., B. cepacia, and S. maltophiliashould be tested by the dilution method (see M7).
k. Other agents may be approved for therapy but their performance has not been sufficientlystudied to establish disk diffusion breakpoints.
Staphylococcus spp.
l. Penicillin-susceptible staphylococci are also susceptible to other penicillins, cephems, and carbapenemsapproved for use by the FDA for staphylococcal infections. Penicillin-resistant, oxacillin-susceptible strainsare resistant to penicillinase-labile penicillins but susceptible to other penicillinase-stable penicillins, β-lactam/β-lactamase inhibitor combinations, relevant cephems, and carbapenems. (See Glossary I forspecific agents included in the antimicrobial class or antimicrobial subclass indicated). Oxacillin-resistantstaphylococci are resistant to all currently available β-lactam antibiotics. Thus, susceptibility or resistanceto a wide array of β-lactam antibiotics may be deduced from testing only penicillin and oxacillin. Routinetesting of other penicillins, β-lactamase inhibitor combinations, cephems, and carbapenems is notadvised.
m.For reporting against methicillin-susceptible Staphylococcus aureus.
Enterococcus spp.
n. Warning: For Enterococcus spp., cephalosporins, aminoglycosides (except for high-level resistancescreening), clindamycin, and trimethoprim-sulfamethoxazole may appear active in vitro but are noteffective clinically, and isolates should not be reported as susceptible.
o. Penicillin susceptibility may be used to predict the susceptibility to ampicillin, amoxicillin, ampicillin-
January 2005 Vol. 25 No. 1
28
Tabl
e 1
Sugg
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dN
onfa
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gsM
2-D
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Diff
usio
n
©Clinical and Laboratory Standards Institute. All rights reserved.
sulbactam, amoxicillin-clavulanic acid, piperacillin, and piperacillin-tazobactam for non-β-lactamase-producing enterococci. For blood and cerebrospinal fluid isolates, a β-lactamase test is alsorecommended. Rx: Combination therapy of penicillin or ampicillin, plus an aminoglycoside, is usuallyindicated for serious enterococcal infections, such as endocarditis.
p. Rx: If vancomycin is used for serious enterococcal infections, such as endocarditis, combined therapy withan aminoglycoside is usually indicated.
q. Because of limited alternatives, chloramphenicol, erythromycin, tetracycline (or doxycycline orminocycline), and rifampin may be tested for vancomycin-resistant enterococci (VRE), and consultationwith an infectious disease practitioner is recommended.
r. For reporting against vancomycin-resistant Enterococcus faecium.
s. For reporting against vancomycin-susceptible Enterococcus faecalis.
Table 1. (Continued)
For Use With M2-A8–Disk Diffusion M100-S15
29©Clinical and Laboratory Standards Institute. All rights reserved.
This page is intentionally left blank.
30
Tabl
e 1A
Sugg
este
dFa
stid
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Gro
upin
gsM
2-D
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Diff
usio
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©Clinical and Laboratory Standards Institute. All rights reserved.
January 2005 Vol. 25 No. 1
Table 1A. Suggested Groupings of U.S. FDA-Approved Antimicrobial Agents That Should Be Consideredfor Routine Testing and Reporting on Fastidious Organisms by Clinical Microbiology Laboratories
GR
OU
PA
PRIM
ARY
TEST
A
ND
REP
OR
THaemophilus spp.e Neisseria
gonorrhoeaeStreptococcus pneumoniae j
Streptococcus spp.Other ThanStreptococcus pneumoniae
Ampicillin e, g Erythromycina Erythromycina,o,r
Trimethoprim-sulfamethoxazole
Penicillin (oxacillin disk)k Penicillinm, n, p or ampicillinn, p
Trimethoprim-sulfamethoxazole
Azithromycinf orclarithromycinf
Cefixime orcefotaxime orcefpodoxime orceftizoxime orceftriaxone
ChloramphenicoloCefepime or
cefotaxime orceftriaxone
Aztreonam Linezolid
Cefaclorf or cefprozilf orloracarbef f
CefmetazoleCefotetanCefoxitinCefuroxime
Rifampinl Daptomycinn
Levofloxacinn
Ofloxacinn
Cefdinirf orcefiximef orcefpodoximef
Linezolid
Cefonicid
Cefuroxime axetilf (oral) Ciprofloxacin orgatifloxacin or ofloxacin
Quinupristin-dalfopristinq
Ciprofloxacin orgatifloxacin orlevofloxacin or lomefloxacin ormoxifloxacin orofloxacin orsparfloxacin
Gemifloxacin
Penicillini
Ertapenem orimipenem
Spectinomycin
TetracyclineRifampin
Telithromycinf
Tetracyclined
GR
OU
PC
c
SUPP
LEM
ENTA
LR
EPO
RT
SELE
CTI
VELY
Cefotaximee orceftazidimee orceftizoximee orceftriaxonee
Clindamycin Chloramphenicolo
Gatifloxacin GemifloxacinLevofloxacinMoxifloxacinOfloxacinSparfloxacin
Cefuroxime sodium(parenteral)
Telithromycin
Tetracyclined
Chloramphenicole
Meropeneme,h Vancomycink
Clindamycino,r
Vancomycin
GR
OU
PB
b
PRIM
ARY
TEST
R
EPO
RT
SELE
CTI
VELY
For Use With M2-A8–Disk Diffusion M100-S15
31
Tabl
e 1A
Sugg
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dFa
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Gro
upin
gsM
2-D
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Diff
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©Clinical and Laboratory Standards Institute. All rights reserved.
Table 1A. (Continued)
NOTE 1: Selection of the most appropriate antimicrobial agents to test and to report is a decision bestmade by each clinical laboratory in consultation with the infectious disease practitioners and thepharmacy, as well as the pharmacy and therapeutics and infection control committees of themedical staff. The lists for each organism group comprise agents of proven efficacy that showacceptable in vitro test performance. Considerations in the assignment of agents to Groups A, B,and C include clinical efficacy, prevalence of resistance, minimizing emergence of resistance, cost,and current consensus recommendations for first-choice and alternative drugs, in addition to thespecific comments in footnotes “b” and “c.” Tests on selected agents may be useful for infectioncontrol purposes.
NOTE 2: The boxes in the table designate clusters of comparable agents that need not be duplicated intesting, because interpretive results are usually similar and clinical efficacy is comparable. Inaddition, an “or” designates a related group of agents that has an almost identical spectrum ofactivity and interpretive results, and for which cross-resistance and susceptibility are nearlycomplete. Therefore, usually only one of the agents within each selection box (cluster or relatedgroup) need be selected for testing. Agents reported must be tested, unless reporting based ontesting another agent provides a more accurate result, and they should match those included in thehospital formulary; or else the report should include footnotes indicating the agents that usuallyhave comparable interpretive results. Unexpected results should be considered for reporting.
NOTE 3: Information in boldface type is considered tentative for one year.
Footnotes
General Comments
a. Susceptibility and resistance to azithromycin, clarithromycin, and dirithromycin can be predicted bytesting erythromycin.
b. Group B represents agents that may warrant primary testing but which should be reported onlyselectively, such as when the organism is resistant to agents of the same class in Group A. Otherindications for reporting the result might include selected specimen sources (e.g., third-generationcephalosporin for isolates of Haemophilus influenzae from CSF); stated allergy or intolerance, orfailure to respond to an agent in Group A; polymicrobial infections; infections involving multiple siteswith different microorganisms; or reports to infection control as an epidemiologic aid.
c. Group C represents alternative or supplemental antimicrobial agents that may require testing in thoseinstitutions that harbor endemic or epidemic strains resistant to one or more of the primary drugs(especially in the same class, e.g., β-lactams), or for treatment of unusual organisms, or reporting toinfection control as an epidemiologic aid.
“Warning”: The following antimicrobial agents should not be routinely reported forbacteria isolated from the CSF and which are included in this document. Theseantimicrobial agents are not the drugs of choice and may not be effective for treatingCSF infections caused by these organisms (i.e., the bacteria included in Tables 2A to2I):
agents administered by oral route only1st- and 2nd-generation cephalosporins (except cefuroxime sodium)
clindamycinmacrolides
tetracyclinesfluoroquinolones
January 2005 Vol. 25 No. 1
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©Clinical and Laboratory Standards Institute. All rights reserved.
Table 1A. (Continued)
d. Organisms that are susceptible to tetracycline are also considered susceptible to doxycycline andminocycline.
Haemophilus spp.
e. Only results of testing with ampicillin, one of the third-generation cephalosporins, chloramphenicol,and meropenem should be reported routinely with CSF isolates of H. influenzae.
f. Amoxicillin-clavulanic acid, azithromycin, clarithromycin, cefaclor, cefprozil, loracarbef, cefdinir,cefixime, cefpodoxime, cefuroxime axetil, and telithromycin are oral agents that may be used asempiric therapy for respiratory tract infections due to Haemophilus spp. The results of susceptibilitytests with these antimicrobial agents are often not useful for management of individual patients.However, susceptibility testing of Haemophilus spp. with these compounds may be appropriate forsurveillance or epidemiologic studies.
g. The results of ampicillin susceptibility tests should be used to predict the activity of amoxicillin. Themajority of isolates of H. influenzae that are resistant to ampicillin and amoxicillin produce a TEM-typeβ-lactamase. In most cases, a direct β-lactamase test can provide a rapid means of detectingampicillin and amoxicillin resistance.
h. Clinical indications and relevant pathogens include bacterial meningitis and concurrent bacteremia inassociation with meningitis caused by H. influenzae (β-lactamase and non-β-lactamase-producingstrains).
Neisseria gonorrhoeae
i. A β-lactamase test will detect one form of penicillin resistance in N. gonorrhoeae and also may be usedto provide epidemiologic information. Strains with chromosomally mediated resistance can bedetected only by additional susceptibility testing, such as the disk diffusion method or the agar dilutionMIC method.
Streptococcus pneumoniae
j. Amoxicillin, ampicillin, cefepime, cefotaxime, ceftriaxone, cefuroxime, imipenem, and meropenem maybe used to treat pneumococcal infections; however, reliable disk diffusion susceptibility tests withthese agents do not yet exist. Their in vitro activity is best determined using an MIC method (see M7).
k. Penicillin, cefotaxime or ceftriaxone, and meropenem should be tested by a reliable MIC method (suchas that described in CLSI/NCCLS document M7) and reported routinely with CSF isolates of S.pneumoniae. Such isolates should also be tested against vancomycin using the MIC or disk method.With isolates from other sites, the oxacillin disk screening test may be used. If the oxacillin zone sizeis ≤ 19 mm, penicillin and cefotaxime or ceftriaxone MICs should be determined.
l. Rx: Rifampin should not be used alone for chemotherapy.
Streptococcus spp.
m. Viridans streptococci isolated from blood and normally sterile body sites (e.g., cerebrospinal fluid,blood, bone) should be tested for penicillin or ampicillin susceptibility using an MIC method.
n. Disk diffusion interpretive criteria for penicillin, ampicillin, levofloxacin, ofloxacin, and daptomycin arefor reporting against isolates of beta-hemolytic streptococci only.
For Use With M2-A8–Disk Diffusion M100-S15
33
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gsM
2-D
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Diff
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©Clinical and Laboratory Standards Institute. All rights reserved.
Table 1A. (Continued)
o. Not routinely reported on organisms isolated from the urinary tract.
p. Susceptibility testing of penicillins and other β-lactams approved by FDA for treatment ofStreptococcus pyogenes or Streptococcus agalactiae is not necessary for clinical purposes and neednot be done routinely, since as with vancomycin, resistant strains have not been recognized.Interpretive criteria are provided for pharmaceutical development, epidemiology, or monitoring foremerging resistance. Any strain found to be nonsusceptible should be referred to a referencelaboratory for confirmation.
q. Report against S. pyogenes.
r. Rx: Recommendations for intrapartum prophylaxis for Group B streptococci are penicillin orampicillin. While cefazolin is recommended for penicillin-allergic women at low risk foranaphylaxis, those at high risk for anaphylaxis may receive clindamycin or erythromycin.Group B streptococci are susceptible to ampicillin, penicillin, and cefazolin, but may beresistant to clindamycin and/or erythromycin. When a Group B streptococcus is isolated froma pregnant woman with severe penicillin allergy (high risk for anaphylaxis), clindamycin anderythromycin should be tested and reported.
Min
imal
QC
Rec
omm
enda
tions
(See
Tab
le 3
for a
ccep
tabl
e Q
C ra
nges
.)
Esch
eric
hia
coli
ATC
C®
2592
2Es
cher
ichi
a co
liAT
CC
®35
218
(for β
-lact
am/β
-lact
amas
e in
hibi
tor
com
bina
tions
)
January 2005 Vol. 25 No. 1
34
Tabl
e 2A
Ente
roba
cter
iace
aeM
2-D
isk
Diff
usio
n
©Clinical and Laboratory Standards Institute. All rights reserved.
Tabl
e 2A
. Zo
ne D
iam
eter
Inte
rpre
tive
Stan
dard
s an
d Eq
uiva
lent
Min
imal
Inhi
bito
ry C
once
ntra
tion
(MIC
) Bre
akpo
ints
for
Ente
roba
cter
iace
ae
Gen
eral
Com
men
ts
(1)
For
feca
l iso
late
s of
Sal
mon
ella
and
Shig
ella
spp.
onl
y am
pici
llin,
a q
uino
lone
, and
trim
etho
prim
-sul
fam
etho
xazo
le s
houl
d be
test
ed a
nd re
porte
d ro
utin
ely.
Inad
ditio
n, c
hlor
amph
enic
ol a
nd a
third
-gen
erat
ion
ceph
alos
porin
sho
uld
be te
sted
and
repo
rted
for e
xtra
inte
stin
al is
olat
es o
f Sal
mon
ella
spp.
NO
TE:I
nfor
mat
ion
in b
oldf
ace
type
is c
onsi
dere
d te
ntat
ive
for o
ne y
ear.
Test
/Rep
ort
Gro
up
Ant
imic
robi
al A
gent
Dis
k C
onte
ntZo
ne D
iam
eter
, N
eare
st W
hole
mm
Equi
vale
nt M
IC
Bre
akpo
ints
(µµg/
mL)
C
omm
ents
RI
SR
S
PEN
ICIL
LIN
SA
Am
pici
llin
10 µ
g≤
13
14-1
6 ≥
17
≥32
≤
8 (2
) C
lass
repr
esen
tativ
e fo
ram
pici
llin
and
amox
icill
in.
B B B
Mez
loci
llin
or
pipe
raci
llin
Tica
rcill
in
75 µ
g10
0 µg
75 µ
g
≤17
≤17
≤14
18-2
018
-20
15-1
9
≥21
≥21
≥20
≥12
8≥
128
≥12
8
≤16
≤16
≤16
UC
arbe
nici
llin
100
µg≤
1920
-22
≥23
≥64
≤16
UM
ecill
inam
10
µg
≤11
12-1
4 ≥
15
≥32
≤
8 (3
) Fo
r use
aga
inst
E. c
oli u
rinar
ytra
ct is
olat
es o
nly.
ββ -
LAC
TAM
/ββ-L
AC
TAM
ASE
INH
IBIT
OR
CO
MB
INAT
ION
SB B B B
Am
oxic
illin
-cla
vula
nic
acid
or
ampi
cilli
n-su
lbac
tam
Pip
erac
illin
-tazo
bact
amTi
carc
illin
-cla
vula
nic
acid
20/1
0 µg
10/1
0 µg
100/
10 µ
g75
/10
µg
≤13
≤11
≤17
≤14
14-1
712
-14
18-2
015
-19
≥18
≥15
≥21
≥20
≥32
/16
≥32
/16
≥12
8/4
≥12
8/2
≤8/
4≤
8/4
≤16
/4≤
16/2
Test
ing
Con
ditio
ns
Med
ium
:M
uelle
r-H
into
n ag
ar
Inoc
ulum
:G
row
th m
etho
d or
dire
ct c
olon
y su
spen
sion
, eq
uiva
lent
to a
0.5
McF
arla
nd s
tand
ard
Incu
batio
n:35
° C ±
2 de
gree
s; a
mbi
ent a
ir; 1
6 to
18
hour
s
For Use With M2-A8–Disk Diffusion M100-S15
35©Clinical and Laboratory Standards Institute. All rights reserved.
Tabl
e 2A
. (C
ontin
ued)
Test
/Rep
ort
Gro
up
Ant
imic
robi
al
Age
nt
Dis
k C
onte
nt
Zone
Dia
met
er,
Nea
rest
Who
le m
m
Equi
vale
nt M
ICB
reak
poin
ts (µµ
g/m
L)
Com
men
tsR
I
S R
S
CEP
HEM
S (P
AR
ENTE
RA
L) (
Incl
udin
g ce
phal
ospo
rins
I, II,
III,
and
IV. P
leas
e re
fer
to G
loss
ary
I.)
(4)
WA
RN
ING
:For
Sal
mon
ella
spp.
and
Shi
gella
spp.
, firs
t- an
d se
cond
-ge
nera
tion
ceph
alos
porin
s m
ay a
ppea
r act
ive
in v
itro
but a
re n
ot e
ffect
ive
clin
ical
ly a
nd s
houl
d no
t be
repo
rted
as s
usce
ptib
le.
(5)
Stra
ins
of K
lebs
iella
spp
. and
E. c
olit
hat p
rodu
ce e
xten
ded-
spec
trum
beta
-lact
amas
e (E
SB
Ls)
may
be
cl
inic
ally
re
sist
ant
to
ther
apy
with
peni
cilli
ns,
ceph
alos
porin
s,
or
aztre
onam
, de
spite
ap
pare
nt
in
vitro
susc
eptib
ility
to
som
e of
the
se a
gent
s. S
ome
of t
hese
stra
ins
will
sho
wzo
nes
of in
hibi
tion
belo
w th
e no
rmal
sus
cept
ible
pop
ulat
ion
but a
bove
the
stan
dard
bre
akpo
ints
for
cer
tain
ext
ende
d-sp
ectru
m c
epha
losp
orin
s or
aztre
onam
. S
uch
stra
ins
shou
ld
be
scre
ened
fo
r po
tent
ial
ES
BL
prod
uctio
n by
usi
ng th
e E
SB
Lsc
reen
ing
brea
kpoi
nts
liste
d at
the
end
ofth
is
tabl
e be
fore
re
porti
ng
resu
lts
for
peni
cilli
ns,
exte
nded
-spe
ctru
mce
phal
ospo
rins,
or
aztre
onam
. O
ther
stra
ins
may
tes
t in
term
edia
te o
rre
sist
ant b
y st
anda
rd b
reak
poin
ts to
one
or
mor
e of
thes
e ag
ents
. In
all
stra
ins
with
ES
BLs
, the
zon
e di
amet
ers
for o
ne o
r mor
e of
the
exte
nded
-sp
ectru
m c
epha
losp
orin
s or
azt
reon
am s
houl
d in
crea
se in
the
pres
ence
of
clav
ulan
ic a
cid
as d
eter
min
ed in
phe
noty
pic
conf
irmat
ory
test
ing.
Fo
r al
lco
nfirm
ed
ES
BL-
prod
ucin
g st
rain
s,
the
test
in
terp
reta
tion
shou
ld
bere
porte
d as
res
ista
nt f
or a
ll pe
nici
llins
, ce
phal
ospo
rins,
and
azt
reon
am.
(See
tab
le l
ocat
ed a
t th
e en
d of
thi
s ta
ble
for
ES
BL
scre
enin
g an
dco
nfirm
ator
y te
sts.
R
efer
to
glos
sary
for
def
initi
ons
of p
enic
illin
s an
dce
phal
ospo
rins.
) Th
e de
cisi
on t
o pe
rform
ES
BL
scre
enin
g te
sts
on a
llur
ine
isol
ates
sho
uld
be m
ade
on a
n in
stitu
tiona
l ba
sis,
con
side
ring
prev
alen
ce, t
hera
py, a
nd in
fect
ion
cont
rol i
ssue
s.
(6) R
outin
e sc
reen
ing
ofPr
oteu
s m
irabi
lisfo
r ESB
Lpr
oduc
tion
is n
otre
com
men
ded.
How
ever
, whe
n it
is d
eem
ed c
linic
ally
rele
vant
(e.g
., a
bact
erem
ic i
sola
te),
the
ESB
Lsc
reen
tes
ting
zone
s, c
efta
zidi
me
(≤≤22
mm
), ce
fota
xim
e (≤≤
27 m
m),
or c
efpo
doxi
me
(≤≤17
mm
) w
illid
entif
y pr
esum
ptiv
e ES
BL
prod
uctio
n. T
he p
heno
typi
c co
nfirm
ator
yte
st u
sing
cef
tazi
dim
e an
d ce
fota
xim
e al
one
and
in c
ombi
natio
n w
ithcl
avul
anic
ac
id
can
conf
irm
ES
BL-
prod
ucin
g st
rain
s.
For
all
conf
irm
ed
ESB
L-pr
oduc
ing
P.m
irabi
lis,
the
test
in
terp
reta
tion
shou
ld b
e re
port
ed a
s re
sist
ant
for
all
peni
cilli
ns,
ceph
alos
porin
s,an
d az
treo
nam
.
(7)
Ente
roba
cter
, Citr
obac
ter,
and
Serra
tiam
ay d
evel
op re
sist
ance
dur
ing
prol
onge
d th
erap
y w
ith
third
-gen
erat
ion
ceph
alos
porin
s.
Ther
efor
e,is
olat
es th
at a
re in
itial
ly s
usce
ptib
le m
ay b
ecom
e re
sist
ant w
ithin
thre
e to
four
day
s af
ter
initi
atio
n of
the
rapy
. Te
stin
g of
rep
eat
isol
ates
may
be
war
rant
ed.
A AC
efaz
olin
Cep
halo
thin
30
µg
30 µ
g≤
14≤
14
15-1
7 15
-17
≥18
≥
18
≥32
≥32
≤8
≤8
(8) C
epha
loth
in c
an b
e us
ed to
pre
dict
act
ivity
of c
epha
loth
in, c
epha
pirin
,ce
phra
dine
, ce
phal
exin
, ce
facl
or,
and
cefa
drox
il. C
efaz
olin
, ce
furo
xim
e,ce
fpod
oxim
e, c
efpr
ozil,
and
lor
acar
bef
(urin
ary
isol
ates
onl
y) m
ay b
ete
sted
indi
vidu
ally,
bec
ause
som
e is
olat
es m
ay b
e su
scep
tible
to
thes
eag
ents
whe
n re
sist
ant t
o ce
phal
othi
n.
T abl
e 2A
Ente
roba
cter
iace
aeM
2-D
isk
Diff
usio
n
January 2005 Vol. 25 No. 1
36
Tabl
e 2A
Ente
roba
cter
iace
aeM
2-D
isk
Diff
usio
n
©Clinical and Laboratory Standards Institute. All rights reserved.
Tabl
e 2A
. (C
ontin
ued)
Test
/Rep
ort
Gro
up
Ant
imic
robi
al
Age
nt
Dis
k C
onte
nt
Zone
Dia
met
er,
Nea
rest
Who
le m
m
Equi
vale
nt M
ICB
reak
poin
ts (µµ
g/m
L)
Com
men
ts
R
I S
R
S C
EPH
EMS
(PA
REN
TER
AL)
(Con
tinue
d)B B B
Cef
aman
dole
or
cefo
nici
d or
cefu
roxi
me
sodi
um(p
aren
tera
l)
30 µ
g30
µg
30 µ
g
≤ 14
≤
14
≤ 14
15-1
715
-17
15-1
7
≥ 18
≥ 18
≥ 18
≥ 32
≥ 32
≥ 32
≤ 8
≤ 8
≤ 8
BC
efep
ime
30 µ
g≤
1415
-17
≥ 18
≥ 32
≤ 8
B B B B
Cef
met
azol
eC
efop
eraz
one
Cef
otet
anC
efox
itin
30 µ
g75
µg
30 µ
g30
µg
≤12
≤15
≤12
≤14
13-1
516
-20
13-1
515
-17
≥ 16
≥ 21
≥ 16
≥ 18
≥ 6
4≥
64
≥ 6
4≥
32
≤ 16
≤ 16
≤ 16
≤ 8
B B B
Cef
otax
ime
orce
ftizo
xim
e or
ceftr
iaxo
ne
30 µ
g30
µg
30 µ
g
≤ 14
≤
14≤
13
15-2
215
-19
14-2
0
≥ 23
≥ 20
≥ 21
≥ 6
4≥
32
≥ 6
4
≤ 8
≤ 8
≤ 8
(9) C
efot
axim
e an
d ce
ftria
xone
sho
uld
be te
sted
and
repo
rted
on is
olat
es fr
om C
SF
in p
lace
of c
epha
loth
in a
nd c
efaz
olin
.
See
com
men
t (5)
.C
Cef
tazi
dim
e30
µg
≤ 14
15-1
7 ≥
18
≥ 3
2≤
8S
ee c
omm
ent (
5).
OM
oxal
acta
m30
µg
≤ 14
15
-22
≥ 23
≥ 6
4≤
8C
EPH
EMS
(OR
AL)
BC
efur
oxim
e ax
etil
(ora
l)30
µg
≤ 14
15
-22
≥ 23
≥ 3
2≤
4U
Lora
carb
ef30
µg
≤ 14
15
-17
≥ 18
≥ 3
2≤
8(1
0) B
ecau
se c
erta
in s
train
s of
Citr
obac
ter,
Prov
iden
cia,
and
Ente
roba
cter
spp.
hav
e be
en re
porte
d to
giv
e fa
lse-
susc
eptib
lere
sults
with
cef
dini
r an
d lo
raca
rbef
dis
ks,
stra
ins
of t
hese
gene
ra s
houl
d no
t be
test
ed a
nd re
porte
d w
ith th
ese
disk
s.
OC
efac
lor
30 µ
g ≤
14
15-1
7≥
18≥
32≤
8
OC
efdi
nir
5 µg
≤
16
17-1
9≥
20≥
4≤
1S
ee c
omm
ent (
10).
OC
efix
ime
5 µg
≤
1516
-18
≥ 19
≥ 4
≤
1(1
1) N
ot a
pplic
able
for t
estin
g M
orga
nella
spp.
OC
efpo
doxi
me
10 µ
g ≤
1718
-20
≥ 21
≥ 8
≤
2S
ee c
omm
ents
(5) a
nd (1
1).
OC
efpr
ozil
30 µ
g ≤
1415
-17
≥ 18
≥ 3
2≤
8(1
2) B
ecau
se c
erta
in s
train
s of
Pro
vide
ncia
spp.
hav
e be
enre
porte
d to
giv
e fa
lse-
susc
eptia
ble
resu
lts w
ith c
efpr
oxil
disk
s,st
rain
s of
this
gen
us s
houl
d no
t be
test
ed a
nd re
porte
d w
ith th
isdi
sk.
Inv.
Cef
etam
et10
µg
≤ 14
15-1
7≥
18≥
16≤
4S
ee c
omm
ent (
11).
Inv.
Cef
tibut
en30
µg
≤ 17
18-2
0≥
21≥
32≤
8(1
3) In
dica
ted
for u
rine
isol
ates
onl
y.C
AR
BA
PEN
EMS
B B B
Erta
pene
mIm
ipen
em o
rm
erop
enem
10 µ
g 10
µg
10 µ
g
≤ 15
≤ 1
3 ≤
13
16-1
814
-15
14-1
5
≥ 19
≥ 16
≥ 16
≥ 8
≥ 16
≥ 16
≤ 2
≤ 4
≤ 4
MO
NO
BA
CTA
MS
CA
ztre
onam
30 µ
g ≤
15
16-2
1≥
22≥
32≤
8S
ee c
omm
ent (
5).
For Use With M2-A8–Disk Diffusion M100-S15
37
Tabl
e 2A
Ente
roba
cter
iace
aeM
2-D
isk
Diff
usio
n
©Clinical and Laboratory Standards Institute. All rights reserved.
Tabl
e 2A
. (C
ontin
ued)
Test
/Rep
ort
Gro
up
Ant
imic
robi
al
Age
nt
Dis
k C
onte
nt
Zone
Dia
met
er,
Nea
rest
Who
le m
m
Equi
vale
nt M
ICB
reak
poin
ts (µµ
g/m
L)
Com
men
ts
R
I S
R
S A
MIN
OG
LYC
OSI
DES
(14)
WA
RN
ING
:Fo
r Sa
lmon
ella
spp.
and
Shi
gella
spp.
, am
inog
lyco
side
s m
ay a
ppea
r act
ive
in v
itro
but
are
not e
ffect
ive
clin
ical
ly a
nd s
houl
d no
t be
repo
rted
as s
usce
ptib
le.
AG
enta
mic
in
10 µ
g ≤
1213
-14
≥15
≥8
≤4
BA
mik
acin
30 µ
g≤
1415
-16
≥17
≥32
≤16
C
Kan
amyc
in30
µg
≤13
14-1
7≥
18≥
25≤
6C
N
etilm
icin
30 µ
g≤
1213
-14
≥15
≥32
≤12
C
Tobr
amyc
in10
µg
≤12
13-1
4≥
15≥
8≤
4O
Stre
ptom
ycin
10 µ
g≤
1112
-14
≥15
--
TETR
AC
YCLI
NES
C
Tetra
cycl
ine
30 µ
g≤
1415
-18
≥19
≥16
≤4
(15)
Org
anis
ms
that
are
sus
cept
ible
to
tetra
cycl
ine
are
also
con
side
red
susc
eptib
le t
o do
xycy
clin
e an
dm
inoc
yclin
e.
How
ever
, so
me
orga
nism
s th
at a
rein
term
edia
te
or
resi
stan
t to
te
tracy
clin
e m
ay
besu
scep
tible
to d
oxyc
yclin
e or
min
ocyc
line
or b
oth.
OD
oxyc
yclin
e30
µg
≤12
13-1
5≥
16≥
16≤
4O
Min
ocyc
line
30 µ
g≤
1415
-18
≥19
≥16
≤4
FLU
OR
OQ
UIN
OLO
NES
(1
6) F
luor
oqui
nolo
ne-s
usce
ptib
le s
train
s of
Sal
mon
ella
that
test
res
ista
nt to
nal
idix
ic a
cid
may
be
asso
ciat
edw
ith
clin
ical
fa
ilure
or
de
laye
d re
spon
se
influ
oroq
uino
lone
-trea
ted
patie
nts
with
ex
train
test
inal
salm
onel
losi
s. E
xtra
inte
stin
al i
sola
tes
of S
alm
onel
lash
ould
als
o be
tes
ted
for
resi
stan
ce t
o na
lidix
ic a
cid.
For
isol
ates
tha
t te
st s
usce
ptib
le t
o flu
oroq
uino
lone
san
d re
sist
ant t
o na
lidix
ic a
cid,
the
phys
icia
n sh
ould
be
info
rmed
tha
t th
e is
olat
e m
ay n
ot b
e er
adic
ated
by
fluor
oqui
nolo
ne
treat
men
t. A
cons
ulta
tion
with
an
infe
ctio
us d
isea
se p
ract
ition
er is
reco
mm
ende
d.
B BC
ipro
floxa
cin
or
levo
floxa
cin
5 µg
5 µg
≤
15≤
13
16-2
014
-16
≥21
≥17
≥4
≥8
≤1
≤2
UG
atifl
oxac
in5
µg≤
1415
-17
≥18
≥8
≤2
BG
emifl
oxac
in5
µg≤
1516
-19
≥20
≥1
≤0.
25(1
7) F
DA
-app
rove
d fo
r Kle
bsie
lla p
neum
onia
e.
U U U
Lom
eflo
xaci
n or
norfl
oxac
in o
rof
loxa
cin
10 µ
g10
µg
5 µg
≤18
≤12
≤12
19-2
113
-16
13-1
5
≥22
≥17
≥16
≥8
≥16
≥8
≤2
≤4
≤2
OE
noxa
cin
10 µ
g≤
1415
-17
≥18
≥8
≤2
OG
repa
floxa
cin
5 µg
≤14
15-1
7≥
18≥
4≤
1In
v.Fl
erox
acin
5 µg
≤15
16-1
8≥
19≥
8≤
2
January 2005 Vol. 25 No. 1
38
Tabl
e 2A
Ente
roba
cter
iace
aeM
2-D
isk
Diff
usio
n
©Clinical and Laboratory Standards Institute. All rights reserved.
Tabl
e 2A
. (C
ontin
ued)
Test
/Rep
ort
Gro
upA
ntim
icro
bial
Age
ntD
isk
Con
tent
Zone
Dia
met
er,
Nea
rest
Who
le m
mEq
uiva
lent
MIC
Bre
akpo
ints
(µµg/
mL)
Com
men
tsR
IS
RS
QU
INO
LON
ES
UC
inox
acin
100
µg≤
1415
-18
≥19
≥64
≤16
ON
alid
ixic
aci
d30
µg
≤13
14-1
8≥
19≥
32≤
8S
ee c
omm
ent (
13)
(18)
In a
dditi
on to
test
ing
urin
e is
olat
es, n
alid
ixic
aci
dm
ay b
e us
ed t
o te
st f
or r
educ
ed f
luor
oqui
nolo
nesu
scep
tibili
ty
in
isol
ates
fro
m
patie
nts
with
extra
inte
stin
al S
alm
onel
la i
nfec
tions
. S
ee c
omm
ent
(16)
.FO
LATE
PAT
HW
AYIN
HIB
ITO
RS
BTr
imet
hopr
im-
su
lfam
etho
xazo
le1.
25/
23.7
5 µg
≤10
11-1
5≥
16≥
8/15
2≤
2/38
US
ulfo
nam
ides
250
or30
0 µg
≤12
13-1
6≥
17≥
350
≤
100
(19)
The
sul
fisox
azol
e di
sk c
an b
e us
ed to
repr
esen
tan
y of
th
e cu
rren
tly
avai
labl
e su
lfona
mid
epr
epar
atio
ns.
UTr
imet
hopr
im5
µg≤
1011
-15
≥16
≥16
≤
4
PHEN
ICO
LSC
Chl
oram
phen
icol
30 µ
g≤
1213
-17
≥18
≥32
≤8
(20)
Not
rou
tinel
y re
porte
d on
iso
late
s fro
m t
heur
inar
y tra
ct.
NIT
RO
FUR
AN
TOIN
SU
Nitr
ofur
anto
in30
0 µg
≤14
15-1
6≥
17≥
128
≤32
FOSF
OM
YCIN
SU
Fosf
omyc
in20
0 µg
≤12
13-1
5≥
16≥
256
≤64
(21)
Indi
cate
d fo
r us
e ag
ains
t E. c
olio
nly.
The
200
-µg
fos
fom
ycin
dis
k co
ntai
ns 5
0 µg
of
gluc
ose-
6-ph
osph
ate.
For Use With M2-A8–Disk Diffusion M100-S15
39
Tabl
e 2A
Ente
roba
cter
iace
aeM
2-D
isk
Diff
usio
n
©Clinical and Laboratory Standards Institute. All rights reserved.
Footnotea. Routine screening of Proteus mirabilis for ESBL production is not recommended. However, when it is
deemed clinically relevant (e.g., a bacteremic isolate) the ESBL screen testing zones, ceftazidime (≤≤ 22mm), cefotaxime (≤≤ 27 mm), or cefpodoxime (≤≤ 17 mm) will identify presumptive ESBL production. Thephenotypic confirmatory test using ceftazidime and cefotaxime alone and in combination withclavulanic acid can confirm ESBL-producing strains. For all confirmed ESBL-producing P. mirabilis,the test interpretation should be reported as resistant for all penicillins, cephalosporins, andaztreonam.
b. Preparation of ceftazidime-clavulanic acid (30 µg/10 µg) and cefotaxime-clavulanic acid (30 µg/10 µg) disks:Using a stock solution of clavulanic acid at 1000 µg/mL (either freshly prepared or taken from small aliquots thathave been frozen at -70 °C), add 10 µL of clavulanic acid to ceftazidime (30 µg) and cefotaxime (30 µg) disks.Use a micropipette to apply the 10 µL of stock solution to the ceftazidime and cefotaxime disks within one hourbefore they are applied to the plates, allowing about 30 minutes for the clavulanic acid to absorb and the disksto be dry enough for application. Use disks immediately after preparation or discard; do not store.
Table 2A. (Continued)
Screening and Confirmatory Tests for ESBLs in Klebsiella pneumoniae, K. oxytoca, Escherichia coli, and Proteus mirabilisa
Method Initial Screen Test Phenotypic Confirmatory Test
Medium Mueller-Hinton Agar Mueller-Hinton Agar
Antimicrobial DiskConcentration
Cefpodoxime 10 µg orceftazidime 30 µg oraztreonam 30 µg orcefotaxime 30 µg orceftriaxone 30 µg
(The use of more than one antimicrobialagent for screening improves the sensitivityof detection.)
ceftazidime 30 µgceftazidime-clavulanic acidb 30/10 µgand
cefotaxime 30 µgcefotaxime-clavulanic acidb 30/10 µg
(Confirmatory testing requires use of bothcefotaxime and ceftazidime, alone and incombination with clavulanic acid.)
Inoculum
Standard disk diffusion recommendations Standard disk diffusion recommendationsIncubation conditions
Incubation length
Results Cefpodoxime zone ≤ 17 mmCeftazidime zone ≤ 22 mmAztreonam zone ≤ 27 mmCefotaxime zone ≤ 27 mmCeftriaxone zone ≤ 25 mm= may indicate ESBL production
A ≥ 5-mm increase in a zone diameter for eitherantimicrobial agent tested in combination withclavulanic acid versus its zone when tested alone =ESBL (e.g., ceftazidime zone = 16; ceftazidime-clavulanic acid zone = 21).
QC Recommendations When testing ESBL- screeningantimicrobial agents, K. pneumoniaeATCC® 700603 is provided for qualityassessment (e.g., training, competency,or test evaluation). Either strain, K. pneumoniae ATCC® 700603 or E. coliATCC® 25922, may then be used forroutine QC (e.g., weekly or daily).E. coli ATCC® 25922 (see control limits inTable 3) K. pneumoniae ATCC® 700603:
cefpodoxime zone 9-16 mmceftazidime zone 10-18 mmaztreonam zone 9-17 mmcefotaxime zone 17-25 mmceftriaxone zone 16-24 mm
When performing the ESBL confirmatory tests,K. pneumoniae ATCC® 700603 and E. coliATCC® 25922 should be tested routinely (e.g.,weekly or daily).
E. coli ATCC® 25922: ≤ 2-mm increase in zonediameter for antimicrobial agent tested aloneversus its zone when tested in combination withclavulanic acidK. pneumoniae ATCC® 700603:≥5-mm increase in ceftazidime-clavulanic acidzone diameter; ≥ 3-mm increase in cefotaxime-clavulanic acidzone diameter.
January 2005 Vol. 25 No. 1
40
Tabl
e 2B
Non
-Ent
erob
acte
riace
aeM
2-D
isk
Diff
usio
n
©Clinical and Laboratory Standards Institute. All rights reserved.
Min
imal
QC
Rec
omm
enda
tions
(See
Tab
le 3
for a
ccep
tabl
e Q
C ra
nges
.)
Esch
eric
hia
coli
ATC
C®
2592
2Ps
eudo
mon
as a
erug
inos
aAT
CC
®27
853
Esch
eric
hia
coli
ATC
C®
3521
8 (fo
r β-la
ctam
/β-la
ctam
ase
inhi
bito
rco
mbi
natio
ns)
Test
ing
Con
ditio
ns
Med
ium
: M
uelle
r-H
into
n ag
arIn
ocul
um:
Gro
wth
met
hod
or d
irect
col
ony
susp
ensi
on,
equi
vale
nt t
o a
0.5
McF
arla
nd s
tand
ard
Incu
batio
n: 3
5 ° C
±2
degr
ees;
am
bien
t air;
16
to 1
8 ho
urs;
20
to 2
4 ho
urs
for
Sten
otro
phom
onas
mal
toph
ilia a
nd B
urkh
olde
ria c
epac
ia
Tabl
e 2B
. Zo
ne D
iam
eter
Inte
rpre
tive
Stan
dard
s an
d Eq
uiva
lent
Min
imal
Inhi
bito
ry C
once
ntra
tion
(MIC
) Bre
akpo
ints
for P
seud
omon
as
aeru
gino
sa,A
cine
toba
cter
spp.
, Ste
notr
opho
mon
as m
alto
phili
a, a
ndB
urkh
olde
ria c
epac
ia
Gen
eral
Com
men
ts
(1)
Non
-Ent
erob
acte
riace
ae o
ther
than
P. a
erug
inos
a,Ac
inet
obac
ters
pp.,
S. m
alto
philia
,and
B. c
epac
ia(S
ee c
omm
ent (
5)) s
houl
d be
test
ed b
y th
e di
lutio
n m
etho
d.(S
ee M
7 Ta
ble
2B.)
(2)
The
susc
eptib
ility
of P
. aer
ugin
osa
isol
ated
from
pat
ient
s w
ith c
ystic
fibr
osis
can
be
relia
bly
dete
rmin
ed b
y th
e di
sk m
etho
d, b
ut m
ay re
quire
ext
ende
d in
cuba
tion
up to
24
hour
s be
fore
repo
rting
as
susc
eptib
le.
(3)
P. a
erug
inos
a m
ay d
evel
op r
esis
tanc
e du
ring
prol
onge
d th
erap
y w
ith a
ll an
tibio
tics.
The
refo
re, i
sola
tes
that
are
initi
ally
sus
cept
ible
may
bec
ome
resi
stan
t with
inth
ree
to fo
ur d
ays
afte
r ini
tiatio
n of
ther
apy.
Tes
ting
of re
peat
isol
ates
may
be
war
rant
ed.
(4)
Rx:
P. a
erug
inos
ain
fect
ions
in
gran
uloc
ytop
enic
pat
ient
s an
d se
rious
inf
ectio
ns i
n ot
her
patie
nts
shou
ld b
e tre
ated
with
max
imum
dos
es o
f th
e se
lect
edan
tipse
udom
onal
pen
icill
in (c
arbo
xype
nici
llin
or u
reid
open
icill
in) o
r cef
tazi
dim
e in
com
bina
tion
with
an
amin
ogly
cosi
de.
(5)
Onl
y m
inoc
yclin
e, le
voflo
xaci
n, a
nd tr
imet
hopr
im-s
ulfa
met
hoxa
zole
may
be
repo
rted
for
S. m
alto
philia
isol
ates
. Onl
y ce
ftazi
dim
e, m
erop
enem
, min
ocyc
line,
and
trim
etho
prim
-sul
fam
etho
xazo
le m
ay b
e re
porte
d fo
rB. c
epac
iais
olat
es.
NO
TE:
Info
rmat
ion
in b
oldf
ace
type
is c
onsi
dere
d te
ntat
ive
for o
ne y
ear.
Test
/Rep
ort
Gro
up
Ant
imic
robi
al
Age
nt
Dis
k C
onte
nt
Zone
Dia
met
er,
Nea
rest
Who
le m
m
Equi
vale
nt M
ICB
reak
poin
ts (µµ
g/m
L)
Com
men
tsR
I
S R
S
PEN
ICIL
LIN
SA A A
Mez
loci
llin
or
ticar
cilli
n
Pip
erac
illin
75 µ
g
75 µ
g
100
µg
≤15
≤17
≤14
≤14
≤17
≤17
-18
-20
-15
-19
-18
-20
≥16
≥21
≥15
≥20
≥18
≥21
≥12
8≥
128
≥12
8≥
128
≥12
8≥
128
≤64
≤16
≤64
≤16
≤64
≤16
For P
. aer
ugin
osa
For A
cine
toba
cter
spp.
For P
. aer
ugin
osa
For A
cine
toba
cter
spp.
For P
. aer
ugin
osa
For A
cine
toba
cter
spp.
UC
arbe
nici
llin
100
µg≤
13≤
1914
-16
20-2
2≥
17≥
23≥
512
≥64
≤12
8≤
16Fo
r P. a
erug
inos
aFo
r Aci
neto
bact
ersp
p.O
Azl
ocill
in75
µg
≤17
- ≥
18≥
128
≤64
For P
. aer
ugin
osa
For Use With M2-A8–Disk Diffusion M100-S15
41
Tabl
e 2B
Non
-Ent
erob
acte
riace
aeM
2-D
isk
Diff
usio
n
©Clinical and Laboratory Standards Institute. All rights reserved.
Tabl
e 2B
. (C
ontin
ued)
Test
/Rep
ort
Gro
up
Ant
imic
robi
al
Age
nt
Dis
k C
onte
nt
Zone
Dia
met
er,
Nea
rest
Who
le m
m
Equi
vale
nt M
ICB
reak
poin
ts (µµ
g/m
L)
Com
men
tsR
I
S R
S
ββ -LA
CTA
M/ββ
-LA
CTA
MA
SE IN
HIB
ITO
R C
OM
BIN
ATIO
NS
OA
mpi
cilli
n-su
lbac
tam
10/1
0 µg
≤11
12-1
4≥
15≥
32/1
6≤
8/4
(6) M
ay b
e re
porte
d fo
r Aci
neto
bact
ersp
p. re
sist
ant
to o
ther
age
nts.
OP
iper
acill
in-ta
zoba
ctam
100/
10 µ
g10
0/10
µg
≤17
≤17
-18
-20
≥18
≥21
≥12
8/4
≥12
8/4
≤64
/4≤
16/4
For P
. aer
ugin
osa
For A
cine
toba
cter
spp.
OTi
carc
illin
-cla
vula
nic
acid
75/1
0 µg
75/1
0 µg
≤14
≤14
-15
-19
≥15
≥20
≥12
8/2
≥12
8/2
≤64
/2≤
16/2
For P
. aer
ugin
osa
For A
cine
toba
cter
spp.
CEP
HEM
S (P
AR
ENTE
RA
L) (
Incl
udin
g ce
phal
ospo
rins
I, II,
III,
and
IV. P
leas
e re
fer
to G
loss
ary
I.)A
Cef
tazi
dim
e30
µg
≤14
≤17
15-1
718
-20
≥18
≥21
≥32 -
≤8
-Fo
r B. c
epac
iaB
Cef
epim
e30
µg
≤14
15-1
7≥
18≥
32≤
8B
C
efop
eraz
one
75 µ
g≤
15
16-2
0≥
21≥
64≤
16C C
Cef
otax
ime
orce
ftria
xone
30
µg
30 µ
g≤
14≤
1315
-22
14-2
0≥
23≥
21≥
64≥
64≤
8≤
8U
Cef
tizox
ime
30 µ
g≤
1415
-19
≥20
≥32
≤8
OM
oxal
acta
m
30 µ
g≤
1415
-22
≥23
≥64
≤8
CA
RB
APE
NEM
SB
Imip
enem
10 µ
g≤
1314
-15
≥16
≥16
≤4
BM
erop
enem
10 µ
g≤
13≤
15
14-1
516
-19
≥16
≥20
≥16 -
≤4
-Fo
r B. c
epac
iaM
ON
OB
AC
TAM
SB
Azt
reon
am30
µg
≤15
16-2
1≥
22≥
32≤
8A
MIN
OG
LYC
OSI
DES
AG
enta
mic
in10
µg
≤12
13-1
4≥
15≥
8≤
4B
Am
ikac
in30
µg
≤14
15-1
6≥
17≥
32≤
16B
Tobr
amyc
in10
µg
≤12
13-1
4≥
15≥
8≤
4C
Net
ilmic
in30
µg
≤12
13-1
4≥
15≥
32≤
12TE
TRA
CYC
LIN
ESU
Tetra
cycl
ine
30 µ
g≤
1415
-18
≥19
≥16
≤4
(7)
Org
anis
ms
that
are
sus
cept
ible
to
tetra
cycl
ine
are
also
con
side
red
susc
eptib
le to
dox
ycyc
line
and
min
ocyc
line.
H
owev
er,
som
e or
gani
sms
that
are
inte
rmed
iate
or
resi
stan
t to
tet
racy
clin
e m
ay b
esu
scep
tible
to d
oxyc
yclin
e or
min
ocyc
line
or b
oth.
OD
oxyc
yclin
e30
µg
≤12
13-1
5≥
16≥
16≤
4 O
Min
ocyc
line
30 µ
g≤
1415
-18
≥19
≥16
≤4
42
Tabl
e 2B
Non
-Ent
erob
acte
riace
aeM
2-D
isk
Diff
usio
n
©Clinical and Laboratory Standards Institute. All rights reserved.
January 2005 Vol. 25 No. 1
Tabl
e 2B
. (C
ontin
ued)
Test
/Rep
ort
Gro
up
Ant
imic
robi
al
Age
nt
Dis
k C
onte
nt
Zone
Dia
met
er,
Nea
rest
Who
le m
m
Equi
vale
nt M
ICB
reak
poin
ts (µµ
g/m
L)
Com
men
ts
R
I S
R
S FL
UO
RO
QU
INO
LON
ESB B
Cip
roflo
xaci
nLe
voflo
xaci
n5
µg5
µg≤
15≤
1316
-20
14-1
6≥
21≥
17≥
4≥
8≤
1≤
2U U U
Lom
eflo
xaci
n or
norfl
oxac
in o
rof
loxa
cin
10 µ
g10
µg
5 µg
≤18
≤12
≤12
19-2
113
-16
13-1
5
≥22
≥17
≥16
≥8
≥16
≥8
≤2
≤4
≤2
O
Gat
iflox
acin
5 µg
≤
1415
-17
≥18
≥8
≤2
(8)
This
bre
akpo
int
appl
ies
to i
sola
tes
from
the
urin
ary
tract
onl
y.
PHEN
ICO
LS
CC
hlor
amph
enic
ol30
µg
≤12
13-1
7≥
18≥
32≤
8(9
) N
ot
rout
inel
y re
porte
d on
is
olat
es
from
th
eur
inar
y tra
ct.
FOLA
TE P
ATH
WAY
INH
IBIT
OR
SC
Trim
etho
prim
-sul
fam
etho
xazo
le1.
25/2
3.75
µg
≤10
11-1
5≥
16≥
8/15
2≤
2/38
US
ulfo
nam
ides
250
µg o
r30
0 µg
≤12
13-1
6≥
17≥
350
≤10
0(1
0)
The
sulfi
soxa
zole
di
sk
can
be
used
to
repr
esen
t an
y of
th
e cu
rren
tly
avai
labl
esu
lfona
mid
e pr
epar
atio
ns.
For Use With M2-A8–Disk Diffusion M100-S15
43©Clinical and Laboratory Standards Institute. All rights reserved.
This page is intentionally left blank.
January 2005 Vol. 25 No. 1
44
Tabl
e 2C
Stap
hylo
cocc
ussp
p.M
2-D
isk
Diff
usio
n
©Clinical and Laboratory Standards Institute. All rights reserved.
Tabl
e 2C
. Zo
ne D
iam
eter
Inte
rpre
tive
Stan
dard
s an
d Eq
uiva
lent
Min
imal
Inhi
bito
ry C
once
ntra
tion
(MIC
) Bre
akpo
ints
for S
taph
yloc
occu
ssp
p.
Test
ing
Con
ditio
ns
Med
ium
:M
uelle
r-H
into
n ag
arIn
ocul
um:
Dire
ct c
olon
y su
spen
sion
, equ
ival
ent t
o a
0.5
McF
arla
nd s
tand
ard
Incu
batio
n:33
to35
°C
(do
not e
xcee
d 35
°C
); am
bien
t air;
16
to 1
8 ho
urs;
24
hour
s fo
r oxa
cilli
n, m
ethi
cilli
n,na
fcill
in, a
nd v
anco
myc
in
Min
imal
QC
Rec
omm
enda
tions
(See
Tab
le 3
for a
ccep
tabl
e Q
C ra
nges
.)
Stap
hylo
cocc
us a
ureu
sAT
CC
®25
923
Esch
eric
hia
coli
ATC
C®
352
18 (f
or β
-lact
am/β
-lact
amas
e in
hibi
tor
com
bina
tions
)
Stap
hylo
cocc
us a
ureu
sAT
CC
® B
AA
-977
and
Sta
phyl
ococ
cus
aure
usAT
CC
® B
AA
-976
(for
qua
lity
asse
ssm
ent o
f the
clin
dam
ycin
indu
ctio
n te
st)
Gen
eral
Com
men
ts(1
)H
isto
rical
ly, r
esis
tanc
e to
the
pen
icill
inas
e-st
able
pen
icill
ins
(see
Glo
ssar
y I)
has
bee
n re
ferr
ed t
o as
“m
ethi
cilli
n re
sist
ance
,” th
us t
he a
cron
yms
MR
SA
(for
“met
hici
llin-
resi
stan
tS. a
ureu
s”) o
r MR
S (f
or “m
ethi
cilli
n-re
sist
ant s
taph
yloc
occi
”) a
re s
till c
omm
only
use
d ev
en th
ough
met
hici
llin
is n
o lo
nger
the
agen
t of c
hoic
efo
r te
stin
g or
trea
tmen
t. In
this
doc
umen
t, re
sist
ance
to th
ese
agen
ts m
ay b
e re
ferr
ed to
usi
ng s
ever
al te
rms
(e.g
., “M
RS
,” “m
ethi
cilli
n re
sist
ance
,” or
“ox
acill
inre
sist
ance
”).
(2)
For o
xaci
llin-
susc
eptib
le S
taph
yloc
occu
s au
reus
and
coag
ulas
e-ne
gativ
e st
aphy
loco
cci,
resu
lts fo
r par
ente
ral a
nd o
ral c
ephe
ms,
ββ-la
ctam
/ββ-la
ctam
ase
inhi
bito
r co
mbi
natio
ns, a
nd c
arba
pene
ms,
if t
este
d, s
houl
d be
rep
orte
d ac
cord
ing
to t
he r
esul
ts g
ener
ated
usi
ng r
outin
e in
terp
retiv
e cr
iteria
. See
com
men
t (3)
for
repo
rtin
g ββ -
lact
am r
esul
ts o
n ox
acill
in-r
esis
tant
str
ains
.
(3)
WA
RN
ING
:Fo
r ox
acill
in-r
esis
tant
Sta
phyl
ococ
cus
aure
usan
d co
agul
ase-
nega
tive
stap
hylo
cocc
i (M
RS
), ot
her
ββ -la
ctam
age
nts,
i.e.
, pen
icill
ins,
ββ-la
ctam
/ββ-
lact
amas
e in
hibi
tor
com
bina
tions
,cep
hem
s, a
nd c
arba
pene
ms,
may
app
ear a
ctiv
e in
vitr
obu
t are
not
effe
ctiv
e cl
inic
ally.
Res
ults
for t
hese
dru
gs s
houl
d be
repo
rted
as r
esis
tant
or
shou
ld n
ot b
e re
porte
d. T
his
is b
ecau
se m
ost
case
s of
doc
umen
ted
MR
S in
fect
ions
hav
e re
spon
ded
poor
ly t
o β-
lact
am t
hera
py,
orbe
caus
e co
nvin
cing
clin
ical
dat
a ha
ve y
et to
be
pres
ente
d th
at d
ocum
ent c
linic
al e
ffica
cy fo
r tho
se a
gent
s.
(4)
Det
ectio
n of
oxa
cilli
n re
sist
ance
: Tes
ts fo
r m
ecA
or fo
r th
e pr
otei
n ex
pres
sed
by m
ecA
, the
pen
icill
in-b
indi
ng p
rote
in 2
a (P
BP
2a, a
lso
calle
d PB
P2')
are
the
mos
t acc
urat
e m
etho
ds fo
r pre
dict
ion
of re
sist
ance
to o
xaci
llin
and
can
be u
sed
to c
onfir
m d
isk
test
resu
lts fo
r iso
late
s of
sta
phyl
ococ
ci fr
omse
rious
infe
ctio
ns. I
sola
tes
of s
taph
yloc
occi
tha
t ca
rry
the
mec
Age
ne, o
r th
at p
rodu
ce P
BP
2a (
the
mec
Age
ne p
rodu
ct),
shou
ld b
e re
port
ed a
sox
acill
in r
esis
tant
. Is
olat
es t
hat
do n
ot c
arry
mec
Aor
do
not
prod
uce
PBP
2a s
houl
d be
rep
orte
d as
oxa
cilli
n su
scep
tible
. B
ecau
se o
f th
e ra
reoc
curr
ence
of r
esis
tanc
e m
echa
nism
s ot
her t
han
mec
A, i
f MIC
test
s ar
e pe
rfor
med
in a
dditi
on to
dis
k di
ffusi
on, i
sola
tes
for w
hich
oxa
cilli
n M
ICs
are
≥≥4
µg/m
Lan
d ar
e m
ecA
nega
tive
or P
BP
2a n
egat
ive
shou
ld b
e re
port
ed a
s ox
acill
in r
esis
tant
.
(5)
Rou
tine
test
ing
of u
rine
isol
ates
of
S. s
apro
phyt
icus
is n
ot a
dvis
ed,
beca
use
infe
ctio
ns r
espo
nd t
o co
ncen
tratio
ns a
chie
ved
in u
rine
of a
ntim
icro
bial
age
nts
com
mon
ly u
sed
to tr
eat a
cute
, unc
ompl
icat
ed u
rinar
y tra
ct in
fect
ions
(e.g
., ni
trofu
rant
oin,
trim
etho
prim
± s
ulfa
met
hoxa
zole
, or a
fluo
roqu
inol
one)
.
(6)
For
som
e or
gani
sm/a
ntim
icro
bial
age
nt c
ombi
natio
ns, t
he a
bsen
ce o
f res
ista
nt s
train
s pr
eclu
des
defin
ing
any
resu
lts c
ateg
orie
s ot
her
than
“su
scep
tible
.” Fo
rst
rain
s yi
eldi
ng r
esul
ts s
ugge
stiv
e of
a “
nons
usce
ptib
le”
cate
gory
, or
gani
sm i
dent
ifica
tion
and
antim
icro
bial
sus
cept
ibili
ty t
est
resu
lts s
houl
d be
con
firm
ed.
Sub
sequ
ently
, the
isol
ates
sho
uld
be s
aved
and
sub
mitt
ed to
a re
fere
nce
labo
rato
ry th
at w
ill c
onfir
m re
sults
usi
ng a
CLS
I/NC
CLS
refe
renc
e di
lutio
n m
etho
d.
NO
TE:
Info
rmat
ion
in b
oldf
ace
type
is c
onsi
dere
d te
ntat
ive
for o
ne y
ear.
For Use With M2-A8–Disk Diffusion M100-S15
45
Tabl
e 2C
Stap
hylo
cocc
ussp
p.M
2-D
isk
Diff
usio
n
©Clinical and Laboratory Standards Institute. All rights reserved.
Tabl
e 2C
. (C
ontin
ued)
Test
/Rep
ort
Gro
up
Ant
imic
robi
al
Age
nt
Dis
k C
onte
nt
Zone
Dia
met
er,
Nea
rest
Who
le m
m
Equi
vale
nt M
ICB
reak
poin
ts (µµ
g/m
L)
Com
men
tsR
I
S R
S
PEN
ICIL
LIN
S(7
) P
enic
illin
-sus
cept
ible
st
aphy
loco
cci
are
also
susc
eptib
le
to
othe
r pe
nici
llins
, β-
lact
am/β
-lact
amas
ein
hibi
tor
com
bina
tions
, ce
phem
s,
and
carb
apen
ems
appr
oved
fo
r us
e by
th
e FD
Afo
r st
aphy
loco
ccal
infe
ctio
ns.
Pen
icill
in-r
esis
tant
, ox
acill
in-s
usce
ptib
lest
rain
s ar
e re
sist
ant
to p
enic
illin
ase-
labi
le p
enic
illin
s bu
tsu
scep
tible
to
othe
r pe
nici
llina
se-s
tabl
e pe
nici
llins
, β-
lact
am/β
-lact
amas
e in
hibi
tor
com
bina
tions
, re
leva
ntce
phem
s,
and
carb
apen
ems.
O
xaci
llin-
resi
stan
tst
aphy
loco
cci
are
resi
stan
t to
all
curr
ently
ava
ilabl
e β-
lact
am a
ntib
iotic
s. T
hus,
sus
cept
ibili
ty o
r re
sist
ance
to a
wid
e ar
ray
of β
-lact
am a
ntib
iotic
s m
ay b
e de
duce
d fro
mte
stin
g on
ly p
enic
illin
and
oxa
cilli
n. R
outin
e te
stin
g of
othe
r pe
nici
llins
, β-
lact
am/β
-lact
amas
e in
hibi
tor
com
bina
tions
, ce
phem
s,
and
carb
apen
ems
is
not
advi
sed.
See
com
men
t (3)
. A
Pen
icill
in10
uni
ts≤
28-
≥29
β-la
ctam
ase
≤0.
12(8
) P
enic
illin
-res
ista
nt,
oxac
illin
-sus
cept
ible
stra
ins
ofSt
aphy
loco
ccus
aur
eus
prod
uce
β-la
ctam
ase,
and
the
test
ing
of
the
10-u
nit
peni
cilli
n di
sk
inst
ead
of
the
ampi
cilli
n di
sk is
pre
ferr
ed.
Pen
icill
in s
houl
d be
use
d to
test
the
susc
eptib
ility
of a
ll β-
lact
amas
e-la
bile
pen
icill
ins,
such
as
am
pici
llin,
am
oxic
illin
, az
loci
llin,
ca
rben
icill
in,
mez
loci
llin,
pip
erac
illin
, and
tica
rcill
in. L
ikew
ise,
a p
ositi
veβ-
lact
amas
e te
st
(see
M
2-A
8,
Sec
tion
8)
pred
icts
resi
stan
ce
to
thes
e ag
ents
. Fo
r ox
acill
in-r
esis
tant
stap
hylo
cocc
i, re
port
as re
sist
ant o
r do
not r
epor
t.
January 2005 Vol. 25 No. 1
46
Tabl
e 2C
Stap
hylo
cocc
ussp
p.M
2-D
isk
Diff
usio
n
©Clinical and Laboratory Standards Institute. All rights reserved.
Tabl
e 2C
. (C
ontin
ued)
Test
/Rep
ort
Gro
up
Ant
imic
robi
al
Age
nt
Dis
k C
onte
nt
Zone
Dia
met
er,
Nea
rest
Who
le m
m
Equi
vale
nt M
IC B
reak
poin
ts(µµ
g/m
L)
Com
men
ts
R
I S
R
S PE
NIC
ILLI
NS
(Con
tinue
d)A
Oxa
cilli
n30
µµg
cefo
xitin
1 µg
oxa
cilli
n
30 µµ
g ce
foxi
tin
1 µg
oxa
cilli
n
≤≤19
≤10
≤≤24
≤17
-
11-1
2 - -
≥≥20
≥13
≥≥25
≥18
≥≥4
(oxa
cilli
n)
≥4
≥0.
5 (o
xaci
llin)
≥0.
5
≤2
≤2
≤0.
25
≤0.
25
For
S. a
ureu
san
d S.
lugd
unen
sis
For S
. aur
eus
and
S. lu
gdun
ensi
s
(9)
For
S. a
ureu
san
d S.
lugd
unen
sis,
the
cefo
xitin
dis
k te
stis
com
para
ble
to th
e ox
acill
in d
isk
test
for p
redi
ctio
n of
mec
A-
med
iate
d re
sist
ance
to
oxac
illin
; ho
wev
er, t
he c
efox
itin
disk
test
is e
asie
r to
rea
d an
d th
us is
the
pref
erre
d m
etho
d.
(10)
If in
term
edia
te re
sults
are
obt
aine
d fo
r S. a
ureu
s,pe
rfor
mte
stin
g fo
r mec
Aor
PB
P2a
, the
cef
oxiti
n di
sk te
st, a
n ox
acill
inM
IC te
st, o
r th
e ox
acill
in-s
alt a
gar
scre
enin
g te
st. R
epor
t the
resu
lt of
the
alte
rnat
ive
test
rat
her
than
the
int
erm
edia
tere
sult.
For
coag
ulas
e-ne
gativ
e st
aphy
loco
cci e
xcep
tS. l
ugdu
nens
is
For c
oagu
lase
-neg
ativ
e st
aphy
loco
cci e
xcep
tS. l
ugdu
nens
is
(11)
The
cef
oxiti
n di
sk te
st is
the
pref
erre
d m
etho
d fo
r tes
ting
coag
ulas
e-ne
gativ
e st
aphy
loco
cci.
Alth
ough
ox
acill
inin
terp
retiv
e cr
iteria
fo
r co
agul
ase-
nega
tive
stap
hylo
cocc
ico
rrel
ate
with
the
pres
ence
or
abse
nce
of th
e ge
ne e
ncod
ing
met
hici
llin/
oxac
illin
re
sist
ance
(m
ecA
) in
S.
epi
derm
idis
,th
ese
inte
rpre
tive
crite
ria m
ay o
verc
all
resi
stan
ce f
or o
ther
coag
ulas
e-ne
gativ
e st
aphy
loco
cci,
e.g.
, S.
sap
roph
ytic
us.
The
cefo
xitin
dis
k te
st h
as h
ighe
r sp
ecifi
city
and
equ
alse
nsiti
vity
to
the
oxac
illin
dis
k te
st f
or c
oagu
lase
-neg
ativ
est
aphy
loco
cci.
(12)
If
a pe
nici
llina
se-s
tabl
e pe
nici
llin
is t
este
d, o
xaci
llin
isth
e pr
efer
red
agen
t an
d re
sults
can
be
appl
ied
to t
he o
ther
peni
cilli
nase
-sta
ble
peni
cilli
ns,
clox
acill
in,
dicl
oxac
illin
, an
dflu
clox
acill
in.
Oxa
cilli
n is
mor
e re
sist
ant
to d
egra
datio
n in
stor
age
and
is
mor
e lik
ely
to
dete
ct
hete
rore
sist
ant
stap
hylo
cocc
al s
trai
ns. C
loxa
cilli
n di
sks
shou
ld n
ot b
e us
ed,
beca
use
they
may
not
det
ect
oxac
illin
-res
ista
nt S
. au
reus
.C
efox
itin
may
be
test
ed in
stea
d of
oxa
cilli
n. S
ee c
omm
ents
(9),
(10)
, (11
), an
d (1
3).
(13)
Fo
r al
l st
aphy
loco
cci,
read
the
oxa
cilli
n di
sk f
or l
ight
grow
th w
ithin
the
zon
e of
inh
ibiti
on u
sing
tra
nsm
itted
lig
ht(p
late
hel
d up
to
light
); an
y di
scer
nabl
e gr
owth
with
in t
hezo
ne o
f in
hibi
tion
is in
dica
tive
of o
xaci
llin
resi
stan
ce.
Rea
dth
e ce
foxi
tin d
isk
usin
g re
flect
ed li
ght.
For Use With M2-A8–Disk Diffusion M100-S15
47
Tabl
e 2C
Stap
hylo
cocc
ussp
p.M
2-D
isk
Diff
usio
n
©Clinical and Laboratory Standards Institute. All rights reserved.
Tabl
e 2C
. (C
ontin
ued)
Test
/Rep
ort
Gro
up
Ant
imic
robi
al
Age
nt
Dis
k C
onte
nt
Zone
Dia
met
er,
Nea
rest
Who
le m
m
Equi
vale
nt M
ICB
reak
poin
ts (µµ
g/m
L)
Com
men
tsR
I
S R
S
PEN
ICIL
LIN
S (C
ontin
ued)
OA
mpi
cilli
n10
µg
≤28
- ≥
29β-
lact
amas
e≤
0.25
(14)
Cla
ss re
pres
enta
tive
for a
mpi
cilli
n an
d am
oxic
illin
. (1
5) F
or o
xaci
llin-
resi
stan
t sta
phyl
ococ
ci, r
epor
t as
resi
stan
t or
do n
ot re
port.
OM
ethi
cilli
n5
µg
≤9
10-1
3≥
14≥
16≤
8(1
6) D
isk
diffu
sion
bre
akpo
ints
are
for u
se w
ith S
. aur
eus
only.
See
com
men
t (12
).O
Naf
cilli
n 1
µg≤
1011
-12
≥13
- ≤
1(1
7) D
isk
diffu
sion
bre
akpo
ints
are
for u
se w
ith S
. aur
eus
only.
See
com
men
t (12
).ββ -
LAC
TAM
/ββ-L
AC
TAM
ASE
INH
IBIT
OR
CO
MB
INAT
ION
SS
ee c
omm
ents
(3) a
nd (7
).(1
8) F
or o
xaci
llin-
resi
stan
t sta
phyl
ococ
ci, r
epor
t as
resi
stan
t or
do n
ot re
port.
OA
mox
icill
in-c
lavu
lani
c ac
id
20/1
0 µg
≤19
- ≥
20≥
8/4
≤4/
2O
Am
pici
llin-
sulb
acta
m10
/10
µg≤
1112
-14
≥15
≥32
/16
≤8/
4O
Pip
erac
illin
-tazo
bact
am10
0/10
µg
≤17
- ≥
18≥
16/4
≤8/
4O
Tica
rcill
in-c
lavu
lani
c ac
id75
/10
µg≤
22-
≥23
≥16
/2≤
8/2
CEP
HEM
S (P
AR
ENTE
RA
L) (
Incl
udin
g ce
phal
ospo
rins
I, II,
III,
and
IV. P
leas
e re
fer
to G
loss
ary
I.)S
ee c
omm
ent (
7).
(19)
For
oxa
cilli
n-re
sist
ant s
taph
yloc
occi
, rep
ort a
s re
sist
ant o
rdo
not
repo
rt.O
Cef
aman
dole
30 µ
g≤
1415
-17
≥18
≥32
≤8
OC
efaz
olin
30
µg
≤14
15-1
7≥
18≥
32≤
8O
Cef
epim
e 30
µg
≤14
15-1
7≥
18≥
32≤
8O
Cef
met
azol
e30
µg
≤12
13-1
5≥
16≥
64≤
16O
Cef
onic
id30
µg
≤14
15-1
7≥
18≥
32≤
8O
Cef
oper
azon
e75
µg
≤15
16-2
0≥
21≥
64≤
16O
Cef
otax
ime
30 µ
g ≤
1415
-22
≥23
≥64
≤8
OC
efot
etan
30 µ
g≤
1213
-15
≥16
≥64
≤16
OC
efta
zidi
me
30 µ
g≤
1415
-17
≥18
≥32
≤8
OC
eftiz
oxim
e30
µg
≤14
15-1
9≥
20≥
32≤
8O
Cef
triax
one
30 µ
g≤
1314
-20
≥21
≥64
≤8
OC
efur
oxim
e so
dium
(par
ente
ral)
30 µ
g≤
1415
-17
≥18
≥32
≤
8O
Cep
halo
thin
30 µ
g≤
1415
-17
≥18
≥32
≤8
OM
oxal
acta
m
30 µ
g≤
1415
-22
≥23
≥64
≤
8C
EPH
EMS
(OR
AL)
S
ee c
omm
ent (
7).
(20)
For
oxa
cilli
n-re
sist
ant s
taph
yloc
occi
, rep
ort a
s re
sist
ant o
r do
not
repo
rt.O
Cef
aclo
r 30
µg
≤14
15
-17
≥18
≥
32≤
8O
Cef
dini
r 5
µg≤
1617
-19
≥20
≥4
≤1
OC
efpo
doxi
me
10 µ
g≤
17
18-2
0 ≥
21
≥8
≤2
O
Cef
proz
il 30
µg
≤14
15-1
7 ≥
18≥
32≤
8O
Cef
urox
ime
axet
il (o
ral)
30 µ
g≤
1415
-22
≥23
≥32
≤
4O
Lora
carb
ef
30 µ
g≤
1415
-17
≥18
≥32
≤8
January 2005 Vol. 25 No. 1
48
Tabl
e 2C
Stap
hylo
cocc
ussp
p.M
2-D
isk
Diff
usio
n
Tabl
e 2C
. (C
ontin
ued)
Test
/Rep
ort
Gro
up
Ant
imic
robi
al
Age
nt
Dis
k C
onte
nt
Zone
Dia
met
er,
Nea
rest
Who
le m
m
Equi
vale
nt M
ICB
reak
poin
ts (µµ
g/m
L)
Com
men
tsR
I
S R
S
CA
RB
APE
NEM
SS
ee c
omm
ent (
7)(2
1) F
or o
xaci
llin-
resi
stan
t sta
phyl
ococ
ci, r
epor
t as
resi
stan
t or
do n
ot re
port.
O
Erta
pene
m
10 µ
g ≤
1516
-18
≥19
≥8
≤2
OIm
ipen
em
10 µ
g≤
1314
-15
≥16
≥16
≤4
OM
erop
enem
10
µg
≤13
14-1
5 ≥
16≥
16≤
4G
LYC
OPE
PTID
ESB
Va
ncom
ycin
30 µ
g-
- ≥
15-
≤4
(22)
A
ll st
aphy
loco
ccal
iso
late
s fo
r w
hich
van
com
ycin
zon
edi
amet
ers
are
14 m
m o
r les
s sh
ould
be
test
ed b
y a
refe
renc
e M
ICm
etho
d.
The
disk
di
ffusi
on
proc
edur
e w
ill
not
diffe
rent
iate
stra
ins
with
red
uced
sus
cept
ibili
ty t
o va
ncom
ycin
(M
ICs
4-8
µµ g/m
L) f
rom
sus
cept
ible
str
ains
(M
IC r
ange
0.5
-2 µµ
g/m
L) e
ven
whe
n in
cuba
ted
for 2
4 ho
urs.
Add
ition
ally
, van
com
ycin
-res
ista
ntS.
aur
eus
(VR
SA)
stra
ins
(MIC
s ≥≥ 3
2 µµ g
/mL)
may
pro
duce
onl
ysu
btle
gro
wth
aro
und
a va
ncom
ycin
dis
k. A
BH
I van
com
ycin
aga
rsc
reen
pla
te c
onta
inin
g 6
µµ g/m
Lof
van
com
ycin
, su
ch a
s th
atus
ed fo
r det
ectio
n of
van
com
ycin
-res
ista
nt e
nter
ococ
ci (s
ee M
7,Ta
ble
2D),
may
be
inoc
ulat
ed t
o en
hanc
e th
e se
nsiti
vity
of
dete
ctin
g va
ncom
ycin
-inte
rmed
iate
an
d va
ncom
ycin
-res
ista
ntst
rain
s of
S. a
ureu
s. S
end
any
stap
hylo
cocc
i det
erm
ined
to h
ave
anel
evat
ed M
IC to
van
com
ycin
(≥4
µg/m
L) to
a re
fere
nce
labo
rato
ry.
Inv.
Teic
opla
nin
30 µ
g≤
1011
-13
≥14
≥32
≤
8LI
POPE
PTID
ESB
Dap
tom
ycin
30 µµ
g-
-≥≥
16-
≤≤1
See
com
men
t (6)
.
AM
INO
GLY
CO
SID
ESC
Gen
tam
icin
10 µ
g≤
1213
-14
≥15
≥8
≤4
OA
mik
acin
30 µ
g≤
1415
-16
≥17
≥32
≤16
OK
anam
ycin
30 µ
g≤
1314
-17
≥18
≥25
≤6
ON
etilm
icin
30 µ
g≤
1213
-14
≥15
≥32
≤12
OTo
bram
ycin
10 µ
g≤
1213
-14
≥15
≥8
≤4
MA
CR
OLI
DES
B B B
Azi
thro
myc
in o
rcl
arith
rom
ycin
or
eryt
hrom
ycin
15 µ
g15
µg
15 µ
g
≤13
≤13
≤13
14-1
714
-17
14-2
2
≥18
≥18
≥23
≥8
≥8
≥8
≤2
≤2
≤0.
5
(23)
Not
rout
inel
y re
porte
d on
isol
ates
from
the
urin
ary
tract
.
O
Diri
thro
myc
in15
µg
≤15
16-1
8≥
19≥
8≤
2K
ETO
LID
ESB
Telit
hrom
ycin
15 µ
g≤
1819
-21
≥22
≥4
≤1
©Clinical and Laboratory Standards Institute. All rights reserved.
For Use With M2-A8–Disk Diffusion M100-S15
49
Tabl
e 2C
Stap
hylo
cocc
ussp
p.M
2-D
isk
Diff
usio
n
©Clinical and Laboratory Standards Institute. All rights reserved.
Tabl
e 2C
. (C
ontin
ued)
Test
/Rep
ort
Gro
up
Ant
imic
robi
al
Age
nt
Dis
k C
onte
nt
Zone
Dia
met
er,
Nea
rest
Who
le m
m
Equi
vale
nt M
ICB
reak
poin
ts (µµ
g/m
L)
Com
men
ts
R
I S
R
S TE
TRA
CYC
LIN
ES
C
Tetra
cycl
ine
30 µ
g≤
1415
-18
≥19
≥16
≤4
(24)
Org
anis
ms
that
are
sus
cept
ible
to
tetra
cycl
ine
are
also
cons
ider
ed s
usce
ptib
le to
dox
ycyc
line
and
min
ocyc
line.
How
ever
,so
me
orga
nism
s th
at a
re in
term
edia
te o
r re
sist
ant t
o te
tracy
clin
em
ay b
e su
scep
tible
to d
oxyc
yclin
e or
min
ocyc
line
or b
oth.
O
Dox
ycyc
line
30 µ
g ≤
1213
-15
≥16
≥16
≤4
O
Min
ocyc
line
30 µ
g≤
1415
-18
≥19
≥16
≤4
FLU
OR
OQ
UIN
OLO
NES
(25)
St
aphy
loco
ccus
spp.
m
ay
deve
lop
resi
stan
ce
durin
gpr
olon
ged
ther
apy
with
qui
nolo
nes.
The
refo
re,
isol
ates
tha
t ar
ein
itial
ly s
usce
ptib
le m
ay b
ecom
e re
sist
ant w
ithin
thre
e to
four
day
saf
ter
initi
atio
n of
the
rapy
. Te
stin
g of
rep
eat
isol
ates
may
be
war
rant
ed.
C C C C C
Cip
roflo
xaci
n or
le
voflo
xaci
n or
oflo
xaci
nG
atifl
oxac
in o
rm
oxifl
oxac
in
5 µg
5 µg
5 µg
5 µg
5
µµ g
≤15
≤≤15
≤≤14
≤≤19
≤≤20
16-2
016
-18
15-1
720
-22
21-2
3
≥21
≥≥19
≥≥18
≥≥23
≥≥24
≥4
≥4
≥4
≥≥2
≥≥2
≤1
≤1
≤1
≤≤0.
5 ≤≤
0.5
U U
Lom
eflo
xaci
n or
norfl
oxac
in
10 µ
g10
µg
≤18
≤12
19-2
113
-16
≥22
≥17
≥8
≥16
≤
2≤
4
O
Eno
xaci
n 10
µg
≤14
15-1
7≥
18
≥8
≤2
(26)
FD
A-a
ppro
ved
for S
. sap
roph
ytic
usan
d S.
epi
derm
idis
(not
S. a
ureu
s)O
G
repa
floxa
cin
5 µg
≤
1415
-17
≥18
≥4
≤1
OSp
arflo
xaci
n 5
µg
≤15
16-1
8 ≥
19≥
2 ≤
0.5
Inv.
Fler
oxac
in5
µg
≤15
16-1
8≥
19
≥8
≤2
NIT
RO
FUR
AN
TOIN
S U
Nitr
ofur
anto
in30
0 µg
≤14
15
-16
≥17
≥12
8≤
32
January 2005 Vol. 25 No. 1
©Clinical and Laboratory Standards Institute. All rights reserved.50
Tabl
e 2C
Stap
hylo
cocc
ussp
p.M
2-D
isk
Diff
usio
n
Test
/Rep
ort
Gro
up
Ant
imic
robi
al
Age
nt
Dis
k C
onte
nt
Zone
Dia
met
er,
Nea
rest
Who
le m
m
Equi
vale
nt M
ICB
reak
poin
ts (µµ
g/m
L)
Com
men
ts
R
I S
R
S LI
NC
OSA
MID
ES
B
Clin
dam
ycin
2 µg
≤
14
15-2
0 ≥
21
≥4
≤0.
5(2
7) M
acro
lide-
resi
stan
t is
olat
es o
f S.
aur
eus
and
coag
ulas
e-ne
gativ
e St
aphy
loco
ccus
spp.
may
hav
e co
nstit
utiv
e or
indu
cibl
ere
sist
ance
to c
linda
myc
in [m
ethy
latio
n of
the
23S
rR
NA
enco
ded
by
the
erm
gene
al
so
refe
rred
to
as
M
LSB
(mac
rolid
e,lin
coso
mid
e, a
nd t
ype
B s
trept
ogra
min
) re
sist
ance
] or
may
be
resi
stan
t on
ly t
o m
acro
lides
(ef
flux-
mec
hani
sm e
ncod
ed b
y th
em
srA
gene
). I
nduc
ible
clin
dam
ycin
res
ista
nce
can
be d
etec
ted
usin
g a
disk
app
roxi
mat
ion
test
by
plac
ing
a 2-
µg c
linda
myc
indi
sk f
rom
15
mm
to
26 m
m a
way
fro
m t
he e
dge
of a
15-
µger
ythr
omyc
in d
isk
as p
art o
f the
nor
mal
dis
k di
ffusi
on p
roce
dure
.Fo
llow
ing
incu
batio
n, o
rgan
ism
s th
at d
o no
t sho
w fl
atte
ning
of t
hecl
inda
myc
in z
one
shou
ld b
e re
porte
d as
clin
dam
ycin
sus
cept
ible
.O
rgan
ism
s th
at s
how
flat
teni
ng o
f the
clin
dam
ycin
zon
e ad
jace
ntto
the
ery
thro
myc
in d
isk
(ref
erre
d to
as
a “D
” zo
ne)
indi
cate
indu
cibl
e cl
inda
myc
in
resi
stan
ce.
Suc
h is
olat
es
shou
ld
bere
porte
d as
“cl
inda
myc
in r
esis
tant
.” A
com
men
t tha
t “Th
is is
olat
eis
pre
sum
ed t
o be
res
ista
nt b
ased
on
dete
ctio
n of
ind
ucib
lecl
inda
myc
in re
sist
ance
. Clin
dam
ycin
may
stil
l be
effe
ctiv
e in
som
epa
tient
s.”
may
be
in
clud
ed.
For
qual
ity
cont
rol/q
ualit
yas
sess
men
t rec
omm
enda
tions
, ref
er to
Tab
le 3
.S
ee c
omm
ent (
23).
FOLA
TE P
ATH
WAY
INH
IBIT
OR
SB
Trim
etho
prim
-sul
fam
etho
xazo
le
1.25
/23.
75 µ
g≤
10
11-1
5 ≥
16
≥8/
152
≤2/
38
U
Sul
fona
mid
es
250
or 3
00 µ
g ≤
12
13-1
6 ≥
17
≥35
0≤
100
(28)
The
sul
fisox
azol
e di
sk c
an b
e us
ed to
rep
rese
nt a
ny o
f the
curr
ently
ava
ilabl
e su
lfona
mid
e pr
epar
atio
ns.
U
Trim
etho
prim
5
µg
≤10
11
-15
≥16
≥16
≤
4 PH
ENIC
OLS
CC
hlor
amph
enic
ol30
µg
≤12
13
-17
≥18
≥32
≤8
See
com
men
t (23
).
AN
SAM
YCIN
SC
R
ifam
pin
5 µg
≤16
17-1
9≥
20≥
4≤
1(2
9)R
x:R
ifam
pin
shou
ld n
ot b
e us
ed a
lone
for c
hem
othe
rapy
.ST
REP
TOG
RA
MIN
S
CQ
uinu
pris
tin-d
alfo
pris
tin15
µg
≤15
16
-18
≥19
≥
4≤
1O
XAZO
LID
INO
NES
BLi
nezo
lid30
µg
- -
≥21
- ≤
4S
ee c
omm
ent (
6).
Tabl
e 2C
. (C
ontin
ued)
For Use With M2-A8–Disk Diffusion M100-S15
51©Clinical and Laboratory Standards Institute. All rights reserved.
Table 2C. (Continued)
Disk Diffusion Testa for Prediction of mecA-mediated Resistance in Staphylococci
Antimicrobial Agent
(Disk Content)
Organism Group Zone Diameter,Nearest Whole mm
Comments
Cefoxitin (30 µg) S. aureus and S.lugdunensis
≤ 19 ≥ 20 (30) S. aureus for which cefoxitindisk diffusion zones are ≤ 19 mmshould be reported as oxacillinresistant. Those for whichcefoxitin zones are ≥ 20 mmshould be reported as oxacillinsusceptible.
Coagulase-negativestaphylococci exceptS. lugdunensis
≤ 24 ≥ 25 (31) Coagulase-negativestaphylococci for which cefoxitindisk diffusion zones are ≤ 24 mmshould be reported as oxacillinresistant. Those for whichcefoxitin zones are ≥ 25 mmshould be reported as oxacillinsusceptible.
a Use standard disk diffusion testing conditions and incubate for 24 hours; however, results may be reported after 18hours incubation if resistant. Read the cefoxitin disk test using reflected light.
Tabl
e 2C
Stap
hylo
cocc
ussp
p.M
2-D
isk
Diff
usio
n
January 2005 Vol. 25 No. 1
Tabl
e 2D
Ente
roco
ccus
spp.
M2-
Dis
k D
iffus
ion
52 ©Clinical and Laboratory Standards Institute. All rights reserved.
Tabl
e 2D
. Zo
ne D
iam
eter
Inte
rpre
tive
Stan
dard
s an
d Eq
uiva
lent
Min
imal
Inhi
bito
ry C
once
ntra
tion
(MIC
) Bre
akpo
ints
forE
nter
ococ
cus
spp.
Test
ing
Con
ditio
ns
Med
ium
:M
uelle
r-H
into
n ag
arIn
ocul
um:
Gro
wth
m
etho
d or
di
rect
co
lony
su
spen
sion
,eq
uiva
lent
to a
0.5
McF
arla
nd s
tand
ard
Incu
batio
n:35
°C
±2
degr
ees;
am
bien
t air;
16
to 1
8 ho
urs;
24
hour
s fo
r van
com
ycin
Min
imal
QC
Rec
omm
enda
tions
(See
Tab
le 3
for a
ccep
tabl
e Q
C ra
nges
.)
Stap
hylo
cocc
us a
ureu
s AT
CC
® 2
5923
Gen
eral
Com
men
ts
(1)
WA
RN
ING
:Fo
r En
tero
cocc
us
spp.
, ce
phal
ospo
rins,
am
inog
lyco
side
s (e
xcep
t fo
r hi
gh-le
vel
resi
stan
ce
scre
enin
g),
clin
dam
ycin
, an
d tri
met
hopr
im-
sulfa
met
hoxa
zole
may
app
ear a
ctiv
e in
vitr
obu
t are
not
effe
ctiv
e cl
inic
ally,
and
isol
ates
sho
uld
not b
e re
porte
d as
sus
cept
ible
.
(2)
Syn
ergy
bet
wee
n am
pici
llin,
pen
icill
in, o
r van
com
ycin
and
an
amin
ogly
cosi
de c
an b
e pr
edic
ted
for e
nter
ococ
ci b
y us
ing
a hi
gh-le
vel a
min
ogly
cosi
de (g
enta
mic
inan
d st
rept
omyc
in)
scre
enin
g te
st. O
ther
am
inog
lyco
side
s ne
ed n
ot b
e te
sted
, bec
ause
thei
r ac
tiviti
es a
gain
st e
nter
ococ
ci a
re n
ot s
uper
ior
to g
enta
mic
in a
ndst
rept
omyc
in.
(3)
Bec
ause
of l
imite
d al
tern
ativ
es, c
hlor
amph
enic
ol, e
ryth
rom
ycin
, tet
racy
clin
e (o
r dox
ycyc
line
or m
inoc
yclin
e), a
nd ri
fam
pin
may
be
used
for v
anco
myc
in-r
esis
tant
ente
roco
cci (
VR
E),
and
cons
ulta
tion
with
an
infe
ctio
us d
isea
se p
ract
ition
er is
reco
mm
ende
d.
(4)
For
som
e or
gani
sm/a
ntim
icro
bial
age
nt c
ombi
natio
ns,
the
abse
nce
of r
esis
tant
str
ains
pre
clud
es d
efin
ing
any
resu
lts c
ateg
orie
s ot
her
than
“sus
cept
ible
.” F
or s
trai
ns y
ield
ing
resu
lts s
ugge
stiv
e of
a “
nons
usce
ptib
le”
cate
gory
, org
anis
m id
entif
icat
ion
and
antim
icro
bial
sus
cept
ibili
ty te
stre
sults
sho
uld
be c
onfir
med
. Sub
sequ
ently
, the
isol
ates
sho
uld
be s
aved
and
sub
mitt
ed to
a r
efer
ence
labo
rato
ry th
at w
ill c
onfir
m r
esul
ts u
sing
aC
LSI/N
CC
LS r
efer
ence
dilu
tion
met
hod.
NO
TE:
Info
rmat
ion
in b
oldf
ace
type
is c
onsi
dere
d te
ntat
ive
for o
ne y
ear.
For Use With M2-A8–Disk Diffusion M100-S15
53©Clinical and Laboratory Standards Institute. All rights reserved.
Tabl
e 2D
Ente
roco
ccus
spp.
M2-
Dis
k D
iffus
ion
Tabl
e 2D
. (C
ontin
ued)
Test
/Rep
ort
Gro
up
Ant
imic
robi
al
Age
nt
Dis
k C
onte
nt
Zone
Dia
met
er,
Nea
rest
Who
le m
m
Equi
vale
nt M
ICB
reak
poin
ts (µµ
g/m
L)
Com
men
tsR
I
S R
S
PEN
ICIL
LIN
SA A
Pen
icill
in o
r am
pici
llin
10 u
nits
10 µ
g≤
14≤
16
- - ≥
15≥
17≥
16≥
16
≤8
≤8
(5)
Am
pici
llin
is t
he c
lass
rep
rese
ntat
ive
for
ampi
cilli
n an
dam
oxic
illin
. A
mpi
cilli
n re
sults
m
ay
be
used
to
pr
edic
tsu
scep
tibili
ty
to
amox
icill
in-c
lavu
lani
c ac
id,
ampi
cilli
n-su
lbac
tam
, pi
pera
cilli
n,
and
pipe
raci
llin-
tazo
bact
am
amon
gno
n-β-
lact
amas
e-pr
oduc
ing
ente
roco
cci.
(6)
P
enic
illin
su
scep
tibili
ty
may
be
us
ed
to
pred
ict
the
susc
eptib
ility
to
am
pici
llin,
am
oxic
illin
, am
pici
llin-
sulb
acta
m,
amox
icill
in-c
lavu
lani
c ac
id,
pipe
raci
llin,
an
d pi
pera
cilli
n-ta
zoba
ctam
fo
r no
n-β-
lact
amas
e-pr
oduc
ing
ente
roco
cci.
Am
pici
llin
susc
eptib
ility
ca
n be
us
ed
to
pred
ict
imip
enem
susc
eptib
ility
, pr
ovid
ed
the
spec
ies
is
conf
irmed
to
be
E.
faec
alis
.
(7)
Rx:
The
“sus
cept
ible
” ca
tego
ry f
or p
enic
illin
or
ampi
cilli
nim
plie
s th
e ne
ed fo
r hig
h-do
se th
erap
y fo
r ser
ious
ent
eroc
occa
lin
fect
ions
. E
nter
ococ
cal
endo
card
itis
requ
ires
com
bine
dth
erap
y w
ith h
igh-
dose
pen
icill
in o
r hi
gh-d
ose
ampi
cilli
n, o
rva
ncom
ycin
or
teic
opla
nin
plus
gen
tam
icin
or
stre
ptom
ycin
for
bact
eric
idal
act
ion.
(8)
B
ecau
se
ampi
cilli
n or
pe
nici
llin
resi
stan
ce
amon
gen
tero
cocc
i du
e to
β-
lact
amas
e pr
oduc
tion
is
not
relia
bly
dete
cted
us
ing
rout
ine
disk
or
di
lutio
n m
etho
ds,
a di
rect
,ni
troce
fin-b
ased
β-la
ctam
ase
test
is
reco
mm
ende
d fo
r bl
ood
and
cere
bros
pina
l flu
id i
sola
tes.
Apo
sitiv
e β-
lact
amas
e te
stpr
edic
ts r
esis
tanc
e to
pen
icill
in,
as w
ell
as a
min
o-,
carb
oxy-
,an
d ur
eido
peni
cilli
ns.
GLY
CO
PEPT
IDES
B
Vanc
omyc
in
30 µ
g ≤
14
15-1
6≥
17
≥32
≤
4 (9
) W
hen
test
ing
vanc
omyc
in a
gain
st e
nter
ococ
ci,
plat
essh
ould
be
held
a fu
ll 24
hou
rs a
nd e
xam
ined
usi
ng tr
ansm
itted
light
; the
pre
senc
e of
a h
aze
or a
ny g
row
th w
ithin
the
zone
of
inhi
bitio
n in
dica
tes
resi
stan
ce.
Org
anis
ms
with
int
erm
edia
tezo
nes
shou
ld b
e te
sted
by
an M
IC m
etho
d as
des
crib
ed i
nC
LSI/N
CC
LS d
ocum
ent
M7.
See
als
o th
e va
ncom
ycin
aga
rsc
reen
test
des
crib
ed in
M7,
Tab
le 2
D.
See
com
men
ts (2
) and
(7).
Inv.
Teic
opla
nin
30 µ
g≤
1011
-13
≥14
≥32
≤8
See
com
men
ts (2
) and
(7).
LIPO
PEPT
IDES
BD
apto
myc
in30
µµg
--
≥≥11
-≤≤
4 Se
e co
mm
ent (
4).
MA
CR
OLI
DES
C
Ery
thro
myc
in15
µg
≤13
14
-22
≥23
≥8
≤0.
5(1
0) N
ot ro
utin
ely
repo
rted
on is
olat
es fr
om th
e ur
inar
y tra
ct.
January 2005 Vol. 25 No. 1
Tabl
e 2D
Ente
roco
ccus
spp.
M2-
Dis
k D
iffus
ion
54 ©Clinical and Laboratory Standards Institute. All rights reserved.
Tabl
e 2D
. (C
ontin
ued)
Test
/Rep
ort
Gro
up
Ant
imic
robi
al
Age
nt
Dis
k C
onte
nt
Zone
Dia
met
er,
Nea
rest
Who
le m
m
Equi
vale
nt M
ICB
reak
poin
ts (µµ
g/m
L)
Com
men
tsR
I
S R
S
TETR
AC
YCLI
NES
Se
e co
mm
ent (
3).
CTe
tracy
clin
e30
µg
≤14
15-1
8≥
19≥
16≤
4 (1
1)
Org
anis
ms
that
ar
e su
scep
tible
to
tetra
cycl
ine
are
also
con
side
red
susc
eptib
le t
odo
xycy
clin
e an
d m
inoc
yclin
e.
How
ever
, so
me
orga
nism
s th
at a
re in
term
edia
te o
r re
sist
ant
tote
tracy
clin
e m
ay b
e su
scep
tible
to
doxy
cycl
ine
or m
inoc
yclin
e or
bot
h.O
D
oxyc
yclin
e30
µg
≤12
13-1
5≥
16≥
16≤
4 O
M
inoc
yclin
e30
µg
≤14
15
-18
≥19
≥16
≤4
FLU
OR
OQ
UIN
OLO
NES
U U U
Cip
roflo
xaci
nLe
voflo
xaci
nN
orflo
xaci
n
5 µg
5 µg
10 µ
g
≤15
≤13
≤12
16-2
014
-16
13-1
6
≥21
≥17
≥17
≥4
≥
8≥
16
≤1
≤2
≤4
OG
atifl
oxac
in5
µg
≤14
15-1
7 ≥
18
≥8
≤2
(12)
Thi
s br
eakp
oint
app
lies
to u
rinar
y tra
ctis
olat
es o
nly.
NIT
RO
FUR
AN
TOIN
SU
N
itrof
uran
toin
30
0 µg
≤
14
15-1
6 ≥
17
≥12
8≤
32
AN
SAM
YCIN
SC
R
ifam
pin
5 µg
≤
16
17-1
9≥
20≥
4 ≤
1 (1
3)
Rx:
R
ifam
pin
shou
ld n
ot b
e us
ed a
lone
for c
hem
othe
rapy
.
See
com
men
t (3)
.
FOSF
OM
YCIN
SU
Fo
sfom
ycin
20
0 µg
≤
12
13-1
5≥
16
≥25
6≤
64(1
4)
For
use
with
E. fa
ecal
ison
ly. T
he 2
00-µ
gfo
sfom
ycin
dis
k co
ntai
ns 5
0 µg
of
gluc
ose-
6-ph
osph
ate.
PH
ENIC
OLS
CC
hlor
amph
enic
ol
30 µ
g≤
12
13-1
7 ≥
18
≥32
≤8
See
com
men
t (3)
.S
ee c
omm
ent (
10).
STR
EPTO
GR
AM
INS
B
Qui
nupr
istin
-dal
fopr
istin
15 µ
g≤
1516
-18
≥19
≥
4≤
1O
XAZO
LID
INO
NES
BLi
nezo
lid30
µg
≤20
21-2
2≥
23
≥8
≤2
For Use With M2-A8–Disk Diffusion M100-S15
55©Clinical and Laboratory Standards Institute. All rights reserved.
Disk Diffusion Screening Tests for High-Level Aminoglycoside Resistance (HLAR)a
Test/ResultGroup
AntimicrobialAgent
DiskContent
Zone Diameter,Nearest Whole mm
Equivalent MICBreakpoints (µµg/mL) Comments
R I S R SC Gentamicin
(HLAR) 120 µg 6 7-9 ≥ 10 > 500 ≤ 500 (15) If the zone is 7 to 9 mm, the
test is inconclusive, and an agardilution or broth microdilutionscreen test should be performedto confirm resistance. Seecomments (2) and (7).
C Streptomycin(HLAR)
300 µg 6 7-9 ≥ 10 - - (16) MIC correlates forstreptomycin broth microdilutionare resistant >1000 µg/mL andfor agar dilution > 2000 µg/mL.See comments (2), (7), and (15).
Footnote
a. For QC of HLAR screen tests, use Enterococcus faecalis ATCC® 29212 (see Table 3, Footnote f [Disk Testing] foracceptable QC ranges).
See M7,Table 2D (MIC Testing) which summarizes additional screening tests for vancomycin, high-levelaminoglycoside resistance, and supplemental tests for identification that may be helpful for vancomycin-resistant enterococci.
Table 2D. (Continued)
Tabl
e 2D
Ente
roco
ccus
spp.
M2-
Dis
k D
iffus
ion
January 2005 Vol. 25 No. 1
Tabl
e 2E
Hae
mop
hilu
sspp
.M
2-D
isk
Diff
usio
n
56©Clinical and Laboratory Standards Institute. All rights reserved.
Tabl
e 2E
. Zo
ne D
iam
eter
Inte
rpre
tive
Stan
dard
s an
d Eq
uiva
lent
Min
imal
Inhi
bito
ry C
once
ntra
tion
(MIC
) Bre
akpo
ints
for H
aem
ophi
lus
spp.
Test
ing
Con
ditio
ns
Med
ium
:H
aem
ophi
lus
Test
Med
ium
(HTM
)In
ocul
um:
Dire
ct c
olon
y su
spen
sion
, equ
ival
ent t
o a
0.5
McF
arla
nd s
tand
ard
Incu
batio
n:35
°C
±2
degr
ees;
5%
CO
2; 1
6 to
18
hour
s
Min
imal
QC
Rec
omm
enda
tions
(See
Tab
le 3
Afo
r acc
epta
ble
QC
rang
es.)
Hae
mop
hilu
s in
fluen
zae
ATC
C®
4924
7H
aem
ophi
lus
influ
enza
e AT
CC
®49
766
Esch
eric
hia
coli
ATC
C®
352
18 (w
hen
test
ing
amox
icill
in-c
lavu
lani
c ac
id)
Test
/Rep
ort
Gro
up
Ant
imic
robi
al
Age
nt
Dis
k C
onte
nt
Zone
Dia
met
er,
Nea
rest
Who
le m
m
Equi
vale
nt M
ICB
reak
poin
ts (µµ
g/m
L)
Com
men
tsR
I
S R
S
PEN
ICIL
LIN
SA
Am
pici
llin
10 µ
g≤
1819
-21
≥22
≥4
≤1
(5)
The
resu
lts o
f am
pici
llin
susc
eptib
ility
tes
ts s
houl
d be
used
to p
redi
ct th
e ac
tivity
of a
mox
icill
in. I
n m
ost c
ases
, adi
rect
β-la
ctam
ase
test
can
pro
vide
a r
apid
mea
ns o
fde
tect
ing
ampi
cilli
n an
d am
oxic
illin
resi
stan
ce. T
he m
ajor
ityof
isol
ates
of
H.
influ
enza
e th
at a
re r
esis
tant
to
ampi
cilli
nan
d am
oxic
illin
pro
duce
a T
EM
-type
β-la
ctam
ase.
(6)
R
are
β-la
ctam
ase-
nega
tive,
am
pici
llin-
resi
stan
t(B
LNA
R)
stra
ins
of H
. in
fluen
zae
shou
ld b
e co
nsid
ered
resi
stan
t to
am
oxic
illin
-cla
vula
nic
acid
, am
pici
llin-
sulb
acta
m,
cefa
clor
, ce
feta
met
, ce
foni
cid,
ce
fpro
zil,
cefu
roxi
me,
an
d lo
raca
rbef
de
spite
ap
pare
nt
in
vitro
susc
eptib
ility
of s
ome
BLN
AR
stra
ins
to th
ese
agen
ts.
Gen
eral
Com
men
ts
(1)O
nly
resu
lts o
f tes
ting
with
am
pici
llin,
one
of t
he th
ird-g
ener
atio
n ce
phal
ospo
rins,
chl
oram
phen
icol
, and
mer
open
em s
houl
d be
repo
rted
rout
inel
y w
ith C
SF
isol
ates
of H
aem
ophi
lus
influ
enza
e.
(2)A
mox
icill
in-c
lavu
lani
c ac
id, a
zith
rom
ycin
, cla
rithr
omyc
in, c
efac
lor,
cefp
rozi
l, lo
raca
rbef
, cef
dini
r, ce
fixim
e, c
efpo
doxi
me,
and
cef
urox
ime
axet
il ar
e or
al a
gent
s th
atm
ay b
e us
ed a
s em
piric
ther
apy
for r
espi
rato
ry tr
act i
nfec
tions
due
to H
aem
ophi
lus
spp.
The
resu
lts o
f sus
cept
ibili
ty te
sts
with
thes
e an
timic
robi
al a
gent
s ar
e of
ten
not u
sefu
l for
man
agem
ent o
f ind
ivid
ual p
atie
nts.
How
ever
, sus
cept
ibili
ty te
stin
g of
Hae
mop
hilu
ssp
p. w
ith th
ese
com
poun
ds m
ay b
e ap
prop
riate
for s
urve
illan
ceor
epi
dem
iolo
gic
stud
ies.
(3)T
o m
ake
HTM
: a fr
esh
hem
atin
sto
ck s
olut
ion
is p
repa
red
by d
isso
lvin
g 50
mg
of h
emat
in p
owde
r in
100
mL
of 0
.01
mol
/LN
aOH
with
hea
t and
stir
ring
until
the
pow
der
is t
horo
ughl
y di
ssol
ved.
The
n 30
mL
of t
he h
emat
in s
tock
sol
utio
n is
add
ed t
o 1
Lof
Mue
ller-
Hin
ton
agar
with
5 g
of
yeas
t ex
tract
als
o ad
ded.
Afte
rau
tocl
avin
g an
d co
olin
g, 3
mL
of a
n N
AD
sto
ck s
olut
ion
(50
mg
of N
AD
dis
solv
ed in
10
mL
of d
istil
led
wat
er, f
ilter
ste
riliz
ed) i
s ad
ded
asep
tical
ly.
(4) F
or s
ome
orga
nism
/ant
imic
robi
al a
gent
com
bina
tions
, th
e ab
senc
e of
res
ista
nt s
train
s pr
eclu
des
defin
ing
any
resu
lts c
ateg
orie
s ot
her
than
“su
scep
tible
.” F
orst
rain
s yi
eldi
ng r
esul
ts s
ugge
stiv
e of
a “
nons
usce
ptib
le”
cate
gory
, or
gani
sm i
dent
ifica
tion
and
antim
icro
bial
sus
cept
ibili
ty t
est
resu
lts s
houl
d be
con
firm
ed.
Sub
sequ
ently
, the
isol
ates
sho
uld
be s
aved
and
sub
mitt
ed to
a re
fere
nce
labo
rato
ry th
at w
ill c
onfir
m re
sults
usi
ng a
CLS
I/NC
CLS
refe
renc
e di
lutio
n m
etho
d .
NO
TE:I
nfor
mat
ion
in b
oldf
ace
type
is c
onsi
dere
d te
ntat
ive
for o
ne y
ear.
For Use With M2-A8–Disk Diffusion M100-S15
57
Tabl
e 2E
Hae
mop
hilu
sspp
.M
2-D
isk
Diff
usio
n
©Clinical and Laboratory Standards Institute. All rights reserved.
Tabl
e 2E
. (C
ontin
ued)
Test
/Rep
ort
Gro
up
Ant
imic
robi
al
Age
nt
Dis
k C
onte
nt
Zone
Dia
met
er,
Nea
rest
Who
le m
m
Equi
vale
nt M
ICB
reak
poin
ts (µµ
g/m
L)
Com
men
tsR
I
S R
S
ββ -LA
CTA
M/ββ
-LA
CTA
MA
SE IN
HIB
ITO
R C
OM
BIN
ATIO
NS
See
com
men
t (6)
.O O
Am
oxic
illin
-cla
vula
nic
acid
Am
pici
llin-
sulb
acta
m20
/10
µg10
/10
µg≤
19≤
19- -
≥20
≥20
≥8/
4≥
4/2
≤4/
2≤
2/1
CEP
HEM
S (P
AR
ENTE
RA
L) (
Incl
udin
g ce
phal
ospo
rins
I, II,
III,
and
IV. P
leas
e re
fer
to G
loss
ary
I.)S
ee c
omm
ent (
6).
B B B B
Cef
otax
ime
orce
ftazi
dim
e or
cefti
zoxi
me
orce
ftria
xone
30 µ
g30
µg
30 µ
g30
µg
- - - -
- - - -
≥26
≥26
≥26
≥26
- - - -
≤2
≤2
≤2
≤2
See
com
men
t (4)
.
B
Cef
urox
ime
sodi
um
(par
ente
ral)
30 µ
g≤
1617
-19
≥20
≥16
≤4
C
Cef
onic
id30
µg
≤16
17-1
9≥
20≥
16≤
4O
Cef
epim
e30
µg
- -
≥26
- ≤
2S
ee c
omm
ent (
4).
CEP
HEM
S (O
RA
L)S
ee c
omm
ent (
6).
C C C
Cef
aclo
r or
cefp
rozi
l or
lora
carb
ef
30 µ
g30
µg
30 µ
g
≤16
≤14
≤15
17-1
915
-17
16-1
8
≥20
≥18
≥19
≥32
≥32
≥32
≤8
≤8
≤8
C C C
Cef
dini
r or
cefix
ime
orce
fpod
oxim
e
5 µg
5 µg
10 µ
g
- - -
- - -
≥20
≥21
≥21
- - -
≤1
≤1
≤2
See
com
men
t (4)
.
CC
efur
oxim
e ax
etil
(ora
l)30
µg
≤16
17-1
9≥
20≥
16≤
4O
Cef
tibut
en30
µg
- -
≥28
- ≤
2S
ee c
omm
ent (
4).
Inv.
Cef
etam
et10
µg
≤14
15-1
7≥
18≥
16≤
4C
AR
BA
PEN
EMS
BM
erop
enem
10 µ
g-
- ≥
20-
≤0.
5S
ee c
omm
ent (
4).
C C
Erta
pene
m o
r im
ipen
em
10 µ
g10
µg
- -- -
≥19
≥16
- - ≤
0.5
≤4
See
com
men
t (4)
.
MO
NO
BA
CTA
MS
CA
ztre
onam
30 µ
g-
- ≥
26-
≤2
See
com
men
t (4)
.M
AC
RO
LID
ESC C
Azi
thro
myc
in o
rcl
arith
rom
ycin
15 µ
g15
µg
-≤
10-
11-1
2≥
12≥
13-
≥32
≤4
≤8
See
com
men
t (4)
.
KET
OLI
DES
CTe
lithr
omyc
in15
µg
≤11
12-1
4≥
15≥
16≤
4TE
TRA
CYC
LIN
ESC
Tetra
cycl
ine
30 µ
g≤
2526
-28
≥29
≥8
≤2
(7)
Org
anis
ms
that
are
sus
cept
ible
to te
tracy
clin
e ar
e al
soco
nsid
ered
sus
cept
ible
to d
oxyc
yclin
e an
d m
inoc
yclin
e.
January 2005 Vol. 25 No. 1
Tabl
e 2E
Hae
mop
hilu
sspp
.M
2-D
isk
Diff
usio
n
58©Clinical and Laboratory Standards Institute. All rights reserved.
Tabl
e 2E
. (C
ontin
ued)
Test
/Rep
ort
Gro
up
Ant
imic
robi
al
Age
nt
Dis
k C
onte
nt
Zone
Dia
met
er,
Nea
rest
Who
le m
m
Equi
vale
nt M
ICB
reak
poin
ts (µµ
g/m
L)
Com
men
ts
R
I S
R
S FL
UO
RO
QU
INO
LON
ES
C C C C C C C
Cip
roflo
xaci
n or
gatif
loxa
cin
orle
voflo
xaci
n or
lom
eflo
xaci
n or
mox
iflox
acin
or
oflo
xaci
nG
emifl
oxac
in
5 µg
5 µg
5 µg
10 µ
g5
µg5
µg5
µg
- - - - - - -
- - - - - - -
≥21
≥18
≥17
≥22
≥18
≥16
≥18
- - - - - - -
≤1
≤1
≤2
≤2
≤1
≤2
≤0.
12
See
com
men
t (4)
.
OG
repa
floxa
cin
5 µg
- -
≥24
- ≤
0.5
OTr
ovaf
loxa
cin
10 µ
g-
- ≥
22-
≤1
Inv.
Fler
oxac
in
5 µg
- -
≥19
-≤
2
FOLA
TE P
ATH
WAY
INH
IBIT
OR
SA
Trim
etho
prim
-su
lfam
etho
xazo
le1.
25/2
3.75
µg
≤10
11-1
5≥
16≥
4/76
≤0.
5/9.
5
PHEN
ICO
LS
BC
hlor
amph
enic
ol30
µg
≤25
26-2
8≥
29≥
8≤
2A
NSA
MYC
INS
CR
ifam
pin
5 µg
≤16
17-1
9≥
20≥
4 ≤
1
For Use With M2-A8–Disk Diffusion M100-S15
59©Clinical and Laboratory Standards Institute. All rights reserved.
This page is intentionally left blank.
January 2005 Vol. 25 No. 1
60
Tabl
e 2F
Nei
sser
ia g
onor
rhoe
aeM
2-D
isk
Diff
usio
n
©Clinical and Laboratory Standards Institute. All rights reserved.
Tabl
e 2F
. Zo
ne D
iam
eter
Inte
rpre
tive
Stan
dard
s an
d Eq
uiva
lent
Min
imal
Inhi
bito
ry C
once
ntra
tion
(MIC
) Bre
akpo
ints
for N
eiss
eria
gon
orrh
oeae
Test
ing
Con
ditio
ns
Med
ium
:G
C a
gar b
ase
and
1% d
efin
ed g
row
th s
uppl
emen
t.
The
use
of a
cys
tein
e-fre
e gr
owth
sup
plem
ent i
sno
t req
uire
d fo
r dis
k di
ffusi
on te
stin
g.In
ocul
um:
Dire
ct c
olon
y su
spen
sion
, equ
ival
ent t
o a
0.5
McF
arla
nd s
tand
ard.
Incu
batio
n:35
°C
±2
degr
ees;
5%
CO
2; 2
0 to
24
hour
s
Min
imal
QC
Rec
omm
enda
tions
(See
Tab
le 3
Afo
r acc
epta
ble
QC
rang
es.)
Nei
sser
ia g
onor
rhoe
aeAT
CC
®49
226
Gen
eral
Com
men
ts
(1)
For N
. gon
orrh
oeae
, an
inte
rmed
iate
resu
lt fo
r an
antim
icro
bial
age
nt in
dica
tes
eith
er a
tech
nica
l pro
blem
that
sho
uld
be re
solv
ed b
y re
peat
test
ing
or a
lack
of
clin
ical
exp
erie
nce
in tr
eatin
g or
gani
sms
with
thes
e zo
nes.
The
latte
r see
ms
to b
e th
e ca
se fo
r cef
met
azol
e, c
efot
etan
, cef
oxiti
n, a
nd s
pect
inom
ycin
. Stra
ins
with
inte
rmed
iate
zon
es w
ith th
e ot
her a
gent
s ha
ve a
doc
umen
ted
low
er c
linic
al c
ure
rate
(85
to 9
5%) c
ompa
red
to >
95%
for s
usce
ptib
le s
train
s.
(2)
Dis
k di
ffusi
on te
sts
with
am
pici
llin,
pen
icill
in, a
nd ri
fam
pin
for N
eiss
eria
men
ingi
tidis
are
unre
liabl
e. M
inim
al in
hibi
tory
con
cent
ratio
n (M
IC) t
ests
sho
uld
be u
sed
for t
hese
org
anis
ms.
(3)
The
reco
mm
ende
d m
ediu
m fo
r tes
ting
N. g
onor
rhoe
aeco
nsis
ts o
f GC
aga
r to
whi
ch a
1%
def
ined
gro
wth
sup
plem
ent (
1.1
g L-
cyst
eine
, 0.0
3 g
guan
ine
HC
L, 3
mg
thia
min
e H
CL,
13
mg
PAB
A, 0
.01
g B
12, 0
.1 g
coc
arbo
xyla
se, 0
.25
g N
AD
, 1 g
ade
nine
, 10
g L-
glut
amin
e, 1
00 g
glu
cose
, 0.0
2 g
ferr
ic n
itrat
e [in
1 L
H2O
])is
add
ed a
fter a
utoc
lavi
ng.
(4)
For
som
e or
gani
sm/a
ntim
icro
bial
age
nt c
ombi
natio
ns,
the
abse
nce
of r
esis
tant
stra
ins
prec
lude
s de
finin
g an
y re
sults
cat
egor
ies
othe
r th
an “
susc
eptib
le.”
For
stra
ins
yiel
ding
res
ults
sug
gest
ive
of a
“no
nsus
cept
ible
” ca
tego
ry,
orga
nism
ide
ntifi
catio
n an
d an
timic
robi
al s
usce
ptib
ility
tes
t re
sults
sho
uld
be c
onfir
med
.S
ubse
quen
tly, t
he is
olat
es s
houl
d be
sav
ed a
nd s
ubm
itted
to a
refe
renc
e la
bora
tory
that
will
con
firm
resu
lts u
sing
a C
LSI/N
CC
LS re
fere
nce
dilu
tion
met
hod.
NO
TE:
Info
rmat
ion
in b
oldf
ace
type
is c
onsi
dere
d te
ntat
ive
for o
ne y
ear.
For Use With M2-A8–Disk Diffusion M100-S15
61
Tabl
e 2F
Nei
sser
ia g
onor
rhoe
aeM
2-D
isk
Diff
usio
n
©Clinical and Laboratory Standards Institute. All rights reserved.
Tabl
e 2F
. (C
ontin
ued)
Test
/Rep
ort
Gro
up
Ant
imic
robi
al
Age
nt
Dis
k C
onte
nt
Zone
Dia
met
er,
Nea
rest
Who
le m
m
Equi
vale
nt M
ICB
reak
poin
ts (µµ
g/m
L)
Com
men
tsR
I
S R
S
PEN
ICIL
LIN
SC
Pen
icill
in10
uni
ts≤
2627
-46
≥47
≥2
≤0.
06(5
)
Apo
sitiv
e β-
lact
amas
e te
st
pred
icts
resi
stan
ce
to
peni
cilli
n,
ampi
cilli
n,
and
amox
icill
in.
(6)
Aβ-
lact
amas
e te
st w
ill d
etec
t on
e fo
rm o
fpe
nici
llin
resi
stan
ce in
N. g
onor
rhoe
aean
d al
som
ay
be
used
to
pr
ovid
e ep
idem
iolo
gic
info
rmat
ion.
St
rain
s w
ith
chro
mos
omal
lym
edia
ted
resi
stan
ce c
an b
e de
tect
ed o
nly
byth
e di
sk d
iffus
ion
met
hod
or t
he a
gar
dilu
tion
MIC
met
hod.
(7)
Gon
ococ
ci w
ith 1
0-un
it pe
nici
llin
disk
zon
edi
amet
ers
of
≤19
mm
ar
e lik
ely
to
be
β-la
ctam
ase-
prod
ucin
g st
rain
s. H
owev
er,
the
β-la
ctam
ase
test
re
mai
ns
pref
erab
le
to
othe
rsu
scep
tibili
ty
met
hods
fo
r ra
pid,
ac
cura
tere
cogn
ition
of
this
pla
smid
-med
iate
d pe
nici
llin
resi
stan
ce.
CEP
HEM
S (P
AR
ENTE
RA
L) (I
nclu
ding
cep
halo
spor
ins
I, II,
III,
and
IV. P
leas
e re
fer
to G
loss
ary
I.)C C C
Cef
otax
ime
orce
ftizo
xim
e or
ceftr
iaxo
ne
30 µ
g30
µg
30 µ
g
- - -
- - -
≥31
≥38
≥35
- - -
≤0.
5≤
0.5
≤0.
25
See
com
men
t (4)
.
C C C C
Cef
met
azol
eC
efot
etan
C
efox
itin
Cef
urox
ime
sodi
um
(par
ente
ral)
30 µ
g30
µg
30 µ
g30
µg
≤27
≤19
≤23
≤25
28-3
220
-25
24-2
726
-30
≥33
≥26
≥28
≥31
≥8
≥8
≥8
≥4
≤2
≤2
≤2
≤1
OC
efep
ime
30 µ
g-
- ≥
31-
≤0.
5S
ee c
omm
ent (
4).
OC
efta
zidi
me
30 µ
g-
- ≥
31-
≤0.
5S
ee c
omm
ent (
4).
CEP
HEM
S (O
RA
L)C C
C
efix
ime
or
cefp
odox
ime
5 µg
10 µ
g- -
- - ≥
31≥
29- -
≤0.
25≤
0.5
See
com
men
t (4)
.
Inv.
C
efet
amet
10 µ
g -
- ≥
29-
≤0.
5S
ee c
omm
ent (
4).
TETR
AC
YCLI
NES
C
Tetra
cycl
ine
30 µ
g≤
3031
-37
≥38
≥2
≤0.
25(8
) G
onoc
occi
with
30-
µg te
tracy
clin
e di
sk z
one
diam
eter
s of
≤19
mm
usu
ally
indi
cate
a p
lasm
id-
med
iate
d te
tracy
clin
e-re
sist
ant
N.
gono
rrhoe
ae(T
RN
G)
isol
ate.
Th
ese
stra
ins
shou
ld
beco
nfirm
ed b
y a
dilu
tion
test
(M
IC ≥
16 µ
g/m
L).
Ple
ase
refe
r to
Tabl
e 2F
in M
7.
January 2005 Vol. 25 No. 1
62
Tabl
e 2F
Nei
sser
ia g
onor
rhoe
aeM
2-D
isk
Diff
usio
n
©Clinical and Laboratory Standards Institute. All rights reserved.
Tabl
e 2F
. (C
ontin
ued)
Test
/Rep
ort
Gro
up
Ant
imic
robi
al
Age
nt
Dis
k C
onte
nt
Zone
Dia
met
er,
Nea
rest
Who
le m
m
Equi
vale
nt M
ICB
reak
poin
ts (µµ
g/m
L)
Com
men
tsR
I
S R
S
FLU
OR
OQ
UIN
OLO
NES
C C C
Cip
roflo
xaci
n or
gatif
loxa
cin
orof
loxa
cin
5 µg
5 µg
5 µg
≤27
≤33
≤24
28-4
034
-37
25-3
0
≥41
≥38
≥31
≥1
≥0.
5≥
2
≤0.
06≤
0.12
≤0.
25
OE
noxa
cin
10 µ
g≤
3132
-35
≥36
≥2
≤0.
5O
Gre
paflo
xaci
n5
µg≤
2728
-36
≥37
≥1
≤0.
06O
Lom
eflo
xaci
n10
µg
≤26
27-3
7≥
38≥
2≤
0.12
OTr
ovaf
loxa
cin
10 µ
g-
-≥
34-
≤0.
25S
ee c
omm
ent (
4).
Inv.
Fler
oxac
in5
µg≤
2829
-34
≥35
≥1
≤0.
25A
MIN
OC
YCLI
TOLS
CSp
ectin
omyc
in10
0 µg
≤14
15-1
7≥
18≥
128
≤32
For Use With M2-A8–Disk Diffusion M100-S15
63©Clinical and Laboratory Standards Institute. All rights reserved.
This page is intentionally left blank.
January 2005 Vol. 25 No. 1
64
Tabl
e 2G
Stre
ptoc
occu
s pne
umon
iae
M2-
Dis
k D
iffus
ion
©Clinical and Laboratory Standards Institute. All rights reserved.
Tabl
e 2G
.Zo
ne D
iam
eter
Inte
rpre
tive
Stan
dard
s an
d Eq
uiva
lent
Min
imal
Inhi
bito
ry C
once
ntra
tion
(MIC
) Bre
akpo
ints
for
Stre
ptoc
occu
s pn
eum
onia
eTe
stin
g C
ondi
tions
Med
ium
:M
uelle
r-H
into
n ag
ar w
ith 5
% s
heep
blo
odIn
ocul
um:
Dire
ct c
olon
y su
spen
sion
, equ
ival
ent t
o a
0.5
McF
arla
nd s
tand
ard
Incu
batio
n:35
°C
±2
degr
ees;
5%
CO
2; 2
0 to
24
hour
s
Min
imal
QC
Rec
omm
enda
tions
(See
Tab
le 3
Afo
r acc
epta
ble
QC
rang
es.)
Stre
ptoc
occu
s pn
eum
onia
eAT
CC
® 4
9619
Test
/Rep
ort
Gro
up
Ant
imic
robi
al
Age
nt
Dis
k C
onte
nt
Zone
Dia
met
er,
Nea
rest
Who
le m
m
Equi
vale
nt M
ICB
reak
poin
ts (µµ
g/m
L)
Com
men
tsR
I
S R
S
PEN
ICIL
LIN
S(4
) Is
olat
es o
f pne
umoc
occi
with
oxa
cilli
n zo
ne s
izes
of ≥
20m
m a
re s
usce
ptib
le (M
IC ≤
0.06
µg/
mL)
to p
enic
illin
and
can
be
cons
ider
ed
susc
eptib
le
to
ampi
cilli
n,
amox
icill
in,
amox
icill
in-c
lavu
lani
c ac
id,
ampi
cilli
n-su
lbac
tam
, ce
facl
or,
cefd
inir,
cef
epim
e, c
efet
amet
, cef
ixim
e, c
efot
axim
e, c
efpr
ozil,
cefti
bute
n, c
eftri
axon
e, c
efur
oxim
e, c
efpo
doxi
me,
cef
tizox
ime,
erta
pene
m,
imip
enem
, lo
raca
rbef
, an
d m
erop
enem
fo
rap
prov
ed in
dica
tions
, and
thes
e ag
ents
nee
d no
t be
test
ed.
AP
enic
illin
1 µg
oxa
cilli
n-
- ≥
20-
≤0.
06(5
) P
enic
illin
, m
erop
enem
, an
d ce
fota
xim
e or
cef
triax
one
MIC
s sh
ould
be
dete
rmin
ed fo
r th
ose
isol
ates
with
oxa
cilli
nzo
ne s
izes
≤19
mm
, bec
ause
zon
es o
f ≤1
9 m
m o
ccur
with
peni
cilli
n-re
sist
ant,
inte
rmed
iate
, or
ce
rtain
su
scep
tible
stra
ins.
Isol
ates
sho
uld
not b
e re
porte
d as
pen
icill
in-r
esis
tant
or in
term
edia
te b
ased
sol
ely
on a
n ox
acill
in z
one
≤19
mm
.
Gen
eral
Com
men
ts
(1)
Am
oxic
illin
, am
pici
llin,
cef
epim
e, c
efot
axim
e, c
eftri
axon
e, c
efur
oxim
e, e
rtape
nem
, im
ipen
em, a
nd m
erop
enem
may
be
used
to tr
eat p
neum
ococ
cal i
nfec
tions
;ho
wev
er, r
elia
ble
disk
diff
usio
n su
scep
tibili
ty te
sts
with
thes
e ag
ents
do
not y
et e
xist
. The
ir in
vitr
oac
tivity
is b
est d
eter
min
ed u
sing
an
MIC
met
hod.
(2)
Pen
icill
in, c
efot
axim
e or
cef
triax
one,
and
mer
open
em s
houl
d be
test
ed b
y a
relia
ble
MIC
met
hod
(suc
h as
that
des
crib
ed in
CLS
I/NC
CLS
doc
umen
t M7)
and
repo
rted
rout
inel
y w
ith C
SF
isol
ates
of S
. pne
umon
iae.
Suc
h is
olat
es s
houl
d al
so b
e te
sted
aga
inst
van
com
ycin
usi
ng th
e M
IC o
r dis
k m
etho
d.
(3)
For s
ome
orga
nism
/ant
imic
robi
al a
gent
com
bina
tions
, the
abs
ence
of r
esis
tant
stra
ins
prec
lude
s de
finin
g an
y re
sults
cat
egor
ies
othe
r tha
n “s
usce
ptib
le.”
For
stra
ins
yiel
ding
res
ults
sug
gest
ive
of a
“no
nsus
cept
ible
” ca
tego
ry,
orga
nism
iden
tific
atio
n an
d an
timic
robi
al s
usce
ptib
ility
tes
t re
sults
sho
uld
be c
onfir
med
.S
ubse
quen
tly, t
he is
olat
es s
houl
d be
sav
ed a
nd s
ubm
itted
to a
refe
renc
e la
bora
tory
that
will
con
firm
resu
lts u
sing
a C
LSI/N
CC
LS re
fere
nce
dilu
tion
met
hod.
NO
TE:
Info
rmat
ion
in b
oldf
ace
type
is c
onsi
dere
d te
ntat
ive
for o
ne y
ear.
For Use With M2-A8–Disk Diffusion M100-S15
65
Tabl
e 2G
Stre
ptoc
occu
s pne
umon
iae
M2-
Dis
k D
iffus
ion
©Clinical and Laboratory Standards Institute. All rights reserved.
Tabl
e 2G
. (C
ontin
ued)
Test
/Rep
ort
Gro
up
Ant
imic
robi
al
Age
nt
Dis
k C
onte
nt
Zone
Dia
met
er,
Nea
rest
Who
le m
m
Equi
vale
nt M
ICB
reak
poin
ts (µµ
g/m
L)
Com
men
tsR
I
S R
S
GLY
CO
PEPT
IDES
BVa
ncom
ycin
30 µ
g-
- ≥
17-
≤1
(6)
No
S. p
neum
onia
est
rain
with
a v
anco
myc
inzo
ne d
iam
eter
<17
mm
has
bee
n ob
serv
ed;
subm
it su
ch s
train
s to
a re
fere
nce
labo
rato
ry.
MA
CR
OLI
DES
(7) S
usce
ptib
ility
and
resi
stan
ce to
azith
rom
ycin
, cla
rithr
omyc
in, a
nd d
irith
rom
ycin
can
be p
redi
cted
by
usin
g er
ythr
omyc
in.
(8)
Not
rou
tinel
y re
porte
d on
isol
ates
fro
m t
heur
inar
y tra
ct.
AE
ryth
rom
ycin
15 µ
g ≤
1516
-20
≥21
≥
1≤
0.25
OA
zith
rom
ycin
15
µg
≤13
14-1
7≥
18≥
2 ≤
0.5
OC
larit
hrom
ycin
15 µ
g≤
1617
-20
≥21
≥1
≤0.
25O
Diri
thro
myc
in15
µg
≤13
14
-17
≥18
≥2
≤0.
5K
ETO
LID
ESB
Telit
hrom
ycin
15 µ
g≤
1516
-18
≥19
≥
4 ≤
1TE
TRA
CYC
LIN
ESB
Tetra
cycl
ine
30 µ
g≤
1819
-22
≥23
≥8
≤2
(9)
Org
anis
ms
that
ar
e su
scep
tible
to
tetra
cycl
ine
are
also
con
side
red
susc
eptib
le t
odo
xycy
clin
e an
d m
inoc
yclin
e.FL
UO
RO
QU
INO
LON
ESB B B B B
B
Gat
iflox
acin
Gem
iflox
acin
Le
voflo
xaci
nM
oxifl
oxac
inSp
arflo
xaci
nO
floxa
cin
5 µg
5 µg
5 µg
5 µg
5 µg
5
µg
≤17
≤19
≤
13≤
14≤
15≤
12
18-2
020
-22
14-1
615
-17
16-1
813
-15
≥21
≥23
≥17
≥18
≥19
≥16
≥4
≥0.
5≥
8≥
4≥
2≥
8
≤1
≤0.
12≤
2≤
1≤
0.5
≤2
OG
repa
floxa
cin
5 µg
≤15
16-1
8≥
19≥
2≤
0.5
OTr
ovaf
loxa
cin
10 µ
g≤
1516
-18
≥19
≥4
≤1
FOLA
TE P
ATH
WAY
INH
IBIT
OR
SA
Trim
etho
prim
-su
lfam
etho
xazo
le1.
25/
23.7
5 µg
≤15
16-1
8≥
19≥
4/76
≤
0.5/
9.5
PHEN
ICO
LSC
Chl
oram
phen
icol
30
µg
≤20
- ≥
21≥
8≤
4S
ee c
omm
ent (
8).
AN
SAM
YCIN
SC
R
ifam
pin
5 µg
≤16
17-1
8≥
19≥
4≤
1 (1
0)R
x:R
ifam
pin
shou
ld n
ot b
e us
ed a
lone
for c
hem
othe
rapy
.LI
NC
OSA
MID
ESB
Clin
dam
ycin
2 µg
≤
1516
-18
≥19
≥1
≤0.
25S
ee c
omm
ent (
8).
STR
EPTO
GR
AM
INS
OQ
uinu
pris
tin-d
alfo
pris
tin
15 µ
g ≤
15
16-1
8≥
19≥
4 ≤
1O
XAZO
LID
INO
NES
CLi
nezo
lid30
µg
--
≥21
-≤
2S
ee c
omm
ent (
3).
January 2005 Vol. 25 No. 1
66
Tabl
e 2H
Stre
ptoc
occu
sspp
. O
ther
Tha
n S.
pne
umon
iae
M2-
Dis
k D
iffus
ion
©Clinical and Laboratory Standards Institute. All rights reserved.
Tabl
e 2H
. Zo
ne D
iam
eter
Inte
rpre
tive
Stan
dard
s an
d Eq
uiva
lent
Min
imal
Inhi
bito
ry C
once
ntra
tion
(MIC
) Bre
akpo
ints
forS
trep
toco
ccus
spp.
Oth
erTh
an S
trep
toco
ccus
pne
umon
iae
Test
ing
Con
ditio
ns
Med
ium
:M
uelle
r-H
into
n ag
ar w
ith 5
% s
heep
blo
odIn
ocul
um:
Dire
ct c
olon
y su
spen
sion
, equ
ival
ent t
o a
0.5
McF
arla
nd s
tand
ard
Incu
batio
n:35
°C
±2
degr
ees;
5%
CO
2;20
to 2
4 ho
urs
Min
imal
QC
Rec
omm
enda
tions
(See
Tab
le 3
Afo
r acc
epta
ble
QC
rang
es.)
Stre
ptoc
occu
s pn
eum
onia
eAT
CC
®49
619
Gen
eral
Com
men
ts
(1)
For
this
tabl
e, th
e be
ta-h
emol
ytic
gro
up in
clud
es th
e la
rge-
colo
ny-fo
rmin
g py
ogen
ic s
train
s of
stre
ptoc
occi
with
Gro
up A
(S. p
yoge
nes)
, C, o
r G
ant
igen
s an
dst
rain
s w
ith G
roup
B (S
. aga
lact
iae)
ant
igen
. Sm
all-c
olon
y-fo
rmin
g be
ta-h
emol
ytic
stra
ins
with
Gro
up A
, C, F
, or G
ant
igen
s (S
. ang
inos
us, p
revi
ousl
y te
rmed
“S.
mille
ri”)
are
cons
ider
ed p
art o
f the
viri
dans
gro
up, a
nd in
terp
retiv
e cr
iteria
for
the
virid
ans
grou
p sh
ould
be
used
. The
viri
dans
gro
up a
lso
incl
udes
S. m
itis,
S.
oral
is, S
. san
guis
, S. s
aliv
ariu
s, S
. int
erm
ediu
s, S
. con
stel
latu
s, S
. mut
ans,
and
S. b
ovis
.
(2)
Virid
ans
stre
ptoc
occi
isol
ated
from
nor
mal
ly s
teril
e bo
dy s
ites
(e.g
., ce
rebr
ospi
nal f
luid
, blo
od, b
one)
sho
uld
be te
sted
for
peni
cilli
n su
scep
tibili
ty u
sing
an
MIC
met
hod.
(3)
Sus
cept
ibili
ty te
stin
g of
pen
icill
ins
and
othe
r β-la
ctam
s ap
prov
ed b
y FD
Afo
r tre
atm
ent o
f Stre
ptoc
occu
s py
ogen
esor
Stre
ptoc
occu
s ag
alac
tiae
is n
ot n
eces
sary
for c
linic
al p
urpo
ses
and
need
not
be
done
rout
inel
y, s
ince
as
with
van
com
ycin
, res
ista
nt s
train
s ha
ve n
ot b
een
reco
gniz
ed.
Inte
rpre
tive
crite
ria a
re p
rovi
ded
for
phar
mac
eutic
al d
evel
opm
ent,
epid
emio
logy
, or
mon
itorin
g fo
r em
ergi
ng r
esis
tanc
e. A
ny s
train
fou
nd t
o be
non
susc
eptib
le s
houl
d be
ref
erre
d to
a r
efer
ence
labo
rato
ry fo
r con
firm
atio
n.
(4)
Inte
rpre
tive
crite
ria fo
r st
rept
ococ
ci a
re p
ropo
sed
base
d on
pop
ulat
ion
dist
ribut
ions
of v
ario
us s
peci
es, p
harm
acok
inet
ics
of th
e an
timic
robi
al a
gent
s, p
revi
ousl
ypu
blis
hed
liter
atur
e, a
nd th
e cl
inic
al e
xper
ienc
e of
cer
tain
mem
bers
of t
he s
ubco
mm
ittee
. Sys
tem
atic
ally
col
lect
ed c
linic
al d
ata
wer
e no
t ava
ilabl
e fo
r rev
iew
with
man
y of
the
com
poun
ds in
the
grou
p.
(5)
For
som
e or
gani
sm/a
ntim
icro
bial
age
nt c
ombi
natio
ns,
the
abse
nce
of r
esis
tant
stra
ins
prec
lude
s de
finin
g an
y re
sults
cat
egor
ies
othe
r th
an “
susc
eptib
le.”
For
stra
ins
yiel
ding
res
ults
sug
gest
ive
of a
“no
nsus
cept
ible
” ca
tego
ry,
orga
nism
ide
ntifi
catio
n an
d an
timic
robi
al s
usce
ptib
ility
tes
t re
sults
sho
uld
be c
onfir
med
.S
ubse
quen
tly, t
he is
olat
es s
houl
d be
sav
ed a
nd s
ubm
itted
to a
refe
renc
e la
bora
tory
that
will
con
firm
resu
lts u
sing
a C
LSI/N
CC
LS re
fere
nce
dilu
tion
met
hod.
NO
TE:
Info
rmat
ion
in b
oldf
ace
type
is c
onsi
dere
d te
ntat
ive
for o
ne y
ear.
For Use With M2-A8–Disk Diffusion M100-S15
67
Tabl
e 2H
Stre
ptoc
occu
sspp
. O
ther
Tha
n S.
pne
umon
iae
M2-
Dis
k D
iffus
ion
©Clinical and Laboratory Standards Institute. All rights reserved.
Tabl
e 2H
. (C
ontin
ued)
Test
/Rep
ort
Gro
up
Ant
imic
robi
al
Age
nt
Dis
k C
onte
nt
Zone
Dia
met
er,
Nea
rest
Who
le m
m
Equi
vale
nt M
ICB
reak
poin
ts (µµ
g/m
L)
Com
men
tsR
I
S R
S
PEN
ICIL
LIN
S(6
) A
stre
ptoc
occa
l iso
late
that
is s
usce
ptib
le to
pen
icill
inca
n be
con
side
red
susc
eptib
le t
o am
pici
llin,
am
oxic
illin
,am
oxic
illin
-cla
vula
nic
acid
, am
pici
llin-
sulb
acta
m, c
efac
lor,
cefa
zolin
, ce
fdin
ir,
cefe
pim
e,
cefp
rozi
l, ce
fota
xim
e,ce
ftibu
ten
(Gro
up A
stre
ptoc
occi
on
ly),
ceftr
iaxo
ne,
cefu
roxi
me,
ce
fpod
oxim
e,
cefti
zoxi
me,
ce
phal
othi
n,ce
phap
irin,
ce
phra
dine
, im
ipen
em,
lora
carb
ef,
and
mer
open
em f
or a
ppro
ved
indi
catio
ns,
and
need
not
be
test
ed a
gain
st th
ose
agen
ts.
A AP
enic
illin
(bet
a-he
mol
ytic
gro
up) o
ram
pici
llin
(bet
a-he
mol
ytic
gro
up)
10 u
nits
10 µ
g- -
- - ≥
24≥
24- -
≤0.
12≤
0.25
(7) B
reak
poin
ts a
re fo
r bet
a-he
mol
ytic
stre
ptoc
occi
onl
y.P
enic
illin
, am
pici
llin,
and
oxa
cilli
n di
sk d
iffus
ion
test
ing
isno
t rel
iabl
e w
ith v
irida
ns s
trept
ococ
ci.
See
com
men
t (5)
.C
EPH
EMS
(PA
REN
TER
AL)
(In
clud
ing
ceph
alos
porin
s I,
II, II
I, an
d IV
. Ple
ase
refe
r to
Glo
ssar
y I.)
S
ee c
omm
ent (
6).
C C C C C C
Cef
epim
e (b
eta-
hem
olyt
ic g
roup
)or ce
fota
xim
e (b
eta-
hem
olyt
ic g
roup
)or ce
ftria
xone
(bet
a-he
mol
ytic
gro
up)
Cef
epim
e (v
irida
ns g
roup
) or
cefo
taxi
me
(viri
dans
gro
up) o
rce
ftria
xone
(viri
dans
gro
up)
30 µ
g
30 µ
g
30 µ
g
30 µ
g30
µg
30 µ
g
- - -
≤21
≤25
≤24
- - -
22-2
326
-27
25-2
6
≥24
≥24
≥24
≥24
≥28
≥27
- - - ≥4
≥4
≥4
≤0.
5
≤0.
5
≤0.
5
≤1
≤1
≤1
See
com
men
t (5)
.
GLY
CO
PEPT
IDES
BVa
ncom
ycin
30 µ
g-
-≥
17-
≤1
See
com
men
t (5)
.LI
POPE
PTID
ESC
Dap
tom
ycin
30 µµ
g-
-≥≥
16-
≤≤1
See
com
men
t (5)
.M
AC
RO
LID
ES(8
) Su
scep
tibilit
y an
d re
sist
ance
to a
zith
rom
ycin
, cla
rithr
o-m
ycin
, an
d di
rithr
omyc
in
can
be
pred
icte
d by
te
stin
ger
ythr
omyc
in.
(9)
Not
rout
inel
y re
porte
d on
isol
ates
from
the
urin
ary
tract
.A
Ery
thro
myc
in15
µg
≤15
16-2
0≥
21≥
1≤
0.25
(10)
R
x:
Rec
omm
enda
tions
fo
r in
trap
artu
mpr
ophy
laxi
s fo
r G
roup
B s
trep
toco
cci a
re p
enic
illin
or
ampi
cilli
n.
Whi
le
cefa
zolin
is
re
com
men
ded
for
peni
cilli
n-al
lerg
ic w
omen
at
low
ris
k fo
r an
aphy
laxi
s,th
ose
at
high
ri
sk
for
anap
hyla
xis
may
re
ceiv
ecl
inda
myc
in o
r er
ythr
omyc
in.
Gro
up B
str
epto
cocc
iar
e su
scep
tible
to a
mpi
cilli
n, p
enic
illin
, and
cef
azol
in,
but
may
be
re
sist
ant
to
clin
dam
ycin
an
d/or
eryt
hrom
ycin
. W
hen
a G
roup
B
st
rept
ococ
cus
isis
olat
ed fr
om a
pre
gnan
t wom
an w
ith s
ever
e pe
nici
llin
alle
rgy
(hig
h ris
k fo
r an
aphy
laxi
s),
clin
dam
ycin
and
eryt
hrom
ycin
sho
uld
be te
sted
and
rep
orte
d.
January 2005 Vol. 25 No. 1
68
Tabl
e 2H
Stre
ptoc
occu
sspp
. O
ther
Tha
n S.
pne
umon
iae
M2-
Dis
k D
iffus
ion
©Clinical and Laboratory Standards Institute. All rights reserved.
Tabl
e 2H
. (C
ontin
ued)
Test
/Rep
ort
Gro
up
Ant
imic
robi
al
Age
nt
Dis
k C
onte
nt
Zone
Dia
met
er,
Nea
rest
Who
le m
m
Equi
vale
nt M
ICB
reak
poin
ts (µµ
g/m
L)
Com
men
tsR
I
S R
S
MA
CR
OLI
DES
(Con
tinue
d)O
A
zith
rom
ycin
15 µ
g≤
1314
-17
≥18
≥2
≤0.
5O
C
larit
hrom
ycin
15 µ
g≤
1617
-20
≥21
≥1
≤0.
25O
D
irith
rom
ycin
15 µ
g≤
1314
-17
≥18
≥2
≤0.
5TE
TRA
CYC
LIN
ESO
Te
tracy
clin
e 30
µg
≤18
19-2
2≥
23≥
8≤
2(1
1)
Org
anis
ms
that
are
sus
cept
ible
to
tetra
cycl
ine
are
also
cons
ider
ed s
usce
ptib
le to
dox
ycyc
line
and
min
ocyc
line.
FLU
OR
OQ
UIN
OLO
NES
CLe
voflo
xaci
n5
µg≤
1314
-16
≥17
≥8
≤2
(12)
B
reak
poin
ts
are
for
repo
rting
ag
ains
t be
ta-h
emol
ytic
stre
ptoc
occi
onl
y.C
Oflo
xaci
n5
µg≤
1213
-15
≥16
≥8
≤2
See
com
men
t (12
).O
Gat
iflox
acin
5 µg
≤17
18
-20
≥21
≥4
≤1
See
com
men
t (12
).O
Gre
paflo
xaci
n5
µg≤
1516
-18
≥19
≥2
≤0.
5O
Trov
aflo
xaci
n10
µg
≤15
16-1
8≥
19
≥4
≤1
PHEN
ICO
LSB
Chl
oram
phen
icol
30 µ
g≤
1718
-20
≥21
≥16
≤4
See
com
men
t (9)
.LI
NC
OSA
MID
ESB
Clin
dam
ycin
2 µg
≤15
16-1
8≥
19≥
1≤
0.25
See
com
men
ts (6
)and
(10)
.(1
3)
Mac
rolid
e-re
sist
ant
isol
ates
of
be
ta-h
emol
ytic
stre
ptoc
occi
may
hav
e co
nstit
utiv
e or
indu
cibl
e re
sist
ance
to c
linda
myc
in [m
ethy
latio
n of
the
23S
rRN
Aen
code
d by
an
erm
gene
als
o re
ferr
ed to
as
MLS
B(m
acro
lide,
linc
osam
ide,
and
type
B s
trep
togr
amin
) re
sist
ance
] or
may
be
resi
stan
ton
ly t
o m
acro
lides
(ef
flux
mec
hani
sm e
ncod
ed b
y a
mef
gene
). In
duci
ble
clin
dam
ycin
res
ista
nce
can
be d
etec
ted
usin
g a
disk
ap
prox
imat
ion
test
by
pl
acin
g a
2-µg
clin
dam
ycin
di
sk
12
mm
fr
om
the
edge
of
a
15-µ
ger
ythr
omyc
in d
isk
as p
art
of t
he n
orm
al d
isk
diffu
sion
proc
edur
e. F
ollo
win
g in
cuba
tion,
org
anis
ms
that
do
not
show
flat
teni
ng o
f the
clin
dam
ycin
zon
e sh
ould
be
repo
rted
as
clin
dam
ycin
su
scep
tible
. O
rgan
ism
s th
at
show
flatt
enin
g of
th
e cl
inda
myc
in
zone
ad
jace
nt
to
the
eryt
hrom
ycin
di
sk
(ref
erre
d to
as
a
“D”
zone
) ha
vein
duci
ble
clin
dam
ycin
res
ista
nce.
Suc
h is
olat
es s
houl
d be
repo
rted
as
“clin
dam
ycin
res
ista
nt.”
Aco
mm
ent t
hat “
This
isol
ate
is p
resu
med
to
be r
esis
tant
bas
ed o
n de
tect
ion
ofin
duci
ble
clin
dam
ycin
res
ista
nce.
Clin
dam
ycin
may
stil
l be
effe
ctiv
e in
som
e pa
tient
s.”
may
be
incl
uded
.ST
REP
TOG
RA
MIN
SC
Qui
nupr
istin
-dal
fopr
istin
15 µ
g ≤
1516
-18
≥19
≥4
≤1
(14)
B
reak
poin
ts a
re f
or r
epor
ting
agai
nst
Stre
ptoc
occu
spy
ogen
eson
ly.O
XAZO
LID
INO
NES
CLi
nezo
lid30
µg
--
≥21
-≤
2S
ee c
omm
ent (
5).
For Use With M2-A8–Disk Diffusion M100-S15
©Clinical and Laboratory Standards Institute. All rights reserved.69
Test
/Rep
ort
Gro
up
Ant
imic
robi
al
Age
nt
Dis
k C
onte
nt
Zone
Dia
met
er,
Nea
rest
Who
le m
m
Equi
vale
nt M
ICB
reak
poin
ts (µµ
g/m
L)
Com
men
tsR
I
S R
S
PEN
ICIL
LIN
SA
Am
pici
llin
10 µ
g≤
1314
-16
≥17
≥32
≤8
(2)
Cla
ss
repr
esen
tativ
e fo
r am
pici
llin
and
amox
icill
in.
TETR
AC
YCLI
NES
CTe
tracy
clin
e30
µg
≤14
15-1
8≥
19≥
16≤
4(3
) Te
tracy
clin
e re
sults
can
be
used
to p
redi
ctth
e lik
ely
susc
eptib
ility
of i
sola
tes
todo
xycy
clin
e; d
o no
t use
dis
k te
st fo
rdo
xycy
clin
e, a
s th
ere
is p
oor c
orre
latio
n w
ithM
IC re
sults
.FO
LATE
PAT
HW
AYIN
HIB
ITO
RS
BTr
imet
hopr
im-s
ulfa
met
hoxa
zole
1.25
/23.
75 µ
g≤
1011
-15
≥16
≥8/
152
≤2/
38C
Sul
fona
mid
es25
0 µg
or
300
µg≤
1213
-16
≥17
≥35
0≤
100
(4)
The
sulfi
soxa
zole
dis
k ca
n be
use
d to
repr
esen
t any
of t
he c
urre
ntly
ava
ilabl
esu
lfona
mid
e pr
epar
atio
ns.
PHEN
ICO
LSC
Chl
oram
phen
icol
30 µ
g≤
1213
-17
≥18
≥32
≤8
(5)
Use
with
cau
tion
as d
isk
diffu
sion
test
may
mis
clas
sify
man
y or
gani
sms
(hig
her m
inor
err
orra
te).
Gen
eral
Com
men
ts
(1)
The
resu
lts o
f di
sk d
iffus
ion
test
s fo
r am
pici
llin,
tet
racy
clin
e, t
rimet
hopr
im-s
ulfa
met
hoxa
zole
, an
d su
lfona
mid
es (
i.e.,
perc
enta
ge o
f su
scep
tible
,in
term
edia
te, a
nd re
sist
ant)
corr
elat
e w
ell w
ith re
sults
det
erm
ined
by
brot
h m
icro
dilu
tion.
Dis
k di
ffusi
on te
sts
shou
ld n
ot b
e us
ed fo
r ery
thro
myc
in, b
ecau
seth
ere
is a
poo
r cor
rela
tion
with
MIC
resu
lts.
NO
TE:
Info
rmat
ion
in b
oldf
ace
type
is c
onsi
dere
d te
ntat
ive
for o
ne y
ear.
Min
imal
QC
Rec
omm
enda
tions
(See
Tab
le 3
for a
ccep
tabl
e Q
C ra
nges
.)
Esch
eric
hia
coli
ATC
C®
2592
2
Test
ing
Con
ditio
ns
Med
ium
:M
uelle
r-H
into
n ag
arIn
ocul
um:
Gro
wth
met
hod
or d
irect
col
ony
susp
ensi
on,
equi
vale
nt to
a 0
.5 M
cFar
land
sta
ndar
d.In
cuba
tion:
35 °
C ±
2 de
gree
s; a
mbi
ent a
ir; 1
6 to
18
hour
s
Tabl
e 2I
. Zo
ne D
iam
eter
Inte
rpre
tive
Stan
dard
s an
d Eq
uiva
lent
Min
imal
Inhi
bito
ry C
once
ntra
tion
(MIC
) Bre
akpo
ints
for V
ibrio
cho
lera
e
Tabl
e 2I
Vibr
io c
hole
rae
M2-
Dis
k D
iffus
ion
January 2005 Vol. 25 No. 1
©Clinical and Laboratory Standards Institute. All rights reserved.70
Tabl
e 3
Non
fast
idio
us Q
ualit
y C
ontro
lM
2-D
isk
Diff
usio
n
Table 3. Acceptable Limits for Quality Control Strains Used to Monitor Accuracy of Disk DiffusionTesting of Nonfastidious Organisms (Using Mueller-Hinton Medium Without Blood or OtherSupplements)
AntimicrobialAgent
Disk ContentEscherichia
coliATCC® 25922a
Staphylococcusaureus
ATCC® 25923
Pseudomonasaeruginosa
ATCC® 27853
Escherichiacoli
ATCC® 35218b
AmikacinAmoxicillin-clavulanic acidAmpicillinAmpicillin-sulbactamAzithromycinAzlocillinAztreonamCarbenicillinCefaclorCefamandoleCefazolinCefdinirCefditorenCefepimeCefetametCefiximeCefmetazoleCefonicidCefoperazoneCefotaximeCefotetanCefoxitin Cefpodoxime CefprozilCeftazidimeCeftibutenCeftizoximeCeftriaxoneCefuroximeCephalothinChloramphenicolCinoxacinCiprofloxacinClarithromycinClinafloxacinClindamycinc
ColistinDaptomycind
DirithromycinDoripenemDoxycyclineEnoxacinErtapenemErythromycinc
FleroxacinFosfomycine
GarenoxacinGatifloxacinGemifloxacinGentamicinfGrepafloxacinImipenemKanamycinLevofloxacinLinezolidLomefloxacinLoracarbefMecillinam
30 µg 20/10 µg
10 µg10/10 µg
15 µg75 µg30 µg
100 µg30 µg30 µg30 µg5 µg5 µg30 µg10 µg5 µg30 µg30 µg75 µg30 µg30 µg30 µg10 µg30 µg30 µg30 µg30 µg30 µg30 µg30 µg30 µg
100 µg5 µg15 µg5 µg2 µg
10 µµg30 µg15 µg10 µµg30 µg10 µg10 µg15 µg5 µg
200 µg5 µg5 µg5 µg10 µg5 µg10 µg30 µg5 µg30 µg10 µg30 µg10 µg
19-26 18-2416-2219-24
--
28-3623-2923-2726-3221-2724-2822-2831-3724-2923-2726-3225-2928-3429-3528-3423-2923-2821-2725-3227-3530-3629-3520-2615-2121-2726-3230-40
-31-40
-11-17
--
28-3518-2428-3629-36
-28-3422-3028-3530-3729-3619-2628-3626-3217-2529-37
-27-3323-2924-30
20-26 28-3627-3529-3721-26
---
27-3126-3429-3525-3220-2823-29
--
25-3422-2824-3325-3117-2323-2919-2527-3316-20
-27-3522-2827-3529-3719-26
-22-3026-3228-3724-30
-18-2318-2633-4223-2922-2824-3122-3021-2725-3330-3627-3327-3319-2726-31
-19-2625-3025-3223-2923-31
-
18-26----
24-3023-2918-24
-----
24-30----
23-2918-22
----
22-29-
12-1717-23
----
25-33-
27-35-
11-17--
29-35-
22-2813-21
-12-20
-19-2520-2819-2516-2120-2720-28
-19-26
-22-28
--
-17-22
613-19
---------------------------------------
---------------
For Use With M2-A8–Disk Diffusion M100-S15
71©Clinical and Laboratory Standards Institute. All rights reserved.
NOTE: Information in boldface type is considered tentative for one year.
Footnotes
a. ATCC is a registered trademark of the American Type Culture Collection.b. Careful organism maintenance is required; refer to M2, Section 10.3.c. When disk approximation tests are performed with erythromycin and clindamycin, S. aureus ATCC® BAA-
977 (containing inducible ermA-mediated resistance) and S. aureus ATCC® BAA-976 (containing msrA-mediated macrolide-only efflux) are recommended for quality assessment purposes (e.g., training,competency assessment, or test evaluation). S. aureus ATCC® BAA-977 should demonstrate inducibleclindamycin resistance (i.e., a positive D-zone test), while S. aureus ATCC® BAA-976 should notdemonstrate inducible clindamycin resistance. S. aureus ATCC® 25923 should be used for routine qualitycontrol (e.g., weekly or daily) of erythromycin and clindamycin disks using standard Mueller-Hinton agar.
d. Some lots of Mueller-Hinton agar are deficient in calcium and give small zones.e. The 200-µg fosfomycin disk contains 50 µg of glucose-6-phosphate.f. For control limits of gentamicin 120-µg and streptomycin 300-µg disks, use Enterococcus faecalis ATCC® 29212
(gentamicin: 16 to 23 mm; streptomycin: 14 to 20 mm).g. These agents can be affected by excess levels of thymidine and thymine. See M2, Section 4.1.4 for guidance should
a problem with quality control occur.
Table 3. (Continued)
AntimicrobialAgent Disk Content
Escherichiacoli
ATCC® 25922a
Staphylococcusaureus
ATCC® 25923
Pseudomonasaeruginosa
ATCC® 27853
Escherichiacoli
ATCC® 35218b
MeropenemMethicillinMezlocillinMinocyclineMoxalactamMoxifloxacinNafcillinNalidixic acidNetilmicinNitrofurantoinNorfloxacinOfloxacinOxacillinPenicillinPiperacillinPiperacillin-tazobactamPolymyxin BQuinupristin-dalfopristinRifampinSparfloxacinStreptomycinf
Sulfisoxazoleg
TeicoplaninTelavancinTelithromycinTetracyclineTicarcillinTicarcillin-clavulanic acidTigecyclineTobramycinTrimethoprimg
Trimethoprim-sulfamethoxazoleg
TrospectomycinTrovafloxacinVancomycin
10 µg5 µg75 µg30 µg30 µg5 µg1 µg30 µg30 µg
300 µg10 µg5 µg1 µg
10 units100 µg
100/10 µg300 units
15 µg5 µg5 µg10 µg
250 µg or 300 µg30 µg30 µµg15 µg30 µg75 µg
75/10 µg15 µµg10 µg5 µg
1.25/23.75 µg30 µg10 µg30 µg
28-34-
23-2919-2528-3528-35
-22-2822-3020-2528-3529-33
--
24-3024-3013-19
-8-10
30-3812-2015-23
---
18-2524-3024-3020-2718-2621-2823-2910-1629-36
-
29-3717-22
-25-3018-2428-3516-22
-22-3118-2217-2824-2818-2426-37
-27-36
-21-2826-3427-3314-2224-3415-2116-2024-3024-30
-29-3720-2519-2919-2624-3215-2029-3517-21
27-33-
19-25-
17-2517-25
--
17-23-
22-2917-21
--
25-3325-3314-18
--
21-29------
21-2720-289-13
19-25---
21-27-
--------------
12-1824-30
----------6
21-25- ------
Tabl
e 3
Non
fast
idio
us Q
ualit
y C
ontro
lM
2-D
isk
Diff
usio
n
Tabl
e 3A
Fast
idio
us Q
ualit
y C
ontro
lM
2-D
isk
Diff
usio
nJanuary 2005 Vol. 25 No. 1
72 ©Clinical and Laboratory Standards Institute. All rights reserved.
Table 3A. Acceptable Limits for Quality Control Strains Used to Monitor Accuracy of DiskDiffusion Testing of Fastidious Organisms
AntimicrobialAgent Disk Content
Haemophilusinfluenzae ATCC®
49247a
Haemophilusinfluenzae
ATCC® 49766
Neisseria gonorrhoeae ATCC® 49226
Streptococcuspneumoniae
ATCC® 49619b
Amoxicillin-clavulanic acidc
AmpicillinAmpicillin-sulbactamAzithromycinAztreonamCefaclorCefdinirCefditorenCefepimeCefetametCefiximeCefmetazoleCefonicidCefotaximeCefotetanCefoxitinCefpodoximeCefprozilCeftazidimeCeftibutenCeftizoximeCeftriaxoneCefuroximeCephalothinChloramphenicolCiprofloxacinClarithromycinClinafloxacinClindamycinDaptomycind
DirithromycinDoripenemEnoxacinErtapenemErythromycinFleroxacinGarenoxacinGatifloxacin Gemifloxacin Grepafloxacin ImipenemLevofloxacinLinezolidLomefloxacinLoracarbefMeropenemMoxifloxacinNitrofurantoinNorfloxacinOfloxacinOxacillinPenicillinPiperacillin-tazobactamQuinupristin-dalfopristinRifampin
20/10 µg10 µg
10/10 µg15 µg30 µg30 µg5 µg5 µg
30 µg10 µg5 µg
30 µg30 µg30 µg30 µg30 µg10 µg30 µg30 µg30 µg30 µg30 µg30 µg30 µg30 µg5 µg
15 µg5 µg2 µg
30 µg15 µg10 µµg10 µg10 µg15 µg5 µg5 µg5 µg5 µg5 µg
10 µg5 µg 30 µg10 µg30 µg10 µg5 µg
300 µg10 µg5 µg1 µg
10 units100/10 µg
15 µg5 µg
15-2313-2114-2213-2130-38
--
25-3425-3123-2825-3316-21
-31-39
--
25-31-
27-3529-3629-3931-39
--
31-4034-4211-1734-43
---
21-31-
20-28-
30-3833-4133-4130-3732-3921-2932-40
- 33-41
-20-2831-39
--
31-40--
33-3815-2122-30
-----
25-3124-31
-----
30-38----
20-27----
28-36----------
27-33----------
26-32----------
------
40-49-
37-4635-4337-4531-36
-38-4830-3633-4135-43
-35-43
-42-5139-5133-41
--
48-58------
43-51--
43-51-
45-56 -
44-52 ---
45-54-----
43-51-
26-34---
-30-36
-19-25
-24-3226-3127-3528-35
-16-23
--
31-39--
28-3425-32
--
28-3430-35
-26-3223-27
-25-3127-3419-2519-2618-2530-38
-28-3525-30
-26-3324-31 28-34 21-28
-20-25 25-34
-22-2828-3525-3123-2915-2116-21≤ 12e
24-30-
19-2425-30
©Clinical and Laboratory Standards Institute. All rights reserved.
For Use With M2-A8–Disk Diffusion M100-S15
73
Table 3A. (Continued)
Organism Haemophilus influenzae Neisseria gonorrhoeae Streptococcus pneumoniae
Medium Haemophilus Test Medium GC agar base and 1% definedgrowth supplement. The use ofa cysteine-free growthsupplement is not required fordisk diffusion testing.
MHA supplemented with 5%defibrinated sheep blood
Inoculum Direct colony suspension Direct colony suspension Direct colony suspension
Incubation Characteristics 5% CO2; 16 to 18 hours; 35 °C 5% CO2; 20 to 24 hours; 35 °C 5% CO2; 20 to 24 hours; 35 °C
Disk Diffusion Testing Conditions for Clinical Isolates and Performance of Quality Control
NOTE: Information in boldface is considered tentative for one year.
Footnotes
a. ATCC is a registered trademark of American Type Culture Collection.
b. Despite the lack of reliable disk diffusion interpretive criteria for S. pneumoniae with certain β-lactams, Streptococcuspneumoniae ATCC® 49619 is the strain designated for quality control of all disk diffusion tests with all Streptococcus spp.
c. When testing Haemophilus on HTM, the acceptable limits for QC strain E. coli ATCC® 35218 are 17 to 22 mm for amoxicillin-clavulanic acid.
d. Some lots of Mueller-Hinton agar are deficient in calcium and give small zones.
e. Deterioration in oxacillin disk content is best assessed with QC organism Staphylococcus aureus ATCC® 25923, with anacceptable zone diameter of 18 to 24 mm.
AntimicrobialAgent Disk Content
Haemophilusinfluenzae
ATCC® 49247a
Haemophilusinfluenzae
ATCC® 49766
Neisseria gonorrhoeae ATCC® 49226
Streptococcuspneumoniae
ATCC® 49619b
SparfloxacinSpectinomycinTelavancinTelithromycinTetracyclineTigecyclineTrimethoprim-sulfamethoxazoleTrospectomycinTrovafloxacinVancomycin
5 µg100 µg30 µµg15 µg30 µg15 µµg
1.25/23.75 µg30 µg10 µg30 µg
32-40--
17-2314-2223-3124-3222-2932-39
-
----------
43-5123-29
--
30-4230-40
-28-3542-55
-
21-27-
17-2427-3327-3123-2920-28
-25-3220-27
Tabl
e 3A
Fast
idio
us Q
ualit
y C
ontro
lM
2-D
isk
Diff
usio
n
74 ©Clinical and Laboratory Standards Institute. All rights reserved.
January 2005 Vol. 25 No. 1
Tabl
e 3B
QC
Tes
ting
Freq
uenc
yM
2-D
isk
Diff
usio
n
NOTE 1: Addition of any NEW antimicrobial agent requires 20 or 30 consecutive days of satisfactory testing (see M2-A8,Section 10.5) prior to use of this guide.
NOTE 2: QC can be performed prior to or concurrent with testing patient isolates. Patient results can be reported for that day ifquality control results are within the acceptable limits.
NOTE 3: Manufacturers of commercial or in-house prepared tests should follow their own internal procedures and applicableregulations.
NOTE 4: For troubleshooting out-of-range results, refer to M2-A8, Section 10.6.
NOTE 5: Broth, saline, and/or water used to prepare an inoculum does not require routine quality control.
FOOTNOTE
a. Does not eliminate the need for routine weekly or daily QC testing.
Number of Days of Consecutive QCTesting Requireda
Test Modification 1 5 20 or 30 CommentsDisksUse new shipment or lot number XUse new manufacturer XMedia (prepared agar plates)Use new shipment or lot number XUse new manufacturer XInoculum PreparationConvert inoculum preparation/standardization to use of a devicethat has its own QC protocol.
X Example:Convert from visual adjustmentof turbidity to use of aphotometric device for which aquality control procedure isprovided.
Convert inoculum preparation/standardization to a method that isdependent on user technique.
X Example:Convert from visual adjustmentof turbidity to another methodthat is not based on aphotometric device.
Measuring ZonesChange method of measuringzones.
X Example:Convert from manual zonemeasurements to automatedzone reader.
In addition, perform in-housevalidation studies.
Instrument/Software (e.g., automated zone reader)Software update that affects ASTresults
X Monitoring all drugs, not justthose implicated in softwaremodification
Repair of instrument that affectsAST results
X Depending on extent of repair(e.g., critical component such asthe photographic device),additional testing may beappropriate (e.g., five days).
Table 3B. Reference Guide to Quality Control Testing Frequency
This table summarizes the suggested frequency of testing CLSI/NCCLS-recommended ATCC qualitycontrol strains to be performed by the user of antimicrobial susceptibility tests (AST). It applies only toantimicrobial agents for which 20 or 30 consecutive test days of quality control testing producedsatisfactory results.
For Use With M2-A8–Disk Diffusion M100-S15
75©Clinical and Laboratory Standards Institute. All rights reserved.
This page is intentionally left blank.
January 2005 Vol. 25 No. 1
76
Tabl
e 4
Sugg
este
d Te
st Re
sult
Verif
icat
ion
and
Org
anism
Iden
tific
atio
nM
2-D
isk
Diff
usio
n
©Clinical and Laboratory Standards Institute. All rights reserved.
a When results listed in this category are observed on individual patient isolates, they should be verified by one or moreof the following:
1. Ensuring the unusual results are not due to transcription errors, contamination, or use of a defective panel,plate, or card.
2. Checking previous reports on the patient to determine if the isolate was encountered and verified earlier.3. Confirming the identification of the isolate.4. Repeating the susceptibility test to confirm results. Sometimes it is helpful to use an alternative test method
for the repeat test. 5. For isolates that show results other than susceptible for those antimicrobial agents for which only susceptible
interpretive criteria are provided in Tables 2A to 2I (listed with an “NS” above) and for staphylococci withvancomycin-intermediate or vancomycin-resistant results: 1) confirm the organism identification; 2) confirmthe antimicrobial susceptibility test results; 3) save the isolate; and 4) submit the isolate to a referencelaboratory that will test it by a CLSI/NCCLS reference dilution method.
b When results listed in this category are observed on individual patient isolates, the verification steps as outlined forCategory I should be considered if the resistance is uncommon in a given institution.
c For these antimicrobial agent/organism combinations, resistance has not been documented to date.d
When submitting reports to a public health laboratory, include antimicrobial susceptibility results forSalmonella spp. that are intermediate or resistant to 3rd-generation cephalosporins and/or intermediate orresistant to fluoroquinolone or resistant to nalidixic acid.
Table 4. Suggestions for Verification of Antimicrobial Susceptibility Test Results and Confirmationof Organism Identification
This table reflects the drugs listed for testing against the respective organisms in Tables 2A to 2I in M100and gives some examples to consider for verification protocols at a given institution. The list includesphenotypes that: 1) have never been documented; 2) are uncommon; and/or 3) represent results thatcould easily occur from technical errors and may have significant clinical consequences.
Organism or GroupCategory Ia
Phenotypes that have not beenreported, are uncommon, and/or
result from technical errors
Category IIb
Phenotypes that may be uncommon at agiven institution and/or result from
technical errors Gram-negative organismsEnterobacteriaceae (any) carbapenem - I or R amikacin - R
fluoroquinolone - R
Citrobacter freundii Enterobacter spp. Serratia marcescens
ampicillin, cefazolin, or cephalothin- S
Escherichia coli ESBL confirmed positiveKlebsiella spp. ampicillin - S ESBL confirmed positiveProteus vulgaris Providencia spp.
ampicillin - S
Salmonella spp. 3rd-generation cephalosporin - I or Rd
fluoroquinolone - I or R; or nalidixicacid - Rd
Pseudomonas aeruginosa concurrent gentamicin and tobramycinand amikacin - R
Stenotrophomonas maltophilia
carbapenem - S trimethoprim-sulfamethoxazole - R
Haemophilus influenzae aztreonam - NS carbapenem - NS3rd-generation cephalosporinc - NSfluoroquinolone - NS
ampicillin - R and β-lactamase-negativeamoxicillin-clavulanic acid - R
Neisseria gonorrhoeae 3rd-generation cephalosporin - R fluoroquinolone - RAny organism Resistant to all agents routinely
tested
For Use With M2-A8–Disk Diffusion M100-S15
77
Tabl
e 4
Sugg
este
d Te
st Re
sult
Verif
icat
ion
and
Org
anism
Iden
tific
atio
nM
2-D
isk
Diff
usio
n
©Clinical and Laboratory Standards Institute. All rights reserved.
Organism or Group
Category Ia
Phenotypes that have not beenreported, are uncommon, and/or
result from technical errors
Category IIb
Phenotypes that may be uncommonat a given institution and/or result
from technical errors
Gram-positive organismsEnterococcus spp. daptomycin - NS vancomycin - REnterococcus faecalis ampicillin or penicillin - R
daptomycin - NSquinupristin-dalfopristin - Slinezolid - R
high-level aminoglycoside - R(particularly if isolate from sterile bodysite)
Enterococcus faecium daptomycin - NSlinezolid - R
high-level aminoglycoside - R(particularly if isolate from sterile bodysite)
quinupristin-dalfopristin - R
Staphylococcus aureus daptomycin - NSlinezolid - NS quinupristin-dalfopristin - I or Rvancomycin - I or R
oxacillin - R
Staphylococcus,coagulase-negative
daptomycin - NSlinezolid - NS vancomycin - I or R
Streptococcuspneumoniae
fluoroquinolone - Rlinezolidc - NSvancomycinc - NS
penicillin - R3rd-generation cephalosporin - R
Streptococcus, beta group
ampicillin or penicillinc - NS3rd-generation cephalosporin - NSdaptomycin - NSlinezolid - NSvancomycinc - NS
Streptococcus, viridansgroup
daptomycin - NSlinezolid - NSvancomycin - NS
penicillin - I or R
Any organism Resistant to all agents routinely tested
a When results listed in this category are observed on individual patient isolates, they should be verified by one or moreof the following:
1. Ensuring the unusual results are not due to transcription errors, contamination, or use of a defective panel,plate, or card.
2. Checking previous reports on the patient to determine if the isolate was encountered and verified earlier.3. Confirming the identification of the isolate.4. Repeating the susceptibility test to confirm results. Sometimes it is helpful to use an alternative test method
for the repeat test. 5. For isolates that show results other than susceptible for those antimicrobial agents for which only susceptible
interpretive criteria are provided in Tables 2A to 2I (listed with an “NS” above) and for staphylococci withvancomycin-intermediate or vancomycin-resistant results: 1) confirm the organism identification; 2) confirmthe antimicrobial susceptibility test results; 3) save the isolate; and 4) submit the isolate to a referencelaboratory that will test it by a CLSI/NCCLS reference dilution method.
b When results listed in this category are observed on individual patient isolates, the verification steps as outlined forCategory I should be considered if the resistance is uncommon in a given institution.
c For these antimicrobial agent/organism combinations, resistance has not been documented to date.
Table 4. (Continued)
January 2005 Vol. 25 No. 1
78 ©Clinical and Laboratory Standards Institute. All rights reserved.
Glossary I (Part 1). ββ-lactams: Class and Subclass Designation and Generic NameAntimicrobial Class Antimicrobial Subclass Agents Included; Generic Namespenicillins penicillina penicillin
aminopenicillina amoxicillin
ampicillin
ureidopencillina azlocillinmezlocillinpiperacillin
carboxypenicillina carbenicillinticarcillin
penicillinase-stable
penicillinsb
cloxacillindicloxacillinmethicillinnafcillinoxacillin
amidinopenicillin mecillinamβ-lactam/β-lactamaseinhibitor combinations
amoxicillin-clavulanic acidampicillin-sulbactampiperacillin-tazobactamticarcillin-clavulanic acid
cephems (parenteral) cephalosporin Ic,e cefazolin
cephalothincephapirincephradine
cephalosporin IIc,e cefamandole
cefonicidcefuroxime (sodium)
cephalosporin IIIc,e cefoperazone
cefotaximeceftazidimeceftizoximeceftriaxone
cephalosporin IVc,e cefepime cephamycind cefmetazole
cefotetancefoxitin
oxacephem moxalactamcephems (oral) cephalosporine cefaclor
cefadroxilcefdinircefditorencefetametcefiximecefpodoximecefprozilceftibutencefuroxime (axetil)cephalexincephradine
carbacephem loracarbefmonobactams aztreonamcarbapenems doripenem
ertapenemimipenemmeropenem
a Penicillinase-labile; hydrolyzed by staphylococcal penicillinase.
b Not hydrolyzed by staphylococcal penicillinase.c Cephalosporin I, II, III, and IV are sometimes referred to as 1st-, 2nd-, 3rd-, and 4th-generation cephalosporins, respectively.
Cephalosporin III and IV are also referred to as “extended-spectrum cephalosporins.” This does not imply activity against ESBL-producing gram-negativebacteria.
d Although often referred to as a 2nd-generation cephalosporin, cephamycins are not included with the other cephalosporins with regard to reporting of ESBL-producing strains.
e For all confirmed ESBL-producing strains, the test interpretation should be reported as resistant for this antimicrobial class or subclass.
Glo
ssar
y I
For Use With M2-A8–Disk Diffusion M100-S15
©Clinical and Laboratory Standards Institute. All rights reserved. 79
Glossary I (Part 2). Non-ββ-lactams: Class and Subclass Designation and Generic Name
Antimicrobial Class Antimicrobial Subclass Agents Included; Generic Namesaminocyclitols spectinomycin
trospectinomycinaminoglycosides amikacin
gentamicinkanamycinnetilmicinstreptomycintobramycin
ansamycins rifampinquinolones quinolone cinoxacin
garenoxacinnalidixic acid
fluoroquinolone ciprofloxacinclinafloxacinenoxacinfleroxacingatifloxacingemifloxacingrepafloxacinlevofloxacinlomefloxacinmoxifloxacinnorfloxacinofloxacinsparfloxacintrovafloxacin
folate pathway inhibitors sulfonamidestrimethoprimtrimethoprim-sulfamethoxazole
fosfomycins fosfomycinketolides telithromycinlincosamides clindamycinlipopeptides daptomycin
polymyxins colistin polymyxin B
macrolides azithromycinclarithromycindirithromycinerythromycin
nitrofurans nitrofurantoinnitroimidazoles metronidazoleoxazolidinones linezolidglycopeptides glycopeptide oritavancin
vancomycinlipoglycopeptide dalbavancin
teicoplanintelavancin
phenicols chloramphenicolstreptogramins quinupristin-dalfopristintetracyclines doxycycline
minocyclinetetracycline
glycylcycline tigecycline
Glo
ssar
y I
January 2005 Vol. 25 No. 1
©Clinical and Laboratory Standards Institute. All rights reserved.80
Glossary II. Abbreviations/Routes of Administration/Drug Class for Antimicrobial Agents Listedin M100-S15
Glo
ssar
y II
Antimicrobial Agent Agent Abbreviationa Routes of Administrationb Drug Class
PO IM IV
Amikacin AN, AK, Ak, AMI, AMK
X X aminoglycoside
Amoxicillin AMX, Amx, AMOX, AC
X penicillin
Amoxicillin-clavulanic acid AMC, Amc, A/C, AUG,
Aug, XL, AML
X β-lactam/β-lactamase inhibitor
Ampicillin AM, Am, AMP X X X penicillinAmpicillin-sulbactam SAM, A/S,
AMS, ABX β-lactam/β-lactamase
inhibitorAzithromycin AZM, Azi, AZI, AZ X X macrolideAzlocillin AZ, Az, AZL X X penicillinAztreonam ATM, AZT, Azt, AT, AZM X monobactam
Carbenicillin (indanyl salt)
Carbenicillin
CB, Cb, BAR X
X X
penicillin
Cefaclor CEC, CCL, Cfr, FAC, CF X cephem
Cefadroxil CFR, FAD X cephemCefamandole MA, CM, Cfm, FAM X X cephemCefazolin CZ, CFZ, Cfz, FAZ, KZ X X cephemCefdinir CDR, Cdn, DIN, CD, CFD X cephemCefditoren CDN X cephemCefepime FEP, Cpe, PM, CPM X X cephemCefetamet CAT, FET X cephemCefixime CFM, FIX, Cfe, IX X cephemCefmetazole CMZ, CMZS, CMT X X cephemCefonicid CID, Cfc, FON, CPO X X cephemCefoperazone CFP, Cfp, CPZ, PER, FOP,
CPX X cephem
Cefotaxime CTX, TAX, Cft, FOT, CT X X cephemCefotetan CTT, CTN, Ctn, CTE,
TANS, CNX X cephem
Cefoxitin FOX, CX, Cfx, FX X X cephemCefpodoxime CPD, Cpd, POD, PX X cephemCefprozil CPR, CPZ, FP X cephemCeftazidime CAZ, Caz, TAZ, TZ X X cephemCeftibuten CTB, TIB, CB X cephemCeftizoxime ZOX, CZX, CZ, Cz, CTZ,
TIZX X cephem
Ceftriaxone CRO, CTR, FRX, Cax, AXO, TX
X X cephem
Cefuroxime (axetil)
Cefuroxime (sodium)
CXM, CFX, ROX, Crm, FUR, XM
X
X X
cephem
Cephalexin CN, LEX, CFL X cephemCephalothin CF, Cf, CR, CL, CEP,
CE, KFX cephem
For Use With M2-A8–Disk Diffusion M100-S15
©Clinical and Laboratory Standards Institute. All rights reserved. 81
Glossary II. (Continued)
Glo
ssar
y II
Antimicrobial Agent Agent Abbreviationa
Routes of Administrationb
Drug Class
PO IM IVCephapirin CP, HAP X X cephemCephradine RAD, CH X cephemChloramphenicol C, CHL, CL X X phenicolCinoxacin CIN, Cn X quinoloneCiprofloxacin CIP, Cp, CI X X fluoroquinoloneClarithromycin CLR, CLM,
CLA, Cla, CHX macrolide
Clinafloxacin CFN, CLX, LF X X fluoroquinoloneClindamycin CC, CM, CD, Cd, CLI,
DAX X X lincosamide
Colistin CL, CS, CT X lipopeptideDalbavancin DAL X glycopeptideDaptomycin DAP X lipopeptideDicloxacillin DX, DIC X penicillinDirithromycin DTM, DT X macrolideDoripenem DOR X carbapenemErtapenem ETP X X carbapenemErythromycin E, ERY, EM X X macrolideFleroxacin FLE, Fle, FLX, FO X X fluoroquinoloneFosfomycin FOS, FF, FO, FM X fosfomycinGarenoxacin GRN X X quinoloneGatifloxacin GAT X X fluoroquinoloneGemifloxacin GEM X fluoroquinoloneGentamicinGentamicin synergy
GM, Gm, CN, GENGM500, HLG, Gms
X X aminoglycoside
Grepafloxacin GRX, Grx, GRE, GP X fluoroquinolone
Imipenem IPM, IMI, Imp, IP X carbapenemKanamycin K, KAN, HLK, KM X X aminoglycosideLevofloxacin LVX, Lvx,
LEV, LEVO, LEX X fluoroquinolone
Linezolid LNZ, LZ, LZD X X oxazolidinoneLomefloxacin LOM, Lmf X fluoroquinoloneLoracarbef LOR, Lor, LO X cephemMecillinam MEC X penicillinMeropenem MEM, Mer, MERO,
MRP, MPX carbapenem
Methicillin DP, MET, ME, SC X X penicillinMezlocillin MZ, Mz, MEZ X X penicillinMinocycline MI, MIN, Min, MN,
MNO, MC, MHX X tetracycline
Moxalactam MOX X X cephemMoxifloxacin MXF X X fluoroquinoloneNafcillin NF, NAF, Naf X X penicillinNalidixic acid NA, NAL X quinoloneNetilmicin NET, Nt, NC X X aminoglycosideNitrofurantoin F/M, FD, Fd, FT,
NIT, NI, FX nitrofurantoin
Norfloxacin NOR, Nxn, NX X fluoroquinoloneOfloxacin OFX, OFL, Ofl, OF X X X fluoroquinoloneOritavancin ORI X glycopeptideOxacillin OX, Ox, OXS, OXA X X X penicillin
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Glossary II. (Continued)
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Antimicrobial Agent AgentAbbreviationa
Routes of Administrationb
Drug Class
PO IM IVPenicillin P, PEN, PV X X X penicillinPiperacillin PIP, PI, PP, Pi X X penicillin Piperacillin-tazobactam TZP, PTZ, P/T, PTc X β-lactam/β-lactamase
inhibitor combinationPolymyxin B PB X lipopeptideQuinupristin-dalfopristin SYN, Syn, QDA,
RPX streptogramin
Rifampin RA, RIF, Rif, RI,RD
X X ansamycin
Sparfloxacin SPX, Sfx, SPA, SO X fluoroquinolone
Spectinomycin SPT, SPE, SC X X aminocyclitolStreptomycin
Streptomycin synergy
S, STR, StS, SM,
ST2000, HLS
X X aminoglycoside
Sulfonamides SSS, S3 X X folate pathway antagonist(some PO only)
Teicoplanin TEC, TPN, Tei,TEI, TP, TPL
X X glycopeptide
Telavancin TLV X glycopeptideTelithromycin TEL X ketolideTetracycline TE, Te, TET, TC X X tetracyclineTicarcillin TIC, TC, TI, Ti X X penicillinTicarcillin-clavulanic acid TIM, Tim, T/C,
TCC, TLcX β-lactam/β-lactamase
inhibitorTigecycline TGC X glycylcyclineTobramycin NN, TM, TO, To,
TOBX X aminoglycoside
Trimethoprim TMP, T, TR, W X folate pathway inhibitorTrimethoprim-sulfamethoxazole
SXT, SxT, T/S, TS,COT
X X folate pathway inhibitor
Trospectinomycin X X aminocyclitolTrovafloxacin TVA, Tva, TRV, TV X X fluoroquinolone
Vancomycin VA, Va, VAN X X glycopeptide
a Abbreviations assigned to one or more diagnostic products in the U.S.b As available in the U.S.
PO per OS (oral)IM intramuscularIV intravenous
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List of Identical Abbreviations Used for More Than One Antimicrobial Agent inU.S. Diagnostic Products
Agent Abbreviation Antimicrobial Agents for Which RespectiveAbbreviation is Used
AZM Azithromycin, AztreonamAZ Azithromycin, Azlocillin
CB, Cb Ceftibuten, CarbenicillinCFR, Cfr Cefaclor, Cefadroxil
CF, Cf Cefaclor, CephalothinCM Clindamycin, Cefamandole
CFM, Cfm Cefixime, CefamandoleCZ, Cz Ceftizoxime, CefazolinCD, Cd Clindamycin, Cefdinir
CPZ Cefprozil, CefoperazoneCP, Cp Cephapirin, Cefoperazone, CiprofloxacinCN, Cn Cephalexin, Cefotetan, Cinoxacin, Gentamicin
CFX, Cfx Cefoxitin, CefuroximeCL Cephalothin, ChloramphenicolCH Clarithromycin, CephradineDX Doxycycline, DicloxacillinFO Fleroxacin, FosfomycinSC Spectinomycin, MethicillinSO Sparfloxacin, OxacillinTC Tetracycline, Ticarcillin
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Summary of Comments and Subcommittee Responses
M100-S14: Performance Standards for Antimicrobial Susceptibility Testing; Fourteenth InformationalSupplement (M2-Disk Diffusion)
1. Amoxicillin-sulbactam is marketed and prescribed in more than 20 countries all over the world. The breakpointscannot be extrapolated from the results of amoxicillin-clavulanate or ampicillin-sulbactam, even though crosssusceptibility among these drugs does exist. We feel that this point should be clarified in Clinical andLaboratory Standards Institute/NCCLS recommendations.
• Clinical and Laboratory Standards Institute is able to establish interpretive criteria only forantimicrobial agents which have been presented and discussed at CLSI meetings. If sufficient dataconforming to CLSI/NCCLS document M23—Development of In Vitro Susceptibility Testing Criteria andQuality Control Parameters for amoxicillin-sulbactam were presented to the subcommittee, we wouldconsider a request for interpretive criteria for that compound.
2. Sodium fosfomycin (not trometamol) is commonly used in Latin America for the treatment of severalinfections. Seven Latin American countries use cefoperazone-sulbactam for severe infections. No breakpointsare available for either compound.
• There are breakpoints in the current documents for Enterococcus faecalis and Escherichia coli for oralfosfomycin. If sufficient data conforming to CLSI/NCCLS document M23—Development of In VitroSusceptibility Testing Criteria and Quality Control Parameters for sodium fosfomycin and forcefoperazone-sulbactam were presented to the subcommittee, we would consider a request forinterpretive criteria for those compounds.
Table 2A
3. In South America, azithromycin (AZ) is at present largely used for the treatment of bacterial gastroenteritis dueto Salmonella spp. or Shigella spp. Breakpoints for the assay of AZ against these isolates should be included.
• If data conforming to CLSI/NCCLS document M23—Development of In Vitro Susceptibility TestingCriteria and Quality Control Parameters are presented to the subcommittee, we would consider addinginterpretive criteria for azithromycin for these organisms.
4. In South America, ESBLs are frequently found in Proteus mirabilis, Salmonella (non-typhi) and Shigella spp.Why does the Clinical and Laboratory Standards Institute consider only E. coli and Klebsiella spp. for ESBLdetection? Use of cefotaxime, ceftazidime, and cefepime should be encouraged for the phenotypic detection ofESBLs.
• We have recently carried out a study to determine the suitability of the ESBL screening and confirmationtests for P. mirabilis and that organism has been added to the ESBL table in Table 2A in M2 and M7 alongwith E. coli, K. pneumoniae, and K. oxytoca. Although the use of cefepime for characterizing ESBLs hasbeen described, criteria for the use of cefepime with and without clavulanate has not been studiedsufficiently to date to be included in the document. The same is true for Salmonella and Shigella spp.,which precludes adding them to the list at this time.
Table 2B
5. Why is only levofloxacin included as a new fluoroquinolone for Stenotrophomonas maltophilia testing by diskdiffusion? What about moxifloxacin and gatifloxacin?
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Clinical and Laboratory Standards Institute consensus procedures include an appeals process thatis described in detail in Section 8 of the Administrative Procedures. For further information,contact the Executive Offices or visit our website at www.clsi.org.
For Use With M2-A8–Disk Diffusion M100-S15
©Clinical and Laboratory Standards Institute. All rights reserved. 85
• In recent studies to develop disk diffusion criteria for S. maltophilia, only agents with clinical efficacynoted in the published literature were included. At this time, clinical data to support the use ofmoxifloxacin and/or gatifloxacin against S. maltophilia are limited or do not exist. If sufficient dataconforming to CLSI/NCCLS document M23—Development of In Vitro Susceptibility Testing Criteria andQuality Control Parameters for testing of other agents against S. maltophilia were presented to thesubcommittee, we would consider a request for interpretive criteria for those compounds.
6. Why should ceftazidime and not cefepime be tested by disk diffusion vs. Burkholderia cepacia?
• In recent studies to develop disk diffusion criteria for B. cepacia, only agents where clinical efficacy hadbeen suggested in the published literature were included. If sufficient data conforming to CLSI/NCCLSdocument M23—Development of In Vitro Susceptibility Testing Criteria and Quality Control Parametersfor testing of other agents against B. cepacia were presented to the subcommittee, we would consider arequest for interpretive criteria for those compounds.
Table 2C
7. We currently do not perform any definitive identification testing on any coagulase-negative staphylococci(CoNS). We do a rapid latex, and if negative, report as CoNS. In M100-S14, the text states that testing formecA or PBP 2a is to be performed on non-Staphylococcus epidermidis isolates, are you then saying that Imust now perform definitive identification for all coagulase-negative staphylococci?
• The Clinical and Laboratory Standards Institute does not require identification of coagulase-negativestaphylococci to the species level, with two exceptions: 1) laboratories should identify S. saprophyticusin urinary isolates for which susceptibility testing is not recommended; and 2) laboratories shouldidentify S. lugdunensis, an uncommon pathogen, but one that can cause endocarditis. For laboratoriesthat do not wish to identify all coagulase-negative staphylococci to species level, S. saprophyticus and S.lugdunensis can be easily identified using a few simple tests (Clinical Microbiology ProceduresHandbook, 2nd edition, 2004, ASM Press; Manual of Clinical Microbiology, 8th edition 2003, ASMPress). S. saprophyticus is novobiocin resistant at ≤≤16 mm on Mueller-Hinton agar. S. lugdunensis canbe identified using pyrrolidonyl arylamidase and ornithine decarboxylase. S. lugdunensis is stronglyPYR positive and ornithine decarboxylase positive. A simple scheme for identification of S. lugdunensishas also been proposed by Schnitzler, et al. (J Clin Microbiol, 36:812-13, 1998).
8. If we have a patient with pure culture of coagulase-negative staphylococci from a lower respiratory specimen,a wound, or a catheter tip, are you suggesting that because these are not sterile sites, we should not beperforming the mecA testing? Is this mecA test ONLY for sterile site specimens, or is it for serious infectionsand sites? You know that a terminology of “serious infection” falls into a gray zone.
• The definition of serious infection should be institution-specific. Laboratories, in consultation withinfectious disease clinicians, should decide which specimens warrant additional testing of CoNS formecA or PBP 2a. For example, isolates from endocarditis and osteomyelitis would fall into this category.
9. I have a question regarding the use of the cefoxitin disk to predict for oxacillin resistance in Staphylococcusspecies as outlined in M100-S14. The following two statements in the document are in themselves easilyunderstood.
M100-S14, page 104, Warning 2, states, “For oxacillin-resistant Staphylococcus aureus and coagulase-negative staphylococci, all penicillins, cephems, and other ß-lactams...may appear active in vitro but are noteffective clinically. Results for these drugs should be reported as resistant or should not be reported.”
M100-S14, page 105, comment 10, states, “For oxacillin-susceptible strains, results for parenteral and oralcephems, ß-lactam/ß-lactamase inhibitor combinations, and carbapenems, if tested, should be reportedaccording to the results generated using routine interpretative criteria.”
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It is when I attempt to combine the information that I am becoming confused.
Let’s say that I have a Staphylococcus species with MICs for oxacillin and cefazolin which interpret asresistant, but the cefoxitin disk diffusion interpretation is susceptible. Do I change the cephems, and other ß-lactams to susceptible as well, following the logic of page 104, warning 2, or do I leave the cephems and otherß-lactams as resistant in accordance with comment 10 on page 105?
• Testing of staphylococci against cefazolin and cefoxitin using an MIC method is not recommended.Determination of oxacillin susceptibility is best done with oxacillin when using an MIC method and bycefoxitin when doing disk diffusion. These phenotypic test methods correlate best with the presence orabsence of the mecA gene, which is associated with oxacillin resistance. Susceptibility to cefazolin andother cephems should be predicted using oxacillin when performing an MIC test or cefoxitin (foroxacillin) when performing disk diffusion.
10. If I were to not perform any definitive identification on coagulase-negative staphylococci isolates andperformed the mecA test, what are the implications if the isolate was truly a Staphylococcus epidermidis?
• Tests for mecA and the gene product PBP 2a are accurate and rapid methods for detecting oxacillinresistance in S. aureus and all coagulase-negative staphylococci including S. epidermidis.
11. In Table 2C (M7), comment 10, is this mecA testing for coagulase-negative staphylococci isolates only, or isit also for Staphylococcus aureus?
• See the response to question 10.
12. Why is CLSI moving to the cefoxitin disk screen test for oxacillin resistance detection in staphylococci? It isclear that there is better correlation between oxacillin resistance and mecA detection or the latex test for PBP2a. This information should be stated in the CLSI/NCCLS recommendations.
• For S. aureus and S. lugdunensis, the cefoxitin disk test is comparable to the oxacillin disk test forprediction of mecA-mediated resistance to oxacillin; however, the cefoxitin disk test is easier to read andtherefore it is the preferred method. For coagulase-negative staphylococci, oxacillin interpretive criteriacorrelate with the presence or absence of the gene encoding oxacillin resistance (mecA) in S. epidermidis;however, these interpretive criteria may overcall resistance for other coagulase-negative staphylococci(e.g., S. saprophyticus). For coagulase-negative staphylococci, the cefoxitin disk test has greaterspecificity than oxacillin and equal sensitivity, although it may miss some strains of mecA-positive S.simulans. It is true, however, that mecA detection and the latex test for PBP 2a are the most accuratepredictors of mecA-mediated resistance and these tests should be used when available and clinicallyrelevant. However, not all laboratories have the resources to perform these tests.
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For Use With M7-A6–MIC Testing M100-S15
©Clinical and Laboratory Standards Institute. All rights reserved. 87
Introduction to Tables 1 Through 1B and 2A Through 2L for Use With M7-A6—MIC Testing
I. Selecting Antimicrobial Agents for Testing and Reporting
A. Selection of the most appropriate antimicrobial agents to test and to report is a decision best madeby each clinical laboratory in consultation with the infectious disease practitioners and thepharmacy, as well as the pharmacy and therapeutics and infection control committees of themedical staff. The recommendations here for each organism group comprise agents of provenefficacy that show acceptable in vitro test performance. Considerations in the assignment of agentsto specific test/report groups include clinical efficacy, prevalence of resistance, minimizingemergence of resistance, cost, FDA indications, and current consensus recommendations for first-choice and alternative drugs, in addition to the specific issues described. Tests of selected agentsmay be useful for infection control purposes.
B. The listing of drugs together in a single box designates clusters of comparable agents that need notbe duplicated in testing, because interpretive results are usually similar and clinical efficacycomparable. In addition, an “or” designates a related group of agents that has an almost identicalspectrum of activity and interpretive results, and for which cross-resistance and susceptibility arenearly complete. Therefore, usually only one of the agents within each selection box (cluster orrelated group) need be selected for testing. Agents reported must be tested, unless reporting basedon testing another agent provides a more accurate result (e.g., susceptibility of staphylococci tocefazolin or cephalothin based on oxacillin testing), and they usually should match those includedin the hospital formulary; or else the report should include footnotes indicating the agents thatusually show comparable interpretive results. Unexpected results should be considered forreporting (e.g., resistance of Enterobacteriaceae to third-generation cephalosporins or imipenem).
On the following pages, you will find:
1. Tables 1 and 1A—Suggested groupings of U.S. FDA-approved antimicrobial agents thatshould be considered for routine testing and reporting by clinical microbiologylaboratories.
2. For each organism group, an additional table (Tables 2A through 2L) that contains:a. Recommended testing conditions.b. Minimal QC recommendations. (See also the M7-A6 text document, Section 12.)c. General comments for testing the organism group and specific comments for testing
particular drug/organism combinations.d. Suggested agents that should be considered for routine testing and reporting by
clinical microbiology laboratories as specified in Tables 1 and 1A (test/report groupsA, B, C, U; the latter for “urine”).
e. Additional drugs that have an approved indication for the respective organism group,but would generally not warrant routine testing by a clinical microbiology laboratoryin the United States (test/report group O for “other”; test/report group Inv. for“investigational” [not yet FDA approved]).
f. Minimal inhibitory concentration (MIC) interpretive standards.
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C. Test/Report Groups
1. As listed in Tables 1 and 1A, agents in Group A are considered appropriate for inclusionin a routine, primary testing panel, as well as for routine reporting of results for thespecific organism groups.
2. Group B comprises agents that are important clinically, particularly for nosocomialinfections, and they may warrant primary testing. However, they may be reported onlyselectively, such as when the organism is resistant to agents of the same class, as in GroupA. Other indications for reporting the result might include a selected specimen source(e.g., a third-generation cephalosporin for enteric bacilli from cerebrospinal fluid [CSF]or trimethoprim-sulfamethoxazole for urinary tract isolates); a polymicrobial infection;infections involving multiple sites; on request in case of allergy, intolerance, or failure torespond to an agent in Group A; or for reporting to infection control as an epidemiologicaid.
3. Group C comprises alternative or supplemental antimicrobial agents that may requiretesting in those institutions that harbor endemic or epidemic strains resistant to several ofthe primary drugs (especially in the same class, e.g., β-lactams or aminoglycosides); fortreatment of patients allergic to primary drugs; for treatment of unusual organisms (e.g.,chloramphenicol for extraintestinal isolates of Salmonella spp. or vancomycin-resistantenterococci); or for reporting to infection control as an epidemiologic aid.
4. Group U (“urine”) lists certain antimicrobial agents (e.g., nitrofurantoin and certainquinolones) that are used only or primarily for treating urinary tract infections. Theseagents should not be routinely reported against pathogens recovered from other sites ofinfection. Other agents with broader indications may be included in Group U for specificurinary pathogens (e.g., P. aeruginosa).
5. Group O (“other”) includes agents that have a clinical indication for the organism groupbut are generally not candidates for routine testing and reporting in the United States.
6. Group Inv. (“investigational”) includes agents that are investigational for the organismgroup and have not yet been approved by the FDA.
D. Selective Reporting
Each laboratory should decide which agents in the tables to report routinely (Group A) and whichmight be reported only selectively (from Group B), in consultation with the infectious diseasepractitioners and the pharmacy, as well as the pharmacy and the therapeutics and infection controlcommittees of the medical staff of the hospital. Selective reporting should help improve theclinical relevance of test reports and help minimize the selection of multiresistant nosocomialstrains by overuse of broad-spectrum agents. Results for Group B agents not reported routinelyshould be available on request, or they may be reported for selected specimens. Unexpectedresistance, when confirmed, should be reported (e.g., resistance to a secondary agent butsusceptibility to a primary agent).
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II. Reporting MIC Results
A. The MIC values determined as described in this document may be reported directly to cliniciansfor patient-care purposes. However, it is essential for an understanding of the data by all cliniciansthat an interpretive category result also be provided routinely. Recommended interpretivecategories for various MIC values are included in tables for each organism group and are basedon evaluation data as described in CLSI/NCCLS document M23—Development of In VitroSusceptibility Testing Criteria and Quality Control Parameters.
Recommended interpretive criteria are based on usual dosage regimens and routes ofadministration in the U.S.
1. Susceptible (S)
The “susceptible” category implies that an infection due to the strain may be appropriatelytreated with the dosage of antimicrobial agent recommended for that type of infection andinfecting species, unless otherwise contraindicated.
2. Intermediate (I)
The “intermediate” category includes isolates with antimicrobial agent MICs thatapproach usually attainable blood and tissue levels and for which response rates may belower than for susceptible isolates. The “intermediate” category implies clinicalapplicability in body sites where the drugs are physiologically concentrated (e.g.,quinolones and β-lactams in urine) or when a high dosage of a drug can be used (e.g., β-lactams). The “intermediate” category also includes a buffer zone which should preventsmall, uncontrolled technical factors from causing major discrepancies in interpretations,especially for drugs with narrow pharmacotoxicity margins.
3. Resistant (R)
Resistant strains are not inhibited by the usually achievable systemic concentrations of theagent with normal dosage schedules and/or fall in the range where specific microbialresistance mechanisms are likely (e.g., β-lactamases) and clinical efficacy has not beenreliable in treatment studies.
B. For organisms excluded from Tables 2A through 2L (e.g., Campylobacter spp., Corynebacteriumspp., Bacillus spp.) studies are not yet adequate to develop reproducible, definitive standards tointerpret results. These organisms may require different media, different atmospheres ofincubation, or show marked strain-to-strain variation in growth rate. For these microorganisms,consultation with an infectious disease specialist is recommended for guidance in determining theneed for susceptibility testing and in the interpretation of results. Published reports in the medicalliterature and current consensus recommendations for therapy of uncommon microorganisms mayobviate the need for testing. If necessary, a dilution method usually will be the most appropriatetesting method, and this may require submitting the organism to a reference laboratory.
If only “S” criteria are specified:For some organism/antimicrobial combinations, the absence of resistant strains precludesdefining any results categories other than “susceptible.” For strains yielding resultssuggestive of a “nonsusceptible” category, organism identification and antimicrobialsusceptibility test results should be confirmed. Subsequently, the isolates should be savedand submitted to a reference laboratory that will confirm results using a CLSI/NCCLSreference dilution method.
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C. Policies regarding the generation of cumulative antibiograms should be developed in concert withthe infectious disease service, infection control personnel, and the pharmacy and therapeuticscommittee. Under most circumstances, the percentage of susceptible and intermediate resultsshould not be combined into the same statistics.
III. Therapy-Related Comments
Some of the comments in the tables relate to therapy concerns. These are denoted with an Rxsymbol. It may be appropriate to include some of these comments (or modification thereof) on thepatient report. An example would be inclusion of a comment on enterococcus susceptibilityreports from blood cultures that “enterococcal endocarditis requires combined therapy with high-dose penicillin or high-dose ampicillin or vancomycin or teicoplanin plus gentamicin orstreptomycin for bactericidal action.”
Antimicrobial dosage regimens often vary widely among practitioners and institutions. In somecases, the MIC interpretive criteria rely on pharmacokinetic-pharmacodynamic data using specifichuman dosage regimens. In cases where specific dosage regimens are important for properapplication of breakpoints, a therapy-related comment is included.
IV. Verification of Patient Results
Multiple test parameters are monitored by following the quality control recommendationsdescribed in this standard. However, acceptable results derived from testing quality control strainsdo not guarantee accurate results when testing patient isolates. It is important to review all of theresults obtained from all drugs tested on a patient’s isolate prior to reporting the results. Thisshould include but not be limited to ensuring that: 1) the antimicrobial susceptibility results areconsistent with the identification of the isolate; 2) the results from individual agents within aspecific drug class follow established hierarchy of activity rules (e.g., third-generation cephemsare more active than first- or second-generation cephems against Enterobacteriaceae); and 3) theisolate is susceptible to those agents for which resistance has not been documented (e.g.,vancomycin and Streptococcus spp.) and for which only “susceptible” interpretive criteria exist inM100.
Unusual or inconsistent results should be verified by checking for the following: 1) transcriptionerrors; 2) contamination of the test (recheck purity plates, etc.); 3) use of a defective panel, plate,or card (e.g., broken, underfilled); and 4) previous results on the patient (e.g., Did the patient havethe same isolate with an unusual antibiogram previously?) If a reason for the unusual orinconsistent result cannot be ascertained, a repeat of the susceptibility test or the identification orboth of these is in order. Sometimes it is helpful to use an alternative test method for the repeattest. A suggested list of results that may require verification is included in Table 8. Each laboratorymust develop its own policies for verification of unusual or inconsistent antimicrobialsusceptibility test results. This list should emphasize those results that are highly likely to impactpatient care.
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V. Warning
Some of the comments in the tables relate to dangerously misleading results that can occur when certainantimicrobial agents are tested and reported as susceptible against specific organisms. These are denotedwith the word “Warning.”
“Warning”: The following antimicrobial agent/organism combinations may appear active in vitro butare not effective clinically and should not be reported as susceptible.
Location Organism Antimicrobial Agents That Must Not be Reported as Susceptible
Table 2A Salmonella spp., Shigella spp. 1st- and 2nd-generation cephalosporins, andaminoglycosides
Table 2C oxacillin-resistant Staphylococcusspp.
all penems, cephems, and other ß-lactamssuch as amoxicillin-clavulanic acid,piperacillin-tazobactam, and imipenem
Table 2D Enterococcus spp. aminoglycosides (except highconcentrations), cephalosporins,clindamycin, and trimethoprim-sulfamethoxazole
Table 2K (Table 2A) Yersinia pestis β-lactam antimicrobial agentsTable 7 Listeria spp. cephalosporins
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Tabl
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©Clinical and Laboratory Standards Institute. All rights reserved.
Table 1. Suggested Groupings of U.S. FDA-Approved Antimicrobial Agents That Should BeConsidered for Routine Testing and Reporting on Nonfastidious Organisms by Clinical MicrobiologyLaboratories
GR
OU
PA
PRIM
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TEST
AN
D R
EPO
RT
Enterobacteriaceaeg Pseudomonas aeruginosaand Other Non-Enterobacteriaceaej
Staphylococcus spp. Enterococcus spp.n
Ampicillin g Ceftazidime Oxacillinl Penicillino or ampicillin
Cefazolina
Cephalothina
Gentamicin Penicillinl
Gentamicin Mezlocillin or ticarcillin
Piperacillin
Amikacin Amikacin
Azithromycind or
clarithromycind or
erythromycind
Daptomycins
Linezolid Quinupristin-
dalfopristinr
Amoxicillin-clavulanic acid orampicillin-sulbactam
Piperacillin-tazobactamTicarcillin-clavulanic acid
Cefepime Vancomycinp
Cefamandole orcefonicid orcefuroxime
CefoperazoneAztreonam
Clindamycind
DaptomycinCiprofloxacinLevofloxacin
Linezolid Telithromycind
Cefepime ImipenemMeropenem
Trimethoprim-sulfamethoxazole
CefmetazoleCefoperazoneg
CefotetanCefoxitin
Ticarcillin-clavulanic acidk Vancomycin
Tobramycin
Cefotaximeg, h, i orceftizoxime g, i orceftriaxoneg, h, i
Trimethoprim-sulfamethoxazolek
Ciprofloxacing orlevofloxacing
ErtapenemImipenem or
meropenemMezlocillin or
piperacillinTicarcillinTrimethoprim-sulfamethoxazoleg
AztreonamCeftazidime(Both are helpful indicators ofextended-spectrum β-lactamases.)i
Cefotaximek
orceftriaxone
k
Chloramphenicold Gentamicin (high-level resistance screen only)
Chloramphenicold, k
Netilmicin Ciprofloxacin orlevofloxacin orofloxacin
Gatifloxacin ormoxifloxacin
Streptomycin(high-level resistancescreen only)
Chloramphenicold, g Gentamicin Chloramphenicold
Erythromycind
Rifampinc
Tetracyclineb
(These agents may betested for VRE.)q
Kanamycin Quinupristin-dalfopristinmNetilmicin
Tetracyclineb Rifampinc
Tobramycin Tetracyclineb
GR
OU
PC
f
SUPP
LEM
ENTA
LR
EPO
RT
SELE
CTI
VELY
GR
OU
PU
SUPP
LEM
ENTA
LFO
R U
RIN
E O
NLY
Carbenicillin Carbenicillin Lomefloxacin ornorfloxacin
CiprofloxacinLevofloxacinNorfloxacin
Cinoxacin Lomefloxacin or
norfloxacin orofloxacin
Gatifloxacin Ceftizoximek Nitrofurantoin
Loracarbef Lomefloxacin ornorfloxacin orofloxacin
NitrofurantoinNitrofurantoin Sulfisoxazole Sulfisoxazole Trimethoprim Trimethoprim Sulfisoxazole Tetracyclineb
Tetracyclineb,k
GR
OU
PB
e
PRIM
ARY
TEST
REP
OR
T SE
LEC
TIVE
LY
For Use With M7-A6–MIC Testing M100-S15Table 1. (Continued)
GR
OU
PA
PRIM
ARY
TEST
AN
D R
EPO
RT
Acinetobacter spp.j Burkholderia cepacia j Stenotrophomonas maltophilia j
Ceftazidime Trimethoprim-sulfamethoxazole
Trimethoprim-sulfamethoxazole
ImipenemMeropenem
AmikacinGentamicinTobramycin
Ceftazidime CeftazidimeChloramphenicol Chloramphenicol
Levofloxacin Levofloxacin
Ampicillin-sulbactamPiperacillin-tazobactamTicarcillin-clavulanate
Meropenem Minocycline Minocycline Ticarcillin-clavulanate
Ticarcillin-clavulanateCefepime
CefotaximeCeftriaxone
CiprofloxacinGatifloxacinLevofloxacin
DoxycyclineMinocyclineTetracycline
MezlocillinPiperacillinTicarcillin
Trimethoprim-sulfamethoxazole
Polymyxin B
GR
OU
PC
f
SUPP
LEM
ENTA
LR
EPO
RT
SELE
CTI
VELY
GR
OU
PB
e
PRIM
ARY
TEST
REP
OR
T SE
LEC
TIVE
LY
GR
OU
PU
SUPP
LEM
ENTA
LFO
R U
RIN
E O
NLY
©Clinical and Laboratory Standards Institute. All rights reserved. 93
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Table 1. (Continued)
NOTE 1: Selection of the most appropriate antimicrobial agents to test and to report is a decision made bestby each clinical laboratory in consultation with the infectious disease practitioners and the pharmacy,as well as the pharmacy and therapeutics and infection control committees of the medical staff. Thelists for each organism group comprise agents of proven efficacy that show acceptable in vitro testperformance. Considerations in the assignment of agents to Groups A, B, C, and U include clinicalefficacy, prevalence of resistance, minimizing emergence of resistance, cost, and current consensusrecommendations for first-choice and alternative drugs, in addition to the specific comments infootnotes “e” and “f.” Tests of selected agents may be useful for infection control purposes.
NOTE 2: The boxes in the table designate clusters of comparable agents that need not be duplicated in testing,because interpretive results are usually similar and clinical efficacy comparable. In addition, an “or”designates a related group of agents that has an almost identical spectrum of activity and interpretiveresults, and for which cross-resistance and susceptibility are nearly complete. Therefore, usually onlyone of the agents within each selection box (cluster or related group) need be selected for testing.Agents that are reported must be tested, unless reporting based on testing another agent provides amore accurate result (e.g., susceptibility of staphylococci to cefazolin or cephalothin based onoxacillin testing), and they usually should match those included in the hospital formulary; or else thereport should include footnotes indicating the agents that usually have comparable interpretiveresults. Finally, unexpected results should be considered for reporting (e.g., resistance ofEnterobacteriaceae to third-generation cephalosporins or imipenem).
NOTE 3: Information in boldface type is considered tentative for one year.
FootnotesGeneral Comments
a. Cephalothin can be used to represent cephalothin, cephapirin, cephradine, cephalexin, cefaclor, andcefadroxil. Cefazolin, cefuroxime, cefpodoxime, cefprozil, and loracarbef (urinary isolates only) may be testedindividually, because some isolates may be susceptible to these agents when resistant to cephalothin.
b. Organisms that are susceptible to tetracycline are also considered susceptible to doxycycline andminocycline. However, some organisms that are intermediate or resistant to tetracycline may be susceptibleto doxycycline or minocycline or both.
c. Rx: Rifampin should not be used alone for chemotherapy.
d. Not routinely reported on organisms isolated from the urinary tract.
e. Group B represents agents that may warrant primary testing but which should be reported only selectively,such as when the organism is resistant to agents of the same family in Group A. Other indications forreporting the result might include selected specimen sources (e.g., selected third-generation cephalosporinsfor isolates of enteric bacteria from CSF or trimethoprim-sulfamethoxazole for urinary tract isolates); statedallergy or intolerance, or failure to respond to an agent in Group A; polymicrobial infections; infectionsinvolving multiple sites with different microorganisms; or reports to infection control for epidemiologic aid.
“Warning”: The following antimicrobial agents should not be routinely reported forbacteria isolated from the CSF and which are included in this document. Theseantimicrobial agents are not the drugs of choice and may not be effective for treating CSFinfections caused by these organisms (i.e., the bacteria included in Tables 2A to 2J):
agents administered by oral route only1st- and 2nd-generation cephalosporins (except cefuroxime sodium)
clindamycinmacrolides
tetracyclinesfluoroquinolones
Tabl
e 1
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onfa
stid
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7-M
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For Use With M7-A6–MIC Testing M100-S15
95
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Table 1. (Continued)
f. Group C represents alternative or supplemental antimicrobial agents that may require testing in thoseinstitutions that harbor endemic or epidemic strains resistant to one or more of the primary drugs (especiallyin the same family, e.g., β-lactams or aminoglycosides), or for treatment of unusual organisms (e.g.,chloramphenicol for some Pseudomonas spp., and chloramphenicol, erythromycin, rifampin, and tetracyclinefor some vancomycin-resistant enterococci), or reporting to infection control as an epidemiologic aid.
Enterobacteriaceae
g. For fecal isolates of Salmonella and Shigella spp., only ampicillin, a fluoroquinolone, andtrimethoprim/sulfamethoxazole should be tested and reported routinely. In addition, chloramphenicol and athird-generation cephalosporin should be tested and reported for extraintestinal isolates of Salmonella spp.
h. Cefotaxime and ceftriaxone should be tested and reported on isolates from CSF in place of cephalothin andcefazolin.
i. Strains of Klebsiella spp. and E. coli that produce ESBLs may be clinically resistant to therapy with penicillins,cephalosporins, or aztreonam, despite apparent in vitro susceptibility to some of these agents. Some of thesestrains will show MICs above the normal susceptible population but below the standard breakpoints forcertain extended-spectrum cephalosporins or aztreonam; such strains may be screened for potential ESBLproduction by using the screening breakpoints listed at the end of Table 2A, Initial Screen Test. Other strainsmay test intermediate or resistant by standard breakpoints to one or more of these agents. In all strains withESBLs, the MICs for one or more of the extended-spectrum cephalosporins or aztreonam should decreasein the presence of clavulanic acid as described at the end of Table 2A, Phenotypic Confirmatory Test. For allconfirmed ESBL-producing strains, the test interpretation should be reported as resistant for all penicillins,cephalosporins, and aztreonam. (See Glossary I for specific agents included in the antimicrobial class,penicillins, and antimicrobial subclass, cephalosporins.)
Pseudomonas aeruginosa and Other Non-Enterobacteriaceae
j. Other non-Enterobacteriaceae include Pseudomonas spp., and other nonfastidious, glucose-nonfermenting,gram-negative bacilli except for Acinetobacter spp., Burkholderia cepacia, and Stenotrophomonasmaltophilia.
k. May be indicated for testing of some Pseudomonas spp. and other nonfastidious, glucose-nonfermenting, gram-negative bacilli.
Staphylococcus spp.
l. Penicillin-susceptible staphylococci are also susceptible to other penicillins, cephems, and carbapenemsapproved for use by the FDA for staphylococcal infections. Penicillin-resistant, oxacillin-susceptible strainsare resistant to penicillinase-labile penicillins but susceptible to other penicillinase-stable penicillins, β-lactam/β-lactamase inhibitor combinations, relevant cephems, and carbapenems. (See Glossary I for specificagents included in the antimicrobial class or antimicrobial subclass indicated). Oxacillin-resistantstaphylococci are resistant to all currently available β-lactam antibiotics. Thus, susceptibility or resistance toa wide array of β-lactam antibiotics may be deduced from testing only penicillin and oxacillin. Routine testingof other penicillins, β-lactamase inhibitor combinations, cephems, and carbapenems is not advised.
m. For reporting against methicillin-susceptible Staphylococcus aureus.
Enterococcus spp.
n. Warning: For Enterococcus spp., cephalosporins, aminoglycosides (except for high-level resistancescreening), clindamycin, and trimethoprim-sulfamethoxazole may appear active in vitro but are not effectiveclinically and should not be reported as susceptible.
January 2005 Vol. 25 No. 1
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Table 1. (Continued)
o. Penicillin susceptibility may be used to predict the susceptibility to ampicillin, amoxicillin, ampicillin-sulbactam, amoxicillin-clavulanic acid, piperacillin, and piperacillin-tazobactam for non-β-lactamase-producing enterococci. For blood and CSF isolates, a β-lactamase test is also recommended. Rx:Combination therapy of penicillin or ampicillin, plus an aminoglycoside, is usually indicated for seriousenterococcal infections, such as endocarditis.
p. Rx: Combination therapy with vancomycin plus an aminoglycoside is usually indicated for seriousenterococcal infections, such as endocarditis.
q. Because of limited alternatives, chloramphenicol, erythromycin, tetracycline (or doxycycline or minocycline),and rifampin may be tested for vancomycin-resistant enterococci, and consultation with an infectious diseasepractitioner is recommended.
r. For reporting against vancomycin-resistant Enterococcus faecium.
s. For reporting against vancomycin-susceptible Enterococcus faecalis.
For Use With M7-A6–MIC Testing M100-S15
97©Clinical and Laboratory Standards Institute. All rights reserved.
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98
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January 2005 Vol. 25 No. 1
Table 1A. Suggested Groupings of U.S. FDA-Approved Antimicrobial Agents That Should BeConsidered for Routine Testing and Reporting on Fastidious Organisms by Clinical MicrobiologyLaboratories
GR
OU
PA
PRIM
ARY
TEST
AN
D R
EPO
RT
Haemophilus spp.eNeisseria gonorrhoeaei Streptococcus pneumoniae
Streptococcus spp.Other ThanS. pneumoniae
Ampicilline, g Erythromycina Erythromycina, m, q
Penicillinj Penicillinl, n or ampicillinl, n
Trimethoprim-sulfamethoxazole
Trimethoprim-sulfamethoxazole
GR
OU
PB
b
PRIM
ARY
TEST
REP
OR
T SE
LEC
TIVE
LY
Ampicillin-sulbactamCefepime Cefotaximej or
ceftriaxonej
Chloramphenicolm
Cefuroxime sodium(parenteral)
Clindamycinm, q
Clindamycin
Cefotaximee orceftazidime orceftizoximee orceftriaxonee
Gatifloxacin GemifloxacinLevofloxacinMoxifloxacin OfloxacinSparfloxacin
Vancomycin
Chloramphenicole Meropenemj
Telithromycin
Meropeneme,h Tetracyclined
Vancomycinj
GR
OU
PC
C
SUPP
LEM
ENTA
LR
EPO
RT
SELE
CTI
VELY
Azithromycinf or clarithromycinf
Cefixime orcefotaxime orcefpodoxime orceftizoxime orceftriaxone
Amoxicillin or amoxicillin-clavulanic acid
Cefepime orcefotaxime orceftriaxoneAztreonam
Amoxicillin-clavulanic acidf
Cefaclorf or cefprozilf orloracarbeff
CefmetazoleCefotetanCefoxitinCefuroxime
Cefuroxime Daptomycinp
Cefdinirf orcefiximef orcefpodoximef
LevofloxacinOfloxacin
Cefonicid
Cefuroxime axetilf
(oral)Ciprofloxacin or
gatifloxacin orofloxacin
Chloramphenicol LinezolidQuinupristin-
dalfopristino
Ciprofloxacin or gatifloxacin or levofloxacin orlomefloxacin ormoxifloxacin orofloxacin orsparfloxacin
Gemifloxacin
Penicillin Ertapenem Imipenem
Linezolid
Ertapenem or imipenem
Spectinomycin Rifampink
Tetracyclined
Rifampin
Telithromycinf
Tetracyclined
For Use With M7-A6–MIC Testing M100-S15
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©Clinical and Laboratory Standards Institute. All rights reserved.
Table 1A. (Continued)
NOTE 1: Selection of the most appropriate antimicrobial agents to test and to report is a decision made bestby each clinical laboratory in consultation with the infectious disease practitioners and the pharmacy, aswell as the pharmacy and therapeutics and infection control committees of the medical staff. The lists foreach organism group comprise agents of proven efficacy that show acceptable in vitro test performance.Considerations in the assignment of agents to Groups A, B, and C include clinical efficacy, prevalence ofresistance, minimizing emergence of resistance, cost, and current consensus recommendations for first-choice and alternative drugs, in addition to the specific comments in footnotes “b” and “c.” Tests onselected agents may be useful for infection control purposes.
NOTE 2: The boxes in the table designate clusters of comparable agents that need not be duplicated intesting, because interpretive results are usually similar and clinical efficacy comparable. In addition, an“or” designates a related group of agents that has an almost identical spectrum of activity and interpretiveresults, and for which cross-resistance and susceptibility are nearly complete. Therefore, usually only oneof the agents within each selection box (cluster or related group) need be selected for testing. Agents thatare reported must be tested, unless reporting based on testing another agent provides a more accurateresult, and usually, they should match those included in the hospital formulary; or else the report shouldinclude footnotes indicating the agents that usually show comparable interpretive results. Lastly,unexpected results should be considered for reporting.
NOTE 3: Information in boldface type is considered tentative for one year. Footnotes
General Comments
a. Susceptibility and resistance to azithromycin, clarithromycin, and dirithromycin can be predicted bytesting erythromycin.
b. Group B represents agents that may warrant primary testing but which should be reported onlyselectively, such as when the organism is resistant to agents of the same class in Group A. Otherindications for reporting the result might include selected specimen sources (e.g., third-generationcephalosporin for isolates of Haemophilus influenzae from CSF); stated allergy or intolerance, or failureto respond to an agent in Group A; polymicrobial infections; infections involving multiple sites withdifferent microorganisms; or reports to infection control for epidemiologic aid.
c. Group C represents alternative or supplemental antimicrobial agents that may require testing in thoseinstitutions that harbor endemic or epidemic strains resistant to one or more of the primary drugs(especially in the same class, e.g., β-lactams), or for treatment of unusual organisms, or reporting toinfection control as an epidemiologic aid.
d. Organisms that are susceptible to tetracycline are also considered susceptible to doxycycline andminocycline.
Haemophilus spp.
e. Only results of testing with ampicillin, one of the third-generation cephalosporins, chloramphenicol, andmeropenem should be reported routinely with CSF isolates of H. influenzae.
f. Amoxicillin-clavulanic acid, azithromycin, clarithromycin, cefaclor, cefprozil, loracarbef, cefdinir, cefixime,cefpodoxime, cefuroxime axetil, and telithromycin are oral agents that may be used as empiric therapyfor respiratory tract infections due to Haemophilus spp. The results of susceptibility tests with theseantimicrobial agents are often not useful for management of individual patients. However, susceptibilitytesting of Haemophilus spp. with these compounds may be appropriate for surveillance or epidemiologicstudies.
“Warning”: The following antimicrobial agents should not be routinely reported forbacteria isolated from the CSF and which are included in this document. Theseantimicrobial agents are not the drugs of choice and may not be effective for treating CSFinfections caused by these organisms (i.e., the bacteria included in Tables 2A to 2J):
agents administered by oral route only1st- and 2nd-generation cephalosporins (except cefuroxime sodium)
clindamycinmacrolides
tetracyclinesfluoroquinolones
January 2005 Vol. 25 No. 1
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Table 1A. (Continued)
g. The results of ampicillin susceptibility tests should be used to predict the activity of amoxicillin. Themajority of isolates of H. influenzae that are resistant to ampicillin and amoxicillin produce a TEM-typeβ-lactamase. In most cases, a direct β-lactamase test can provide a rapid means of detecting ampicillinand amoxicillin resistance.
h. Clinical indications and relevant pathogens include bacterial meningitis and concurrent bacteremia inassociation with meningitis caused by H. influenzae (β-lactamase- and non-β-lactamase-producingstrains).
Neisseria gonorrhoeae
i. A β-lactamase test will detect one form of penicillin resistance in N. gonorrhoeae and also may be usedto provide epidemiologic information. Strains with chromosomally mediated resistance can be detectedonly by additional susceptibility testing, such as the disk diffusion method or the agar dilution MICmethod.
Streptococcus pneumoniae
j. Only results of testing with penicillin, cefotaxime, ceftriaxone, meropenem, and vancomycin should bereported routinely for CSF isolates of S. pneumoniae.
k. Rx: Rifampin should not be used alone for chemotherapy.
Streptococcus spp.
l. Rx: Penicillin or ampicillin intermediate isolates may require combined therapy with an aminoglycosidefor bactericidal action.
m. Not routinely reported for organisms isolated from the urinary tract.
n. Susceptibility testing of penicillins and other β-lactams approved by FDA for treatment of Streptococcuspyogenes or Streptococcus agalactiae is not necessary for clinical purposes and need not be doneroutinely, since as with vancomycin, resistant strains have not been recognized. Interpretive criteria areprovided for pharmaceutical development, epidemiology, or monitoring for emerging resistance. Anystrains found to be intermediate or resistant should be referred to a reference laboratory forconfirmation.
o. Report against S. pyogenes.
p. For reporting against beta-hemolytic streptococci only.
q. Rx: Recommendations for intrapartum prophylaxis for Group B streptococci are penicillin orampicillin. While cefazolin is recommended for penicillin-allergic women at low risk foranaphylaxis, those at high risk for anaphylaxis may receive clindamycin or erythromycin. GroupB streptococci are susceptible to ampicillin, penicillin, and cefazolin, but may be resistant toclindamycin and/or erythromycin. When a group B streptococcus is isolated from a pregnantwoman with severe penicillin allergy (high risk for anaphylaxis), clindamycin and erythromycinshould be tested and reported.
For Use With M7-A6–MIC Testing M100-S15
101©Clinical and Laboratory Standards Institute. All rights reserved.
Table 1B. Suggested Grouping of Antimicrobial Agents That Should Be Considered for Testingand Reporting on Potential Agents of Bioterrorism
Footnotes
General Comments
a. Organisms that are susceptible to penicillin are also considered susceptible to amoxicillin.
b. Organisms that are susceptible to tetracycline are also considered susceptible to doxycycline. However,some organisms that are intermediate or resistant to tetracycline may be susceptible to doxycycline.
Bacillus anthracis Yersinia pestis Burkholderia mallei Burkholderiapseudomallei
Penicillina Gentamicin Ceftazidime Amoxicillin-clavulanicacid
Doxycycline or tetracyclineb
Streptomycin Doxycycline or tetracyclineb
Ceftazidime
Ciprofloxacin Doxycycline or tetracyclineb
Imipenem Doxycycline or tetracyclineb
Ciprofloxacin Imipenem
Chloramphenicol Trimethoprim-sulfamethoxazole
Trimethoprim-sulfamethoxazole
GR
OU
PA
PRIM
ARY
TEST
AN
D R
EPO
RT
Tabl
e 1B
Sugg
este
d Po
tent
ial A
gent
sof
Bio
terr
oris
m G
roup
ings
M7-
MIC
102
Tabl
e 2A
Ente
roba
cter
iace
aeM
7-M
IC
©Clinical and Laboratory Standards Institute. All rights reserved.
Test
ing
Con
ditio
ns
Med
ium
:B
roth
dilu
tion:
Cat
ion-
adju
sted
Mue
ller-
Hin
ton
brot
h
(CA
MH
B)
Aga
r dilu
tion:
Mue
ller H
into
n ag
ar (M
HA
)In
ocul
um:
Gro
wth
met
hod
or d
irect
col
ony
susp
ensi
on, e
quiv
alen
t to
a 0.
5 M
cFar
land
sta
ndar
dIn
cuba
tion:
35 °
C ±
2 de
gree
s; a
mbi
ent a
ir; 1
6 to
20
hour
s.
Tabl
e 2A
. M
IC In
terp
retiv
e St
anda
rds
(µµg/
mL)
for
Ente
roba
cter
iace
ae
January 2005 Vol. 25 No. 1
Min
imal
QC
Rec
omm
enda
tions
(See
Tab
le 3
for a
ccep
tabl
e Q
C ra
nges
.)
Esch
eric
hia
coli
ATC
C®
259
22Es
cher
ichi
a co
liAT
CC
® 3
5218
(for
β-la
ctam
/β-la
ctam
ase
inhi
bito
rco
mbi
natio
ns)
Gen
eral
Com
men
ts(1
)Fo
rfe
cal
isol
ates
of
Salm
onel
laan
d Sh
igel
lasp
p.,
only
am
pici
llin,
a f
luor
oqui
nolo
ne,
and
trim
etho
prim
-sul
fam
etho
xazo
le s
houl
d be
tes
ted
and
repo
rted
rout
inel
y. I
n ad
ditio
n,ch
lora
mph
enic
ol a
nd a
third
-gen
erat
ion
ceph
alos
porin
sho
uld
be te
sted
and
repo
rted
for e
xtra
inte
stin
al is
olat
es o
f Sal
mon
ella
spp.
(2)
WA
RN
ING
: Fo
r Ye
rsin
ia p
estis
,stu
dies
hav
e de
mon
stra
ted
that
alth
ough
β-la
ctam
ant
imic
robi
al a
gent
s m
ay a
ppea
r ac
tive
in v
itro
they
lack
effi
cacy
in a
nim
al m
odel
s of
infe
ctio
n.Th
ese
antim
icro
bial
age
nts
shou
ld n
ot b
e re
porte
d as
sus
cept
ible
. Ref
er to
Tab
le 2
K fo
r tes
ting
of Y
. pes
tis.
NO
TE:
Info
rmat
ion
in b
oldf
ace
type
is c
onsi
dere
d te
ntat
ive
for o
ne y
ear.
Test
/Rep
ort
Gro
upA
ntim
icro
bial
Age
ntM
IC (µµ
g/m
L)In
terp
retiv
e St
anda
rdC
omm
ents
SI
RPE
NIC
ILLI
NS
AA
mpi
cilli
n≤
816
≥32
(3) C
lass
repr
esen
tativ
e fo
r am
pici
llin
and
amox
icill
in.
B B B
Mez
loci
llin
orpi
pera
cilli
nTi
carc
illin
≤16
≤16
≤16
32-6
432
-64
32-6
4
≥12
8≥
128
≥12
8U
Car
beni
cilli
n≤
1632
≥64
U/In
vM
ecill
inam
≤8
16≥
32(4
) For
use
aga
inst
E. c
olif
or u
rinar
y tra
ct is
olat
es o
nly.
ββ -LA
CTA
M/ββ
-LA
CTA
MA
SE IN
HIB
ITO
R C
OM
BIN
ATIO
NS
B B B B
Am
oxic
illin
-cla
vula
nic
acid
or
ampi
cilli
n-su
lbac
tam
Pip
erac
illin
-tazo
bact
amTi
carc
illin
-cla
vula
nic
acid
≤8/
4≤
8/4
≤16
/4≤
16/2
16/8
16/8
32/4
-64/
432
/2-6
4/2
≥32
/16
≥32
/16
≥12
8/4
≥12
8/2
103
Tabl
e 2A
Ente
roba
cter
iace
aeM
7-M
IC
©Clinical and Laboratory Standards Institute. All rights reserved.
For Use With M7-A6–MIC Testing M100-S15Ta
ble
2A. (
Con
tinue
d)Te
st/R
epor
tG
roup
Ant
imic
robi
al A
gent
MIC
(µµg/
mL)
Inte
rpre
tive
Stan
dard
Com
men
ts
SI
RC
EPH
EMS
(PA
REN
TER
AL)
(In
clud
ing
ceph
alos
porin
s I,
II, I
II, a
nd I
V. P
leas
e re
fer
to G
loss
ary
I.)(5
)W
AR
NIN
G:
For
Salm
onel
lasp
p. a
nd S
hige
llasp
p.,
first
- an
d se
cond
-gen
erat
ion
ceph
alos
porin
s m
ay a
ppea
r act
ive
in v
itro
but a
re n
ot e
ffect
ive
clin
ical
ly a
nd s
houl
d no
tbe
repo
rted
as s
usce
ptib
le.
(6)
Stra
ins
of K
lebs
iella
spp
. an
d E.
col
ith
at p
rodu
ce e
xten
ded-
spec
trum
bet
a-la
ctam
ase
(ES
BLs
) m
ay
be
clin
ical
ly
resi
stan
t to
th
erap
y w
ith
peni
cilli
ns,
ceph
alos
porin
s, o
r azt
reon
am, d
espi
te a
ppar
ent i
n vi
trosu
scep
tibili
ty to
som
e of
thes
eag
ents
. Som
e of
thes
e st
rain
s w
ill s
how
MIC
s ab
ove
the
norm
al s
usce
ptib
le p
opul
atio
nbu
t be
low
the
sta
ndar
d br
eakp
oint
s fo
r ce
rtain
ext
ende
d-sp
ectru
m c
epha
losp
orin
s or
aztre
onam
. S
uch
stra
ins
shou
ld b
e sc
reen
ed fo
r pot
entia
l ES
BL
prod
uctio
n by
usi
ng th
eE
SB
Lsc
reen
ing
brea
kpoi
nts
liste
d at
the
end
of th
is ta
ble
befo
re r
epor
ting
resu
lts fo
rpe
nici
llins
, ex
tend
ed-s
pect
rum
cep
halo
spor
ins,
or
aztre
onam
. O
ther
stra
ins
may
tes
tin
term
edia
te o
r res
ista
nt b
y st
anda
rd b
reak
poin
ts to
one
or m
ore
of th
ese
agen
ts. I
n al
lst
rain
s w
ith E
SB
Ls, t
he M
ICs
for o
ne o
r mor
e of
the
exte
nded
-spe
ctru
m c
epha
losp
orin
sor
azt
reon
am s
houl
d de
crea
se i
n th
e pr
esen
ce o
f cl
avul
anic
aci
d as
det
erm
ined
in
phen
otyp
ic c
onfir
mat
ory
test
ing.
For
all
conf
irmed
ES
BL-
prod
ucin
g st
rain
s, t
he t
est
inte
rpre
tatio
n sh
ould
be
repo
rted
as r
esis
tant
for
all
peni
cilli
ns,
ceph
alos
porin
s, a
ndaz
treon
am.
(See
tab
le l
ocat
ed a
t th
e en
d of
thi
s ta
ble
for
ES
BL
scre
enin
g an
dco
nfirm
ator
y te
sts.
R
efer
to
th
e gl
ossa
ry
for
defin
ition
s of
pe
nici
llins
an
dce
phal
ospo
rins.
) Th
e de
cisi
on t
o pe
rform
ES
BL
scre
enin
g te
sts
on a
ll ur
ine
isol
ates
shou
ld b
e m
ade
on a
n in
stitu
tiona
l bas
is, c
onsi
derin
g pr
eval
ence
, the
rapy
, and
infe
ctio
nco
ntro
l iss
ues.
(7)
R
outin
e sc
reen
ing
of
Prot
eus
mira
bilis
for
ESB
Lpr
oduc
tion
is
not
reco
mm
ende
d. H
owev
er, w
hen
it is
dee
med
clin
ical
ly re
leva
nt (e
.g.,
a ba
cter
emic
isol
ate)
the
ESB
Lsc
reen
tes
ting
MIC
bre
akpo
ints
, ce
ftazi
dim
e (M
IC ≥≥
2 µµ
g/m
L),
cefo
taxi
me
(MIC
≥≥ 2
µµg/
mL)
, or c
efpo
doxi
me
(MIC
≥≥ 2
µµg/
mL
rath
er th
an ≥≥
8 µµ
g/m
L)w
ill i
dent
ify p
resu
mpt
ive
ESB
Lpr
oduc
tion.
The
phe
noty
pic
conf
irmat
ory
test
usin
g ce
ftazi
dim
e an
d ce
fota
xim
e al
one
and
in c
ombi
natio
n w
ith c
lavu
lani
c ac
idca
n co
nfirm
ES
BL-
prod
ucin
g st
rain
s.
For
all
conf
irmed
ES
BL-
prod
ucin
g P.
mira
bilis
, the
test
inte
rpre
tatio
n sh
ould
be
repo
rted
as
resi
stan
t for
all
peni
cilli
ns,
ceph
alos
porin
s, a
nd a
ztre
onam
.
(8)
Ente
roba
cter
, C
itrob
acte
r, an
d Se
rratia
spp.
may
dev
elop
res
ista
nce
durin
gpr
olon
ged
ther
apy
with
thi
rd-g
ener
atio
n ce
phal
ospo
rins.
The
refo
re,
isol
ates
tha
t ar
ein
itial
ly s
usce
ptib
le m
ay b
ecom
e re
sist
ant
with
in t
hree
to
four
day
s af
ter
initi
atio
n of
ther
apy.
Tes
ting
of re
peat
isol
ates
may
be
war
rant
ed.
A AC
efaz
olin
C
epha
loth
in≤
8≤
816 16
≥32
≥32
(9)
Cep
halo
thin
can
be
used
to p
redi
ct a
ctiv
ity o
f cep
halo
thin
, cep
hapi
rin, c
ephr
adin
e,ce
phal
exin
, cef
aclo
r, an
d ce
fadr
oxil.
Cef
azol
in, c
efur
oxim
e, c
efpo
doxi
me,
cef
proz
il, a
ndlo
raca
rbef
(urin
ary
isol
ates
onl
y) m
ay b
e te
sted
indi
vidu
ally,
bec
ause
som
e is
olat
es m
aybe
sus
cept
ible
to th
ese
agen
ts w
hen
resi
stan
t to
ceph
alot
hin.
B B B
Cef
aman
dole
or
cefo
nici
d or
cefu
roxi
me
sodi
um (p
aren
tera
l)
≤8
≤8
≤8
16 16 16
≥32
≥32
≥32
BC
efep
ime
≤8
16≥
32B B B B
Cef
met
azol
e C
efop
eraz
one
C
efot
etan
C
efox
itin
≤16
≤16
≤16
≤8
32 32 32 16
≥64
≥64
≥64
≥32
104
Tabl
e 2A
Ente
roba
cter
iace
aeM
7-M
IC
©Clinical and Laboratory Standards Institute. All rights reserved.
January 2005 Vol. 25 No. 1
Tabl
e 2A
. (C
ontin
ued)
Test
/Rep
ort
Gro
upA
ntim
icro
bial
Age
ntM
IC (µµ
g/m
L)In
terp
retiv
e St
anda
rdC
omm
ents
SI
RC
EPH
EMS
(PA
REN
TER
AL)
(Con
tinue
d)B B B
Cef
otax
ime
orce
ftizo
xim
e or
ceftr
iaxo
ne
≤8
≤8
≤8
16-3
216
-32
16-3
2
≥64
≥64
≥64
(10)
Cef
otax
ime
and
ceftr
iaxo
ne s
houl
d be
test
ed a
nd re
porte
d on
isol
ates
from
CS
F in
pla
ce o
f cep
halo
thin
and
cef
azol
in.
See
com
men
t (6)
.C
Cef
tazi
dim
e≤
8 16
≥32
See
com
men
t (6)
.O
Mox
alac
tam
≤
8 16
-32
≥64
CEP
HEM
S (O
RA
L)B
Cef
urox
ime
axet
il (o
ral)
≤4
8-16
≥32
ULo
raca
rbef
≤8
16≥
32O
Cef
aclo
r≤
816
≥32
OC
efdi
nir
≤1
2≥
4O
Cef
ixim
e ≤
12
≥4
OC
efpo
doxi
me
≤2
4≥
8S
ee c
omm
ent (
6).
OC
efpr
ozil
≤8
16≥
32
Inv.
Cef
etam
et≤
48
≥16
Inv.
Cef
tibut
en≤
816
≥32
(11)
Ind
icat
ed fo
r urin
e is
olat
es o
nly.
CA
RB
APE
NEM
SB B B
Erta
pene
m
Imip
enem
or
mer
open
em
≤2
≤4
≤4
4 8 8
≥8
≥16
≥16
MO
NO
BA
CTA
MS
CA
ztre
onam
≤8
16≥
32S
ee c
omm
ent (
6).
AM
INO
GLY
CO
SID
ES(1
2) W
AR
NIN
G:F
or S
alm
onel
lasp
p. a
nd S
hige
llasp
p., a
min
ogly
cosi
des
may
appe
ar a
ctiv
e in
vitr
obu
t are
not
effe
ctiv
e cl
inic
ally,
and
isol
ates
sho
uld
not b
ere
porte
d as
sus
cept
ible
.A
Gen
tam
icin
≤4
8≥
16B
Am
ikac
in≤
1632
≥64
CK
anam
ycin
≤16
32≥
64C
Net
ilmic
in≤
816
≥32
CTo
bram
ycin
≤4
8≥
16TE
TRA
CYC
LIN
ESC
Tetra
cycl
ine
≤4
8≥
16(1
3)
Org
anis
ms
that
are
sus
cept
ible
to
tetra
cycl
ine
are
also
con
side
red
susc
eptib
le t
o do
xycy
clin
e an
d m
inoc
yclin
e.
How
ever
, so
me
orga
nism
s th
atar
e in
term
edia
te o
r res
ista
nt to
tetra
cycl
ine
may
be
susc
eptib
le to
dox
ycyc
line
or m
inoc
yclin
e or
bot
h.O
Dox
ycyc
line
≤4
8≥
16O
Min
ocyc
line
≤4
8≥
16
105
Tabl
e 2A
Ente
roba
cter
iace
aeM
7-M
IC
©Clinical and Laboratory Standards Institute. All rights reserved.
For Use With M7-A6–MIC Testing M100-S15
Tabl
e 2A
. (C
ontin
ued)
Test
/Rep
ort
Gro
upA
ntim
icro
bial
Age
ntM
IC (µµ
g/m
L)In
terp
retiv
e St
anda
rd
Com
men
ts
SI
RFL
UO
RO
QU
INO
LON
ES(1
4)
Fluo
roqu
inol
one-
susc
eptib
le s
train
s of
Sal
mon
ella
that
tes
t re
sist
ant
tona
lidix
ic a
cid
may
be
asso
ciat
ed w
ith c
linic
al f
ailu
re o
r de
laye
d re
spon
se in
fluor
oqui
nolo
ne-tr
eate
d pa
tient
s w
ith
extra
inte
stin
al
salm
onel
losi
s.E
xtra
inte
stin
al is
olat
es o
f Sa
lmon
ella
shou
ld a
lso
be t
este
d fo
r re
sist
ance
to
nalid
ixic
ac
id.
For
isol
ates
th
at
test
su
scep
tible
to
flu
oroq
uino
lone
s an
dre
sist
ant t
o na
lidix
ic a
cid,
the
phys
icia
n sh
ould
be
info
rmed
that
the
isol
ate
may
not
be
erad
icat
ed
by
fluor
oqui
nolo
ne
treat
men
t. A
cons
ulta
tion
with
an
infe
ctio
us d
isea
se p
ract
ition
er is
reco
mm
ende
d.B
Cip
roflo
xaci
n or
levo
floxa
cin
≤1
≤2
2 4≥
4≥
8U
Gat
iflox
acin
≤2
4≥
8B
Gem
iflox
acin
≤0.
250.
5≥
1(1
5) F
DA
appr
oved
for K
lebs
iella
pne
umon
iae
U U U
Lom
eflo
xaci
n or
norfl
oxac
in o
rof
loxa
cin
≤2
≤4
≤2
4 8 4
≥8
≥16
≥8
OE
noxa
cin
≤2
4≥
8O
Gre
paflo
xaci
n≤
1 2
≥4
Inv.
Fler
oxac
in≤
24
≥8
QU
INO
LON
ESU
Cin
oxac
in≤
1632
≥64
O
Nal
idix
ic a
cid
≤16
–≥
32S
ee c
omm
ent (
11).
(16)
In
addi
tion
to te
stin
g ur
ine
isol
ates
, nal
idix
ic a
cid
may
be
used
to te
st fo
rre
duce
d flu
oroq
uino
lone
su
scep
tibili
ty
in
isol
ates
fro
m
patie
nts
with
extra
inte
stin
al S
alm
onel
lain
fect
ions
. See
com
men
t (14
).FO
LATE
PAT
HW
AYIN
HIB
ITO
RS
BTr
imet
hopr
im-s
ulfa
met
hoxa
zole
≤2/
38–
≥4/
76U
Sul
fona
mid
es≤
256
–
≥51
2(1
7) S
ulfis
oxaz
ole
can
be u
sed
to re
pres
ent a
ny o
f the
cur
rent
ly a
vaila
ble
sulfo
nam
ide
prep
arat
ions
.U
Trim
etho
prim
≤8
–≥
16PH
ENIC
OLS
CC
hlor
amph
enic
ol≤
816
≥32
(18)
N
ot ro
utin
ely
repo
rted
agai
nst o
rgan
ism
s is
olat
ed fr
om th
e ur
inar
y tra
ct.
FOSF
OM
YCIN
SU
Fosf
omyc
in≤
6412
8≥
256
(19)
Fo
r use
with
E. c
olio
nly.
The
app
rove
d M
IC s
usce
ptib
ility
test
ing
met
hod
is a
gar d
ilutio
n. A
gar m
edia
sho
uld
be s
uppl
emen
ted
with
25
µg/m
Lof
glu
cose
-6-
phos
phat
e. B
roth
dilu
tion
shou
ld n
ot b
e pe
rform
ed.
NIT
RO
FUR
AN
TOIN
SU
Nitr
ofur
anto
in≤
3264
≥12
8
106
Tabl
e 2A
Ente
roba
cter
iace
aeM
7-M
IC
©Clinical and Laboratory Standards Institute. All rights reserved.
January 2005 Vol. 25 No. 1
Table 2A. (Continued)Screening and Confirmatory Tests for ESBLs in Klebsiella pneumoniae, K. oxytoca, Escherichiacoli, and Proteus mirabilis
a
Method Initial Screen Test Phenotypic Confirmatory TestMedium CAMHB CAMHBAntimicrobialConcentration
cefpodoxime 4 µg/mL orceftazidime 1 µg/mL oraztreonam 1 µg/mL orcefotaxime 1 µg/mL orceftriaxone 1 µg/mL
(The use of more than one antimicrobialagent for screening will improve thesensitivity of detection.)
ceftazidime 0.25-128 µg/mLceftazidime-clavulanic acid 0.25/4-128/4 µg/mLandcefotaxime 0.25-64 µg/mLcefotaxime-clavulanic acid 0.25/4-64/4 µg/mL
(Confirmatory testing requires use of bothcefotaxime and ceftazidime, alone and incombination with clavulanic acid.)
InoculumStandard broth dilution
recommendationsStandard broth dilution
recommendationsIncubationConditionsIncubation LengthResults Growth = may indicate ESBL
production (i.e., MIC ≥ 2 µg/mLfor ceftazidime, aztreonam, cefotaxime,or ceftriaxone; or MIC≥ 8 µg/mL for cefpodoxime)
A ≥ 3 twofold concentration decrease in an MIC foreither antimicrobial agent tested in combination withclavulanic acid versus its MIC when tested alone =ESBL (e.g., ceftazidime MIC= 8 µg/mL; ceftazidime-clavulanic acid MIC = 1 µg/mL).
QCRecommendations
When testing ESBL-screeningantimicrobial agents, K. pneumoniaeATCC® 700603 is provided for qualityassessment (e.g., training,competency or test evaluation).Either strain, K. pneumoniae ATCC®
700603 or E. coli ATCC® 25922, maythen be used for routine QC (e.g.,weekly or daily).
E. coli ATCC® 25922 = No growth(also refer to control limits listed in M7Table 3)
Klebsiella pneumoniae ATCC® 700603= Growth:
cefpodoxime MIC ≥ 8 µg/mLceftazidime MIC ≥ 2 µg/mLaztreonam MIC ≥ 2 µg/mLcefotaxime MIC ≥ 2 µg/mLceftriaxone MIC ≥ 2 µg/mL
When performing the ESBL confirmatory tests,K. pneumoniae ATCC® 700603 and E. coliATCC® 25922 should be tested routinely (e.g.,weekly or daily).
E. coli ATCC® 25922: <3 twofold concentrationdecrease in an MIC for an antimicrobial agenttested in combination with clavulanic acidversus its MIC when tested alone.
K. pneumoniae ATCC® 700603: ≥ 3 twofoldconcentration decrease in an MIC for anantimicrobial agent tested in combination withclavulanic acid versus its MIC when tested alone.
FOOTNOTE
a. Routine screening of Proteus mirabilis for ESBL production is not recommended. However, when it isdeemed clinically relevant (e.g., a bacteremic isolate) the ESBL screen testing MIC breakpoints, ceftazidime(MIC ≥≥ 2 µµg/mL), cefotaxime (MIC ≥≥ 2 µµg/mL ), or cefpodoxime (MIC ≥≥ 2 µµg/mL rather than ≥≥ 8 µµg/mL) willidentify presumptive ESBL production. The phenotypic confirmatory test using ceftazidime and cefotaximealone and in combination with clavulanic acid can confirm ESBL-producing strains. For all confirmed ESBL-producing P. mirabilis, the test interpretation should be reported as resistant for all penicillins,cephalosporins, and aztreonam.
107©Clinical and Laboratory Standards Institute. All rights reserved.
This page is intentionally left blank.
For Use With M7-A6–MIC Testing M100-S15
Tabl
e 2B
Non
-Ent
erob
acte
riace
aeM
7-M
IC
Gen
eral
Com
men
ts
(1)
Non
-Ent
erob
acte
riace
ae in
clud
e Ac
inet
obac
ter
spp.
, Ste
notro
phom
onas
mal
toph
ilia, P
seud
omon
assp
p., a
nd o
ther
non
fast
idio
us, g
luco
se-n
onfe
rmen
ting,
gram
-neg
ativ
e ba
cilli
. Ref
er to
Tab
le 2
K fo
r te
stin
g of
Bur
khol
deria
mal
lei a
nd B
. pse
udom
alle
i.
(2)
The
susc
eptib
ility
of P
. aer
ugin
osa
isol
ated
from
pat
ient
s w
ith c
ystic
fibr
osis
can
be
relia
bly
dete
rmin
ed b
y th
e re
fere
nce
agar
dilu
tion
or fr
ozen
ref
eren
cebr
oth
mic
rodi
lutio
n m
etho
ds, b
ut m
ay re
quire
ext
ende
d in
cuba
tion
up to
24
hour
s be
fore
repo
rting
as
susc
eptib
le.
(3)
P. a
erug
inos
am
ay d
evel
op r
esis
tanc
e du
ring
prol
onge
d th
erap
y w
ith a
ll an
tibio
tics.
The
refo
re, i
sola
tes
that
are
initi
ally
sus
cept
ible
may
bec
ome
resi
stan
tw
ithin
thre
e to
four
day
s af
ter i
nitia
tion
of th
erap
y. T
estin
g of
repe
at is
olat
es m
ay b
e w
arra
nted
.
(4)
Rx:
P. a
erug
inos
ain
fect
ions
in g
ranu
locy
tope
nic
patie
nts
and
serio
us in
fect
ions
in o
ther
pat
ient
s sh
ould
be
treat
ed w
ith m
axim
um d
oses
of t
he s
elec
ted
antip
seud
omon
al p
enic
illin
(car
boxy
peni
cilli
n or
ure
idop
enic
illin
) or c
efta
zidi
me
in c
ombi
natio
n w
ith a
n am
inog
lyco
side
.
NO
TE:
Info
rmat
ion
in b
oldf
ace
type
is c
onsi
dere
d te
ntat
ive
for o
ne y
ear.
©Clinical and Laboratory Standards Institute. All rights reserved.108
January 2005 Vol. 25 No. 1
Min
imal
QC
Rec
omm
enda
tions
(See
Tab
le 3
for A
ccep
tabl
e Q
C R
ange
s.)
Pseu
dom
onas
aer
ugin
osa
ATC
C®
2785
3Es
cher
ichi
a co
liAT
CC
®25
922
Esch
eric
hia
coli
ATC
C®
352
18 (f
or β
-lact
am/β
-lact
amas
e in
hibi
tor
com
bina
tions
)
Test
ing
Con
ditio
ns
Med
ium
:
Bro
th d
ilutio
n: C
atio
n-ad
just
ed M
uelle
r-H
into
n br
oth
(CA
MH
B)
Aga
r dilu
tion:
Mue
ller-
Hin
ton
agar
(MH
A)
Inoc
ulum
:G
row
th m
etho
d or
dire
ct c
olon
y su
spen
sion
, equ
ival
ent t
o a
0.5
McF
arla
nd s
tand
ard
Incu
batio
n:35
°C
±2
degr
ees;
am
bien
t air;
16
to 2
0 ho
urs
Test
/Rep
ort
Gro
upA
ntim
icro
bial
Age
ntM
IC (µµ
g/m
L)In
terp
retiv
e St
anda
rdC
omm
ents
SI
RPE
NIC
ILLI
NS
A A A
Mez
loci
llin
or
ticar
cilli
n
Pip
erac
illin
≤64
≤16
≤64
≤16
≤64
≤16
-32
-64
-32
-64
-32
-64
≥12
8≥
128
≥12
8≥
128
≥12
8≥
128
For P
. aer
ugin
osa
only
For a
ll ot
her n
on-E
nter
obac
teria
ceae
For P
. aer
ugin
osa
only
For a
ll ot
her n
on-E
nter
obac
teria
ceae
For P
. aer
ugin
osa
only
For a
ll ot
her n
on-E
nter
obac
teria
ceae
UC
arbe
nici
llin
≤12
8≤
1625
632
≥
512
≥64
For P
. aer
ugin
osa
only
For a
ll ot
her n
on-E
nter
obac
teria
ceae
OA
zloc
illin
≤64
- ≥
128
For P
. aer
ugin
osa
only
ββ -LA
CTA
M/ββ
-LA
CTA
MA
SE IN
HIB
ITO
R C
OM
BIN
ATIO
NS
BTi
carc
illin
-cla
vula
nic
acid
≤16
/232
/2-6
4/2
≥12
8/2
For n
on-E
nter
obac
teria
ceae
oth
er th
an P
. aer
ugin
osa
(5) M
ay b
e in
dica
ted
for p
rimar
y te
stin
g of
som
e Ps
eudo
mon
assp
p. (o
ther
than
P. a
erug
inos
a), S
. mal
toph
ilia, a
nd A
cine
toba
cter
spp.
OTi
carc
illin
-cla
vula
nic
acid
≤64
/2-
≥12
8/2
For P
. aer
ugin
osa
only
OA
mpi
cilli
n-su
lbac
tam
≤8/
416
/8≥
32/1
6(6
) M
ay b
e re
porte
d fo
r Aci
neto
bact
ersp
p. re
sist
ant t
o ot
her a
gent
sO
Pip
erac
illin
-tazo
bact
am≤
64/4
≤16
/4-
32/4
-64/
4≥
128/
4≥
128/
4Fo
r P. a
erug
inos
aon
lyFo
r all
othe
r non
-Ent
erob
acte
riace
ae
Tabl
e 2B
. M
IC In
terp
retiv
e St
anda
rds
(µµg/
mL)
for
Pseu
dom
onas
aer
ugin
osa
and
Oth
er N
on-E
nter
obac
teria
ceae
109
Tabl
e 2B
Non
-Ent
erob
acte
riace
aeM
7-M
IC
©Clinical and Laboratory Standards Institute. All rights reserved.
For Use With M7-A6–MIC Testing M100-S15
Tabl
e 2B
. (C
ontin
ued)
Test
/Rep
ort
Gro
upA
ntim
icro
bial
Age
ntM
IC (µµ
g/m
L)In
terp
retiv
e St
anda
rdC
omm
ents
SI
RC
EPH
EMS
(PA
REN
TER
AL)
(Inc
ludi
ng c
epha
losp
orin
s I,
II, II
I, an
d IV
. Ple
ase
refe
r to
Glo
ssar
y I.)
AC
efta
zidi
me
≤8
16≥
32B
Cef
epim
e≤
816
≥32
BC
efop
eraz
one
≤16
32≥
64C C
Cef
otax
ime
orce
ftria
xone
≤8
≤8
16-3
216
-32
≥64
≥64
UC
eftiz
oxim
e≤
816
-32
≥64
OM
oxal
acta
m≤
816
-32
≥64
(7)
May
be
indi
cate
d fo
r prim
ary
test
ing
of S
. mal
toph
ilia.
CA
RB
APE
NEM
SB
Imip
enem
≤4
8≥
16B
Mer
open
em≤
48
≥16
LIPO
PEPT
IDES
CPo
lym
yxin
B≤≤
2-
≥≥4
(8)
Poly
myx
in B
MIC
res
ult c
an p
redi
ct c
olis
tin M
IC.
MO
NO
BA
CTA
MS
BA
ztre
onam
≤8
16≥
32A
MIN
OG
LYC
OSI
DES
AG
enta
mic
in≤
48
≥16
BA
mik
acin
≤16
32≥
64B
Tobr
amyc
in≤
48
≥16
CN
etilm
icin
≤8
16≥
32TE
TRA
CYC
LIN
ES(9
) O
rgan
ism
s th
at a
re s
usce
ptib
le t
o te
tracy
clin
e ar
e al
so c
onsi
dere
d su
scep
tible
to
doxy
cycl
ine
and
min
ocyc
line.
How
ever
, som
e or
gani
sms
that
are
inte
rmed
iate
or r
esis
tant
tote
tracy
clin
e m
ay b
e su
scep
tible
to d
oxyc
yclin
e or
min
ocyc
line
or b
oth.
UTe
tracy
clin
e≤
48
≥16
See
com
men
t (5)
.O
Dox
ycyc
line
≤4
8≥
16O
Min
ocyc
line
≤4
8≥
16FL
UO
RO
QU
INO
LON
ESB B
Cip
roflo
xaci
nLe
voflo
xaci
n ≤
1≤
22 4
≥4
≥8
U U U
Lom
eflo
xaci
n or
of
loxa
cin
orno
rflox
acin
≤2
≤2
≤4
4 4 8
≥8
≥8
≥16
OG
atifl
oxac
in≤
24
≥8
(10)
Thi
s br
eakp
oint
app
lies
to is
olat
es fr
om th
e ur
inar
y tra
ct o
nly.
FOLA
TE P
ATH
WAY
INH
IBIT
OR
SB
Trim
etho
prim
-sul
fam
etho
xazo
le≤
2/38
-≥
4/76
See
com
men
t (5)
.U
Sul
fona
mid
es≤
256
-≥
512
(11)
Sul
fisox
azol
e ca
n be
use
d to
repr
esen
t any
of t
he c
urre
ntly
ava
ilabl
e su
lfona
mid
epr
epar
atio
ns.
PHEN
ICO
LSC
Chl
oram
phen
icol
≤8
16≥
32(1
2) N
ot ro
utin
ely
repo
rted
on is
olat
es fr
om th
e ur
inar
y tra
ct.
See
com
men
t (5)
.
110
Tabl
e 2C
Stap
hylo
cocc
ussp
p.M
7-M
IC
©Clinical and Laboratory Standards Institute. All rights reserved.
January 2005 Vol. 25 No. 1Ta
ble
2C.
MIC
Inte
rpre
tive
Stan
dard
s (µµ
g/m
L) fo
rSt
aphy
loco
ccus
spp.
Min
imal
QC
Rec
omm
enda
tions
(S
ee T
able
3 f
or a
ccep
tabl
e Q
Cra
nges
.)
Stap
hylo
cocc
us a
ureu
sAT
CC
® 2
9213
Esch
eric
hia
coli
ATC
C®
3521
8 (F
or β
-lact
am/β
-lact
amas
e in
hibi
tor
com
bina
tions
)
Stap
hylo
cocc
us a
ureu
sAT
CC
® B
AA
-977
and
Sta
phyl
ococ
cus
aure
usAT
CC
®
BA
A-9
76
(for
qu
ality
as
sess
men
t of
th
ecl
inda
myc
in in
duct
ion
test
)
Test
ing
Con
ditio
ns
Med
ium
:B
roth
dilu
tion:
Cat
ion-
adju
sted
Mue
ller-
Hin
ton
brot
h (C
AM
HB
) C
AM
HB
plu
s 2%
NaC
l for
oxa
cilli
n, m
ethi
cilli
n, a
nd n
afci
llin;
CA
MH
B
supp
lem
ente
d to
50
µµ g/m
Lca
lciu
m fo
r da
ptom
ycin
A
gar d
ilutio
n: M
uelle
r-H
into
n ag
ar (M
HA
); A
gar
dilu
tion
is
curr
ently
not
rec
omm
ende
d fo
r da
ptom
ycin
. M
HA
plus
2%
NaC
l for
oxa
cilli
n, m
ethi
cilli
n, a
nd n
afci
llin
Inoc
ulum
:D
irect
col
ony
susp
ensi
on, e
quiv
alen
t to
a 0.
5 M
cFar
land
sta
ndar
dIn
cuba
tion:
33 to
35
°C (d
o no
t exc
eed
35 °
C);
ambi
ent a
ir; 1
6 to
20
hour
s; 2
4 ho
urs
for o
xaci
llin,
met
hici
llin,
naf
cilli
n, a
nd v
anco
myc
in Gen
eral
Com
men
ts
(1)
His
toric
ally,
resi
stan
ce to
the
peni
cilli
nase
-sta
ble
peni
cilli
ns (s
ee G
loss
ary
I) h
as b
een
refe
rred
to a
s “m
ethi
cilli
n re
sist
ance
,” th
us th
e ac
rony
ms
MR
SA
(for “
met
hici
llin-
resi
stan
t S. a
ureu
s”) o
r MR
S (f
or “m
ethi
cilli
n-re
sist
ant s
taph
yloc
occi
”) a
re s
till c
omm
only
use
d ev
en th
ough
met
hici
llin
is n
o lo
nger
the
agen
t of c
hoic
e fo
r tes
ting
ortre
atm
ent.
In th
is d
ocum
ent,
resi
stan
ce to
thes
e ag
ents
may
be
refe
rred
to u
sing
sev
eral
term
s (e
.g.,
“MR
S,”
“met
hici
llin
resi
stan
ce,”
“oxa
cilli
n re
sist
ance
”).
(2)
For
oxac
illin
-sus
cept
ible
Sta
phyl
ococ
cus
aure
usan
d co
agul
ase-
nega
tive
stap
hylo
cocc
i, re
sults
for
par
ente
ral a
nd o
ral c
ephe
ms,
ββ-la
ctam
/ββ-la
ctam
ase
inhi
bito
r com
bina
tions
, and
car
bape
nem
s, if
test
ed, s
houl
d be
repo
rted
acc
ordi
ng to
the
resu
lts g
ener
ated
usi
ng ro
utin
e in
terp
retiv
e cr
iteria
. See
com
men
t(3
) for
rep
ortin
g ββ -
lact
am r
esul
ts o
n ox
acill
in-r
esis
tant
str
ains
.
(3)
WA
RN
ING
:For
oxa
cilli
n-re
sist
ant S
. aur
eus
and
coag
ulas
e-ne
gativ
e st
aphy
loco
cci (
MR
S),
othe
r ββ -
lact
am a
gent
s, i.
e., p
enic
illin
s, ββ
-lact
am/ββ
-lact
amas
e in
hibi
tor
com
bina
tions
, cep
hem
s, a
nd c
arba
pene
ms
may
app
ear a
ctiv
e in
vitr
o bu
t are
not
effe
ctiv
e cl
inic
ally.
Res
ults
for t
hese
dru
gs s
houl
d be
repo
rted
as re
sist
ant o
r sho
uld
not b
e re
porte
d. T
his
is b
ecau
se m
ost c
ases
of d
ocum
ente
d M
RS
infe
ctio
ns h
ave
resp
onde
d po
orly
to β
-lact
am th
erap
y, o
r bec
ause
con
vinc
ing
clin
ical
dat
a ha
ve y
etto
be
pres
ente
d th
at d
ocum
ent c
linic
al e
ffica
cy fo
r tho
se a
gent
s.
(4)
Det
ectio
n of
oxa
cilli
n re
sist
ance
: Tes
ts fo
r m
ecA
or fo
r th
e pr
otei
n ex
pres
sed
by m
ecA
, the
pen
icill
in-b
indi
ng p
rote
in 2
a (P
BP
2a, a
lso
calle
d PB
P2')
are
the
mos
t ac
cura
te m
etho
ds f
or p
redi
ctio
n of
res
ista
nce
to o
xaci
llin
and
coul
d be
use
d to
con
firm
res
ults
for
isol
ates
of
sta
phyl
ococ
ci
from
ser
ious
infe
ctio
ns. I
sola
tes
of s
taph
yloc
occi
tha
t ar
e sh
own
to c
arry
the
mec
Age
ne, o
r th
at p
rodu
ce P
BP
2a, t
he m
ecA
gene
pro
duct
, sho
uld
be r
epor
ted
asox
acill
in r
esis
tant
. Iso
late
s th
at a
re n
ot s
how
n to
car
ry m
ecA
or d
o no
t pro
duce
PB
P2a
sho
uld
be r
epor
ted
as o
xaci
llin
susc
eptib
le if
oxa
cilli
n M
ICS
are
≤≤ 2
µµ g/m
L. B
ecau
se o
f the
rar
e oc
curr
ence
of r
esis
tanc
e m
echa
nism
s ot
her
than
mec
A, i
sola
tes
that
are
neg
ativ
e fo
r th
e m
ecA
gene
or
do n
ot p
rodu
cePB
P2a
, but
for
whi
ch M
ICs
are
≥≥4
µµ g/m
Lsh
ould
be
repo
rted
as
oxac
illin
res
ista
nt.
(5)
Rou
tine
test
ing
of u
rine
isol
ates
of S
. sap
roph
ytic
us is
not
adv
ised
, bec
ause
infe
ctio
ns re
spon
d to
con
cent
ratio
ns a
chie
ved
in u
rine
of a
ntim
icro
bial
age
nts
com
mon
lyus
ed to
trea
t acu
te, u
ncom
plic
ated
urin
ary
tract
infe
ctio
ns (e
.g.,
nitro
fura
ntoi
n, tr
imet
hopr
im ±
sul
fam
etho
xazo
le, o
r a fl
uoro
quin
olon
e).
(6)
For s
ome
orga
nism
/ant
imic
robi
al a
gent
com
bina
tions
, the
abs
ence
of r
esis
tant
stra
ins
prec
lude
s de
finin
g an
y re
sults
cat
egor
ies
othe
r tha
n “s
usce
ptib
le.”
For
stra
ins
yiel
ding
resu
lts s
ugge
stiv
e of
a “n
onsu
scep
tible
” cat
egor
y, o
rgan
ism
iden
tific
atio
n an
d an
timic
robi
al s
usce
ptib
ility
test
resu
lts s
houl
d be
con
firm
ed. S
ubse
quen
tly, t
heis
olat
es s
houl
d be
sav
ed a
nd s
ubm
itted
to a
refe
renc
e la
bora
tory
that
will
con
firm
resu
lts u
sing
a C
LSI/N
CC
LS re
fere
nce
dilu
tion
met
hod.
NO
TE:
Info
rmat
ion
in b
oldf
ace
type
is c
onsi
dere
d te
ntat
ive
for o
ne y
ear.
111©Clinical and Laboratory Standards Institute. All rights reserved.
Tabl
e 2C
. (C
ontin
ued)
For Use With M7-A6–MIC Testing M100-S15
Test
/Rep
ort
Gro
upA
ntim
icro
bial
Age
ntM
IC (µµ
g/m
L)In
terp
retiv
e St
anda
rdC
omm
ents
SI
RPE
NIC
ILLI
NS
(7)
Pen
icill
in-s
usce
ptib
le s
taph
yloc
occi
are
als
o su
scep
tible
to
othe
r pe
nici
llins
, β-
lact
am/β
-lact
amas
ein
hibi
tor
com
bina
tions
, ce
phem
s, a
nd c
arba
pene
ms
appr
oved
for
use
by
the
FDA
for
stap
hylo
cocc
alin
fect
ions
. Pen
icill
in-r
esis
tant
, oxa
cilli
n-su
scep
tible
stra
ins
are
resi
stan
t to
peni
cilli
nase
-labi
le p
enic
illin
s bu
tsu
scep
tible
to
othe
r pe
nici
llina
se-s
tabl
e pe
nici
llins
, β-
lact
am/β
-lact
amas
e in
hibi
tor
com
bina
tions
, re
leva
ntce
phem
s, a
nd c
arba
pene
ms.
Oxa
cilli
n-re
sist
ant s
taph
yloc
occi
are
resi
stan
t to
all c
urre
ntly
ava
ilabl
e β-
lact
aman
tibio
tics.
Thu
s, s
usce
ptib
ility
or
resi
stan
ce to
a w
ide
arra
y of
β-la
ctam
ant
ibio
tics
may
be
dedu
ced
from
test
ing
only
pen
icill
in a
nd o
xaci
llin.
Rou
tine
test
ing
of o
ther
pen
icill
ins,
β-la
ctam
/β-la
ctam
ase
inhi
bito
rco
mbi
natio
ns, c
ephe
ms,
and
car
bape
nem
s is
not
adv
ised
.
See
com
men
t (3)
. A
Pen
icill
in
≤0.
12-
≥0.
25(8
) R
esis
tant
stra
ins
of S
. aur
eus
prod
uce
beta
-lact
amas
e, a
nd th
e te
stin
g of
pen
icilli
n in
stea
d of
am
pici
llinis
pre
ferre
d. P
enic
illin
shou
ld b
e us
ed to
test
the
susc
eptib
ility
of a
ll st
aphy
loco
cci t
o al
l pen
icilli
nase
-labi
lepe
nici
llins,
suc
h as
am
pici
llin,
amox
icilli
n, a
zloc
illin,
car
beni
cillin
, m
ezlo
cillin
, pi
pera
cillin
, an
d tic
arci
llin. A
peni
cillin
MIC
of ≤
0.03
µg/
mL
usua
lly im
plie
s la
ck o
f β-la
ctam
ase
prod
uctio
n, a
nd M
ICs
of ≥
0.25
µg/
mL
shou
ld b
e co
nsid
ered
resi
stan
t; st
aphy
loco
cci w
ith p
enic
illin
MIC
s be
twee
n 0.
06 to
0.1
2 µg
/mL
may
or m
ayno
t pro
duce
β-la
ctam
ase,
and
an
indu
ced
beta
-lact
amas
e te
st c
an c
larif
y th
ese
MIC
s (s
ee M
7-A6
, Sec
tion
10.2
). A
posi
tive
β-la
ctam
ase
test
pre
dict
s re
sist
ance
to
peni
cillin
, am
pici
llin,
amox
icilli
n, c
arbe
nici
llin,
ticar
cillin
, m
ezlo
cillin
, an
d pi
pera
cillin
. Fo
r ox
acilli
n-re
sist
ant
stap
hylo
cocc
i, re
port
as r
esis
tant
or
do n
otre
port.
AO
xaci
llin
≤2
≤0.
25- -
≥4
≥0.
5Fo
r S. a
ureu
san
d S.
lugd
unen
sis.
For c
oagu
lase
-neg
ativ
e st
aphy
loco
cci,
exce
pt S
. lug
dune
nsis
.
(9)
Of t
he p
enic
illin
ase-
stab
le p
enic
illin
s, o
xaci
llin
may
be
test
ed, a
nd r
esul
ts c
an b
e ap
plie
d to
the
othe
rpe
nici
llina
se-s
tabl
e pe
nici
llins
, cl
oxac
illin
, di
clox
acill
in a
nd f
lucl
oxac
illin
. Te
stin
g of
oxa
cilli
n is
pre
ferr
ed,
sinc
e it
is m
ore
resi
stan
t to
degr
adat
ion
in s
tora
ge, a
nd b
ecau
se it
is m
ore
likel
y to
det
ect h
eter
ores
ista
ntst
rain
s. (S
ee th
e ta
ble
at th
e en
d of
this
tabl
e fo
r the
oxa
cilli
n ag
ar s
cree
n te
st fo
r S. a
ureu
s.)
(10)
Int
erpr
etiv
e cr
iteria
for c
oagu
lase
-neg
ativ
e st
aphy
loco
cci c
orre
late
with
the
pres
ence
or a
bsen
ce o
f the
gene
enc
odin
g m
ethi
cilli
n re
sist
ance
(m
ecA
) fo
r S.
epi
derm
idis
.Th
ese
inte
rpre
tive
crite
ria m
ay o
verc
all
resi
stan
ce fo
r ot
her
coag
ulas
e-ne
gativ
e st
aphy
loco
cci (
e.g.
, S. s
apro
phyt
icus
). Fo
r se
rious
infe
ctio
ns w
ithco
agul
ase-
nega
tive
stap
hylo
cocc
i oth
er th
an S
. epi
derm
idis
,tes
ting
for
mec
Aor
the
prot
ein
expr
esse
d by
mec
A, t
he p
enic
illin
bin
ding
pro
tein
2a
(PB
P2a
, “al
so k
now
n as
” PB
P2'
) may
be
appr
opria
te fo
r stra
ins
for
whi
ch th
e ox
acill
in M
ICs
are
0.5
to 2
µg/
mL.
(11)
The
resu
lts o
f dis
k di
ffusi
on te
sts
usin
g a
30-µ
g ce
foxi
tin d
isk
and
alte
rnat
e br
eakp
oint
s (s
ee b
ox a
t the
end
of t
his
tabl
e) c
an b
e us
ed t
o pr
edic
t m
ecA-
med
iate
d re
sist
ance
in s
taph
yloc
occi
. C
ompa
red
to M
ICte
sts,
the
cefo
xitin
dis
k te
st is
equ
ival
ent i
n se
nsiti
vity
and
spe
cific
ity fo
r S.
aur
eus.
For
coag
ulas
e-ne
gativ
e st
aphy
loco
cci,
the
cefo
xitin
dis
k te
st,
whe
n co
mpa
red
to o
xaci
llin
MIC
tes
ts,
has
equa
lse
nsiti
vity
but
hig
her
spec
ifici
ty (i
.e.,
the
cefo
xitin
dis
k te
st is
mor
e ac
cura
te th
an th
e ox
acill
in M
ICte
st fo
r ide
ntify
ing
oxac
illin
-sus
cept
ible
str
ains
).
OA
mpi
cilli
n≤
0.25
-
≥0.
5(1
2) C
lass
repr
esen
tativ
e fo
r am
pici
llin
and
amox
icill
in.
(13)
For
oxa
cilli
n-re
sist
ant s
taph
yloc
occi
, rep
ort a
s re
sist
ant o
r do
not r
epor
t.O
Met
hici
llin
≤8
-≥
16
(14)
For
use
with
S. a
ureu
son
ly.
ON
afci
llin
≤2
-≥
4(1
5) F
or u
se w
ith S
. aur
eus
only.
Tabl
e 2C
Stap
hylo
cocc
ussp
p.M
7-M
IC
112
Tabl
e 2C
Stap
hylo
cocc
ussp
p.M
7-M
IC
©Clinical and Laboratory Standards Institute. All rights reserved.
January 2005 Vol. 25 No. 1
Tabl
e 2C
. (C
ontin
ued)
Test
/Rep
ort
Gro
upA
ntim
icro
bial
Age
ntM
IC (µµ
g/m
L)In
terp
retiv
e St
anda
rdC
omm
ents
SI
Rββ -
LAC
TAM
/ββ-L
AC
TAM
ASE
INH
IBIT
OR
CO
MB
INAT
ION
S(1
6) F
or o
xaci
llin-
resi
stan
t sta
phyl
ococ
ci, r
epor
t as
resi
stan
t or d
o no
t rep
ort.
OA
mox
icill
in-c
lavu
lani
c ac
id≤
4/2
- ≥
8/4
OA
mpi
cilli
n-su
lbac
tam
≤8/
416
/8≥
32/1
6 O
Pip
erac
illin
-tazo
bact
am≤
8/4
-≥
16/4
OTi
carc
illin
-cla
vula
nic
acid
≤8/
2-
≥16
/2C
EPH
EMS
(PA
REN
TER
AL)
(Inc
ludi
ng c
epha
losp
orin
s I,
II, II
I, an
d IV
. S
ee c
omm
ent (
7).
Plea
se r
efer
to G
loss
ary
I.)(1
7) F
or o
xaci
llin-
resi
stan
t sta
phyl
ococ
ci, r
epor
t as
resi
stan
t or d
o no
t rep
ort.
OC
efam
ando
le≤
816
≥32
OC
efaz
olin
≤8
16≥
32O
Cef
epim
e≤
816
≥32
OC
efm
etaz
ole
≤16
32≥
64O
Cef
onic
id≤
816
≥32
OC
efop
eraz
one
≤16
32≥
64O
Cef
otax
ime
≤8
16-3
2≥
64O
Cef
otet
an≤
1632
≥64
OC
efox
itin
≤8
16≥
32S
ee c
omm
ent (
11)
OC
efta
zidi
me
≤8
16≥
32O
Cef
tizox
ime
≤8
16-3
2≥
64O
Cef
triax
one
≤8
16-3
2≥
64O
Cef
urox
ime
sodi
um (p
aren
tera
l)≤
816
≥32
OC
epha
loth
in≤
816
≥32
OM
oxal
acta
m≤
816
-32
≥64
CEP
HEM
S (O
RA
L)(1
8) F
or o
xaci
llin-
resi
stan
t sta
phyl
ococ
ci, r
epor
t as
resi
stan
t or d
o no
t rep
ort.
OC
efac
lor
≤8
16≥
32O
Cef
dini
r ≤
12
≥4
OC
efpo
doxi
me
≤2
4≥
8O
Cef
proz
il ≤
816
≥32
OC
efur
oxim
e ax
etil
(ora
l)≤
48-
16≥
32O
Lora
carb
ef
≤8
16≥
32C
AR
BA
PEN
EMS
See
com
men
t (7)
.(1
9) F
or o
xaci
llin-
resi
stan
t sta
phyl
ococ
ci, r
epor
t as
resi
stan
t or d
o no
t rep
ort.
OE
rtape
nem
≤2
4≥
8O
Imip
enem
≤4
8≥
16O
Mer
open
em≤
48
≥16
113
Tabl
e 2C
Stap
hylo
cocc
ussp
p.M
7-M
IC
©Clinical and Laboratory Standards Institute. All rights reserved.
For Use With M7-A6–MIC Testing M100-S15Ta
ble
2C. (
Con
tinue
d)Te
st/R
epor
tG
roup
Ant
imic
robi
al A
gent
MIC
(µµg/
mL)
Inte
rpre
tive
Stan
dard
Com
men
ts
SI
RG
LYC
OPE
PTID
ESB
Vanc
omyc
in≤
48-
16≥
32(2
0) V
anco
myc
in-r
esis
tant
S.
aure
us(V
RSA
) st
rain
s (M
ICs
≥32
µg/m
L) a
rere
liabl
y de
tect
ed b
y th
e br
oth
mic
rodi
lutio
n re
fere
nce
met
hod.
Whe
n us
ing
othe
rM
IC m
etho
ds th
at h
ave
not b
een
valid
ated
to d
etec
t VR
SA, B
HI v
anco
myc
in a
gar
scre
en p
late
s co
ntai
ning
6 µµ
g/m
Lof
van
com
ycin
, su
ch a
s th
ose
used
for
dete
ctio
n of
van
com
ycin
-res
ista
nt e
nter
ococ
ci (
see
M7-
Tabl
e 2D
), sh
ould
be
inoc
ulat
ed to
enh
ance
the
sens
itivi
ty o
f det
ectin
g va
ncom
ycin
-res
ista
nt s
trai
ns.
(21)
S
end
any
stap
hylo
cocc
i det
erm
ined
to
have
an
elev
ated
MIC
for
van
com
ycin
(MIC
≥4
µg/m
L) to
a re
fere
nce
labo
rato
ry.
Inv.
Teic
opla
nin
≤8
16≥
32LI
POPE
PTID
ESB
Dap
tom
ycin
≤≤1
--
See
com
men
t (6)
.A
MIN
OG
LYC
OSI
DES
CG
enta
mic
in≤
48
≥16
OA
mik
acin
≤16
32≥
64O
Kan
amyc
in≤
1632
≥64
ON
etilm
icin
≤8
16≥
32O
Tobr
amyc
in≤
48
≥16
MA
CR
OLI
DES
B B B
Azi
thro
myc
in o
rcl
arith
rom
ycin
or
eryt
hrom
ycin
≤2
≤2
≤0.
5
4 4 1-4
≥8
≥8
≥8
(22)
N
ot r
outin
ely
test
ed a
nd r
epor
ted
agai
nst
orga
nism
s is
olat
ed f
rom
the
urin
ary
tract
.
OD
irith
rom
ycin
≤2
4≥
8K
ETO
LID
ESB
Telit
hrom
ycin
≤1
2≥
4
TETR
AC
YCLI
NES
CTe
tracy
clin
e≤
48
≥16
(23)
Org
anis
ms
that
are
sus
cept
ible
to te
tracy
clin
e ar
e al
so c
onsi
dere
d su
scep
tible
todo
xycy
clin
e an
d m
inoc
yclin
e.
How
ever
, so
me
orga
nism
s th
at a
re i
nter
med
iate
or
resi
stan
t to
tetra
cycl
ine
may
be
susc
eptib
le to
dox
ycyc
line
or m
inoc
yclin
e or
bot
h.O
Dox
ycyc
line
≤4
8≥
16O
Min
ocyc
line
≤4
8≥
16FL
UO
RO
QU
INO
LON
ES(2
4)
Stap
hylo
cocc
us s
pp.
may
dev
elop
res
ista
nce
durin
g pr
olon
ged
ther
apy
with
quin
olon
es. T
here
fore
, iso
late
s th
at a
re in
itial
ly s
usce
ptib
le m
ay b
ecom
e re
sist
ant w
ithin
thre
e to
four
day
s af
ter i
nitia
tion
of th
erap
y. T
estin
g of
repe
at is
olat
es m
ay b
e w
arra
nted
.C C C C C
Cip
roflo
xaci
n or
levo
floxa
cin
orof
loxa
cin
Gat
iflox
acin
or
mox
iflox
acin
≤1
≤≤1
≤≤1
≤≤0.
5≤≤
0.5
2 2 2 1 1
≥4
≥≥4
≥≥4
≥≥2
≥≥2
U ULo
mef
loxa
cin
orno
rflox
acin
≤2
≤4
4 8≥
8≥
16
114
Tabl
e 2C
Stap
hylo
cocc
ussp
p.M
7-M
IC
©Clinical and Laboratory Standards Institute. All rights reserved.
January 2005 Vol. 25 No. 1
Tabl
e 2C
. (C
ontin
ued)
Test
/Rep
ort
Gro
upA
ntim
icro
bial
Age
ntM
IC (µµ
g/m
L)In
terp
retiv
e St
anda
rd
Com
men
ts
SI
RFL
UO
RO
QU
INO
LON
ES (C
ontin
ued)
OE
noxa
cin
≤2
4≥
8(2
5) F
DA
appr
oved
for S
. sap
roph
ytic
usan
d S.
epi
derm
idis
(not
S. a
ureu
s).
OG
repa
floxa
cin
≤1
2 ≥
4O
Spar
floxa
cin
≤0.
51
≥2
Inv.
Fler
oxac
in≤
24
≥8
NIT
RO
FUR
AN
TOIN
SU
Nitr
ofur
anto
in≤
3264
≥12
8LI
NC
OSA
MID
ESB
C
linda
myc
in
≤0.
51-
2≥
4(2
6) M
acro
lide-
resi
stan
t iso
late
s of
S. a
ureu
s an
d co
agul
ase-
nega
tive
Stap
hylo
cocc
ussp
p.m
ay h
ave
cons
titut
ive
or in
duci
ble
resi
stan
ce to
clin
dam
ycin
[met
hyla
tion
of th
e 23
S rR
NA
enco
ded
by t
he e
rmge
ne a
lso
refe
rred
to
as M
LSB
(mac
rolid
e, li
ncos
omid
e, a
nd t
ype
Bst
rept
ogra
min
) re
sist
ance
] or
may
be
resi
stan
t on
ly t
o m
acro
lides
(ef
flux-
mec
hani
smen
code
d by
the
msr
Age
ne).
Indu
cibl
e cl
inda
myc
in r
esis
tanc
e ca
n be
det
ecte
d us
ing
adi
sk a
ppro
xim
atio
n te
st b
y pl
acin
g a
2-µg
clin
dam
ycin
dis
k 15
mm
aw
ay fr
om th
e ed
ge o
fa
15-µ
g er
ythr
omyc
in d
isk
on a
sta
ndar
d bl
ood
agar
pla
te u
sed
for
the
inoc
ulum
pur
itych
eck.
Fol
low
ing
incu
batio
n, o
rgan
ism
s th
at d
o no
t sho
w fl
atte
ning
of t
he c
linda
myc
in z
one
shou
ld b
e re
porte
d as
clin
dam
ycin
sus
cept
ible
. O
rgan
ism
s th
at s
how
fla
tteni
ng o
f th
ecl
inda
myc
in z
one
adja
cent
to
the
eryt
hrom
ycin
dis
k (r
efer
red
to a
s a
“D”
zone
) ha
vein
duci
ble
clin
dam
ycin
resi
stan
ce. S
uch
isol
ates
sho
uld
be re
porte
d as
clin
dam
ycin
resi
stan
t.A
com
men
t tha
t "Th
is is
olat
e is
pre
sum
ed to
be
resi
stan
t bas
ed o
n de
tect
ion
of in
duci
ble
clin
dam
ycin
res
ista
nce.
Clin
dam
ycin
may
stil
l be
effe
ctiv
e in
som
e pa
tient
s."
may
be
incl
uded
. For
qua
lity
cont
rol/q
ualit
y as
sess
men
t rec
omm
enda
tions
, ref
er to
Tab
le 3
of
M2.
See
com
men
t (22
).
FOLA
TE P
ATH
WAY
INH
IBIT
OR
SB
Tr
imet
hopr
im-s
ulfa
met
hoxa
zole
≤2/
38-
≥4/
76U
Sul
fona
mid
es≤
256
-≥
512
(27)
S
ulfis
oxaz
ole
can
be u
sed
to r
epre
sent
any
of
the
curr
ently
ava
ilabl
e su
lfona
mid
epr
epar
atio
ns.
UTr
imet
hopr
im≤
8-
≥16
PHEN
ICO
LSC
Chl
oram
phen
icol
≤8
16≥
32S
ee c
omm
ent (
22).
AN
SAM
YCIN
SC
Rifa
mpi
n≤
12
≥4
(28)
Rx:
Rifa
mpi
n sh
ould
not
be
used
alo
ne fo
r che
mot
hera
py.
STR
EPTO
GR
AM
INS
CQ
uinu
pris
tin-d
alfo
pris
tin≤
12
≥4
OXA
ZOLI
DIN
ON
ESB
Line
zolid
≤4
--
See
com
men
t (6)
.
For Use With M7-A6–MIC Testing M100-S15
©Clinical and Laboratory Standards Institute. All rights reserved. 115
Disk Diffusion Testa for Prediction of mecA-mediated Resistance in StaphylococciAntimicrobial
Agent(Disk Content)
Organism Group Zone Diameter,Nearest Whole mm
Comments
Cefoxitin (30 µg) S. aureus and S.lugdunensis
≤ 19 ≥ 20 (29) S. aureus for whichcefoxitin disk diffusion zonesare ≤ 19 mm should bereported as oxacillin resistant.Those for which cefoxitin zonesare ≥ 20 mm should be reportedas oxacillin susceptible.
Coagulase-negativestaphylococci exceptS. lugdunensis
≤ 24 ≥ 25 (30) Coagulase-negativestaphylococci for which cefoxitindisk diffusion zones are ≤ 24mm should be reported asoxacillin resistant. Those forwhich cefoxitin zones are ≥ 25mm should be reported asoxacillin susceptible.
a Use standard disk diffusion testing conditions and incubate for 24 hours; however, results may be reported after18 hours incubation if resistant. Read the cefoxitin disk test using reflected light.
Table 2C. (Continued)
Tabl
e 2C
Stap
hylo
cocc
ussp
p.M
7-M
IC
Oxacillin-Salt Agar Screening Test for Staphylococcus aureus
Screen Test Oxacillin Resistance
Medium MHA with NaCl (4% w/v; 0.68 mol/L)Antimicrobial concentration 6 µg/mL oxacillin
Inoculum Direct colony suspension to obtain 0.5 McFarland turbidityUsing a 1-µL loop that was dipped in the suspension, spot an area 10 to 15mm in diameter. Alternatively, using a swab dipped in the suspension andexpressed, spot a similar area or streak an entire quadrant.
Incubation conditionsIncubation length
35 °C; ambient air 24 hours
Results >1 colony = resistantExamine carefully with transmitted light for >1 colony or light film of growth.
QC Recommendations Staphylococcus aureus ATCC® 29213 - Susceptible Staphylococcus aureus ATCC® 43300 - Resistant
Test
ing
Con
ditio
ns
Med
ium
:B
roth
dilu
tion:
Cat
ion-
adju
sted
Mue
ller-
Hin
ton
brot
h (C
AM
HB
); C
AM
HB
sup
plem
ente
d to
50
µµ g/m
Lca
lciu
m fo
rda
ptom
ycin
Aga
r dilu
tion:
Mue
ller-
Hin
ton
agar
(MH
A);
Aga
r di
lutio
n is
cu
rren
tly n
ot r
ecom
men
ded
for
dapt
omyc
in
Inoc
ulum
:G
row
th m
etho
d or
dire
ct c
olon
y su
spen
sion
, equ
ival
ent t
o a
0.5
McF
arla
nd s
tand
ard
Incu
batio
n:35
°C
±2
degr
ees;
am
bien
t air;
16
to 2
0 ho
urs;
24
hour
s fo
r va
ncom
ycin
January 2005 Vol. 25 No. 1
116
Tabl
e 2D
Ente
roco
ccus
spp.
M7-
MIC
©Clinical and Laboratory Standards Institute. All rights reserved.
Tabl
e 2D
. M
IC In
terp
retiv
e St
anda
rds
(µµg/
mL)
for
Ente
roco
ccus
spp.
Min
imal
QC
Rec
omm
enda
tions
(See
Tab
le 3
for A
ccep
tabl
e Q
CR
ange
s.)
Ente
roco
ccus
faec
alis
ATC
C®
2921
2
Gen
eral
Com
men
ts
(1)
WA
RN
ING
:
For
Ente
roco
ccus
sp
p.,
ceph
alos
porin
s,
amin
ogly
cosi
des
(exc
ept
for
high
-leve
l re
sist
ance
sc
reen
ing)
, cl
inda
myc
in,
and
trim
etho
prim
-su
lfam
etho
xazo
le m
ay a
ppea
r act
ive
in v
itro
but a
re n
ot e
ffect
ive
clin
ical
ly, a
nd is
olat
es s
houl
d no
t be
repo
rted
as s
usce
ptib
le.
(2)
Syn
ergy
bet
wee
n am
pici
llin,
pen
icill
in, o
r van
com
ycin
and
an
amin
ogly
cosi
de c
an b
e pr
edic
ted
for e
nter
ococ
ci b
y us
ing
a hi
gh-le
vel a
min
ogly
cosi
de (g
enta
mic
inan
d st
rept
omyc
in)
scre
enin
g te
st. O
ther
am
inog
lyco
side
s ne
ed n
ot b
e te
sted
, bec
ause
thei
r ac
tiviti
es a
gain
st e
nter
ococ
ci a
re n
ot s
uper
ior
to g
enta
mic
in a
ndst
rept
omyc
in.
(3)
Bec
ause
of l
imite
d al
tern
ativ
es, c
hlor
amph
enic
ol, e
ryth
rom
ycin
, tet
racy
clin
e (o
r dox
ycyc
line
or m
inoc
yclin
e), a
nd ri
fam
pin
may
be
test
ed fo
r van
com
ycin
-res
ista
nten
tero
cocc
i (V
RE
), an
d co
nsul
tatio
n w
ith a
n in
fect
ious
dis
ease
pra
ctiti
oner
is re
com
men
ded.
(4)
For
som
e or
gani
sm/a
ntim
icro
bial
age
nt c
ombi
natio
ns,
the
abse
nce
of r
esis
tant
str
ains
pre
clud
es d
efin
ing
any
resu
lts c
ateg
orie
s ot
her
than
“sus
cept
ible
.”Fo
r st
rain
s yi
eldi
ng r
esul
ts s
ugge
stiv
e of
a “
nons
usce
ptib
le”
cate
gory
, org
anis
m id
entif
icat
ion
and
antim
icro
bial
sus
cept
ibili
ty t
est
resu
lts s
houl
d be
con
firm
ed. S
ubse
quen
tly, t
he is
olat
es s
houl
d be
sav
ed a
nd s
ubm
itted
to
a re
fere
nce
labo
rato
ry t
hat
will
con
firm
res
ults
usi
ng a
CLS
I/NC
CLS
ref
eren
ce d
ilutio
n m
etho
d.
NO
TE:
Info
rmat
ion
in b
oldf
ace
type
is c
onsi
dere
d te
ntat
ive
for o
ne y
ear.
For Use With M7-A6–MIC Testing M100-S15
117
Tabl
e 2D
Ente
roco
ccus
spp.
M7-
MIC
©Clinical and Laboratory Standards Institute. All rights reserved.
Tabl
e 2D
. (C
ontin
ued)
Test
/Rep
ort
Gro
upA
ntim
icro
bial
Age
ntM
IC (µµ
g/m
L)In
terp
retiv
e St
anda
rdC
omm
ents
SI
RPE
NIC
ILLI
NS
A AP
enic
illin
or
ampi
cilli
n≤
8≤
8- -
≥16
≥16
(5)
Am
pici
llin
is t
he c
lass
rep
rese
ntat
ive
for
ampi
cilli
n an
d am
oxic
illin
. A
mpi
cilli
nre
sults
may
be
used
to p
redi
ct s
usce
ptib
ility
to a
mox
icill
in-c
lavu
lani
c ac
id, a
mpi
cilli
n-su
lbac
tam
, pi
pera
cilli
n,
and
pipe
raci
llin-
tazo
bact
am
amon
g no
n-β-
lact
amas
e-pr
oduc
ing
ente
roco
cci.
Am
pici
llin
susc
eptib
ility
can
be
used
to
pred
ict
imip
enem
susc
eptib
ility
pro
vidi
ng th
e sp
ecie
s is
con
firm
ed to
be
E. fa
ecal
is.
(6)
Pen
icill
in s
usce
ptib
ility
may
be
used
to
pred
ict
the
susc
eptib
ility
to
ampi
cilli
n,am
oxic
illin
, am
pici
llin-
sulb
acta
m,
amox
icill
in-c
lavu
lani
c ac
id,
pipe
raci
llin,
an
dpi
pera
cilli
n-ta
zoba
ctam
for n
on-β
-lact
amas
e-pr
oduc
ing
ente
roco
cci.
(7)
Rx:
The
”su
scep
tible
” ca
tego
ry fo
r pe
nici
llin
or a
mpi
cilli
n im
plie
s th
e ne
ed fo
rhi
gh-d
ose
ther
apy
for
serio
us e
nter
ococ
cal
infe
ctio
ns.
Ent
eroc
occa
l en
doca
rditi
sre
quire
s co
mbi
ned
ther
apy
with
hig
h-do
se p
enic
illin
(or
hig
h-do
se a
mpi
cilli
n, o
rva
ncom
ycin
or t
eico
plan
in) p
lus
gent
amic
in o
r stre
ptom
ycin
for b
acte
ricid
al a
ctio
n.
(8)
Bec
ause
am
pici
llin
or p
enic
illin
res
ista
nce
amon
g en
tero
cocc
i du
e to
β-
lact
amas
e pr
oduc
tion
is n
ot re
liabl
y de
tect
ed u
sing
rout
ine
dilu
tion
met
hods
, a d
irect
,ni
troce
fin-b
ased
β-la
ctam
ase
test
is re
com
men
ded
for b
lood
and
cer
ebro
spin
al fl
uid
isol
ates
. A
posi
tive
β-la
ctam
ase
test
pre
dict
s re
sist
ance
to
peni
cilli
n, a
s w
ell
asam
ino-
, car
boxy
-, an
d ur
eido
peni
cilli
ns.
GLY
CO
PEPT
IDES
BVa
ncom
ycin
≤4
8-16
≥32
(9)
Whe
n te
stin
g va
ncom
ycin
, pl
ates
sho
uld
be h
eld
a fu
ll 24
hou
rs f
or a
ccur
ate
dete
ctio
n of
res
ista
nce.
For
isol
ates
with
van
com
ycin
MIC
s of
8-1
6 µg
/mL,
per
form
bioc
hem
ical
test
s fo
r id
entif
icat
ion
as li
sted
und
er “
Vanc
omyc
in R
esis
tanc
e” te
st a
tth
e en
d of
this
tabl
e.S
ee c
omm
ents
(2) a
nd (7
).In
v.Te
icop
lani
n ≤
816
≥32
See
com
men
ts (2
) and
(7).
LIPO
PEPT
IDES
BD
apto
myc
in≤≤
4-
-Se
e co
mm
ent (
4).
TETR
AC
YCLI
NES
See
com
men
t (3)
.C
Tetra
cycl
ine
≤4
8≥
16(1
0) O
rgan
ism
s th
at a
re s
usce
ptib
le to
tetra
cycl
ine
are
also
con
side
red
susc
eptib
leto
dox
ycyc
line
and
min
ocyc
line.
How
ever
, som
e or
gani
sms
that
are
inte
rmed
iate
or
resi
stan
t to
tetra
cycl
ine
may
be
susc
eptib
le to
dox
ycyc
line
or m
inoc
yclin
e or
bot
h.O
Dox
ycyc
line
≤4
8≥
16O
Min
ocyc
line
≤4
8≥
16M
AC
RO
LID
ESC
Ery
thro
myc
in≤
0.5
1-4
≥8
(11)
Not
rout
inel
y te
sted
and
repo
rted
on is
olat
es fr
om th
e ur
inar
y tra
ct.
118
Tabl
e 2D
Ente
roco
ccus
spp.
M7-
MIC
©Clinical and Laboratory Standards Institute. All rights reserved.
Tabl
e 2D
. (C
ontin
ued)
Test
/Rep
ort
Gro
upA
ntim
icro
bial
Age
ntM
IC (µµ
g/m
L)In
terp
retiv
e St
anda
rdC
omm
ents
SI
RFL
UO
RO
QU
INO
LON
ESU U U
Cip
roflo
xaci
nLe
voflo
xaci
nN
orflo
xaci
n
≤1
≤2
≤4
2 4 8
≥4
≥8
≥16
OG
atifl
oxac
in≤
24
≥8
(12)
Thi
s br
eakp
oint
app
lies
to is
olat
es fr
om th
e ur
inar
y tra
ct o
nly.
PHEN
ICO
LSC
Chl
oram
phen
icol
≤8
16≥
32S
ee c
omm
ent (
3).
See
com
men
t (11
).A
NSA
MYC
INS
CR
ifam
pin
≤1
2≥
4(1
3) R
x:R
ifam
pin
shou
ld n
ot b
e us
ed a
lone
for c
hem
othe
rapy
.S
ee c
omm
ent (
3).
FOSF
OM
YCIN
SU
Fosf
omyc
in≤
6412
8≥
256
(14)
For
use
with
E. f
aeca
lison
ly. T
he a
ppro
ved
met
hod
of M
IC s
usce
ptib
ility
test
ing
is a
gar
dilu
tion.
Aga
r m
edia
sho
uld
be s
uppl
emen
ted
with
25
µg/m
Lof
glu
cose
-6-p
hosp
hate
. Bro
thdi
lutio
n te
stin
g sh
ould
not
be
perfo
rmed
.N
ITR
OFU
RA
NTO
INS
UN
itrof
uran
toin
≤32
64≥
128
STR
EPTO
GR
AM
INS
BQ
uinu
pris
tin-d
alfo
pris
tin≤
12
≥4
OXA
ZOLI
DIN
ON
ESB
Line
zolid
≤2
4≥
8
January 2005 Vol. 25 No. 1
For Use With M7-A6–MIC Testing M100-S15
119©Clinical and Laboratory Standards Institute. All rights reserved.
Scre
enin
g Te
sts
for
Hig
h-Le
vel A
min
ogly
cosi
de R
esis
tanc
e an
d Va
ncom
ycin
Res
ista
nce
in E
nter
ococ
cus
spp.
Foot
note
a .E
ven
thou
gh n
ot a
s w
idel
y av
aila
ble,
dex
trose
pho
spha
te a
gar a
nd b
roth
hav
e be
en s
how
n in
lim
ited
test
ing
to p
erfo
rm c
ompa
rabl
y.
Scr
een
Test
Gen
tam
icin
HLA
RSt
rept
omyc
in H
LAR
Va
ncom
ycin
Res
ista
nce
Med
ium
BH
Iabr
oth
or a
gar
BH
Iabr
oth
or a
gar
BH
I aga
r
Ant
imic
robi
al
conc
entra
tion
500
µg/m
LB
roth
: 100
0 µg
/mL
Aga
r: 20
00 µ
g/m
L6
µg/m
L
Inoc
ulum
Gro
wth
met
hod
or d
irect
col
ony
susp
ensi
on t
oob
tain
0.5
McF
arla
nd tu
rbid
ity
Aga
r –
10 µ
Lof
a 0
.5 M
cFar
land
sus
pens
ion
spot
ted
onto
aga
r sur
face
Bro
th –
sta
ndar
d br
oth
dilu
tion
reco
mm
enda
tions
Gro
wth
met
hod
or d
irect
col
ony
susp
ensi
on to
obt
ain
0.5
McF
arla
nd tu
rbid
ity
Aga
r – 1
0 µL
of a
0.5
McF
arla
nd s
uspe
nsio
n sp
otte
don
to a
gar s
urfa
ce
Bro
th –
sta
ndar
d br
oth
dilu
tion
reco
mm
enda
tions
Gro
wth
met
hod
or d
irect
col
ony
susp
ensi
on to
obta
in 0
.5 M
cFar
land
turb
idity
1-10
µL
of a
0.5
McF
arla
nd s
uspe
nsio
n sp
otte
don
to a
gar s
urfa
ce
Incu
batio
n co
nditi
ons
35 °
C; a
mbi
ent a
ir 35
°C
; am
bien
t air
35
°C
; am
bien
t air
Incu
batio
n le
ngth
24 h
ours
24
- 48
hou
rs (i
f sus
cept
ible
at 2
4 ho
urs,
rein
cuba
te)
24 h
ours
Res
ults
Aga
r: >1
col
ony
= re
sist
ant
Bro
th: a
ny g
row
th =
resi
stan
t
Res
ista
nt –
will
not
be
syne
rgis
tic w
ith c
ell-w
all-
activ
e ag
ent (
e.g.
, am
pici
llin,
pen
icill
in,
vanc
omyc
in)
Sus
cept
ible
– w
ill b
e sy
nerg
istic
with
cel
l-wal
l-ac
tive
agen
t th
at
is
also
su
scep
tible
(e
.g.,
ampi
cilli
n, p
enic
illin
, van
com
ycin
)
Aga
r: >1
col
ony
= re
sist
ant
Bro
th: a
ny g
row
th =
resi
stan
t
Res
ista
nt –
will
not
be
syne
rgis
tic w
ith c
ell-w
all-a
ctiv
eag
ent (
e.g.
, am
pici
llin,
pen
icill
in, v
anco
myc
in)
Sus
cept
ible
– w
ill b
e sy
nerg
istic
with
cel
l-wal
l-act
ive
agen
t to
w
hich
th
e is
olat
e is
su
scep
tible
(e
.g.,
ampi
cilli
n, p
enic
illin
, van
com
ycin
)
>1 c
olon
y =
pres
umpt
ive
resi
stan
ce
Per
form
van
com
ycin
MIC
and
test
for
mot
ility
and
pigm
ent
prod
uctio
n to
di
stin
guis
h sp
ecie
s w
ithac
quire
d re
sist
ance
(Va
nAan
d Va
nB)
from
tho
sew
ith
intri
nsic
, in
term
edia
te-le
vel
resi
stan
ce
tova
ncom
ycin
(Va
nC)
such
as
E. g
allin
arum
and
E.ca
ssel
iflav
us,w
hich
ofte
n gr
ow o
n th
e va
ncom
ycin
scre
en p
late
. In
con
trast
to
othe
r en
tero
cocc
i, E.
cass
elifl
avus
,an
d E.
gal
linar
umw
ith v
anco
myc
inM
ICs
of
8-16
µg
/mL
(inte
rmed
iate
) di
ffer
from
vanc
omyc
in-r
esis
tant
en
tero
cocc
i fo
r in
fect
ion
cont
rol p
urpo
ses.
QC
Rec
omm
enda
tions
E. fa
ecal
isAT
CC
®29
212
– S
usce
ptib
le
E. fa
ecal
is A
TCC
® 5
1299
– R
esis
tant
E.
faec
alis
ATC
C®
2921
2 –
Sus
cept
ible
E.
faec
alis
ATC
C®
512
99 –
Res
ista
ntE.
faec
alis
ATC
C®
2921
2 –
Sus
cept
ible
E.
faec
alis
ATC
C®
5129
9 –
Res
ista
nt
Tabl
e 2D
Ente
roco
ccus
spp.
M7-
MIC
Tabl
e 2D
. (C
ontin
ued)
January 2005 Vol. 25 No. 1
120
Tabl
e 2E
Hae
mop
hilu
sspp
.M
7-M
IC
©Clinical and Laboratory Standards Institute. All rights reserved.
Tabl
e 2E
. M
IC In
terp
retiv
e St
anda
rds
(µµg/
mL)
for
Hae
mop
hilu
ssp
p. Min
imal
QC
Rec
omm
enda
tions
(See
Tab
le 3
Afo
r acc
epta
ble
QC
rang
es.)
Hae
mop
hilu
s in
fluen
zae
ATC
C®
4924
7H
aem
ophi
lus
influ
enza
eAT
CC
®49
766
Esch
eric
hia
coli
ATC
C®
352
18 (w
hen
test
ing
amox
icill
in-c
lavu
lani
c ac
id)
Test
/Rep
ort
Gro
upA
ntim
icro
bial
Age
ntM
IC (µµ
g/m
L)In
terp
retiv
e St
anda
rdC
omm
ents
SI
RPE
NIC
ILLI
NS
AA
mpi
cilli
n≤
12
≥4
(5)
The
resu
lts o
f am
pici
llin
susc
eptib
ility
test
s sh
ould
be
used
to p
redi
ct th
e ac
tivity
of
amox
icill
in. T
he m
ajor
ity o
f iso
late
s of
H. i
nflu
enza
eth
at a
re r
esis
tant
to a
mpi
cilli
n an
dam
oxic
illin
pro
duce
a T
EM
-type
β-la
ctam
ase.
In
mos
t ca
ses,
a d
irect
β-la
ctam
ase
test
can
prov
ide
a ra
pid
mea
ns o
f det
ectin
g am
pici
llin
and
amox
icill
in re
sist
ance
.
(6)
Rar
e β-
lact
amas
e-ne
gativ
e, a
mpi
cilli
n-re
sist
ant
(BLN
AR
) st
rain
s of
H.
influ
enza
esh
ould
be
co
nsid
ered
re
sist
ant
to
amox
icill
in-c
lavu
lani
c ac
id,
ampi
cilli
n-su
lbac
tam
,ce
facl
or,
cefa
man
dole
, ce
feta
met
, ce
foni
cid,
ce
fpro
zil,
cefu
roxi
me,
lo
raca
rbef
, an
dpi
pera
cilli
n-ta
zoba
ctam
des
pite
app
aren
t in
vitro
susc
eptib
ility
of s
ome
BLN
AR
stra
ins
toth
ese
agen
ts.
Test
ing
Con
ditio
ns
Med
ium
:B
roth
dilu
tion:
Hae
mop
hilu
sTe
st M
ediu
m
(HTM
) bro
thIn
ocul
um:
Dire
ct c
olon
y su
spen
sion
, equ
ival
ent t
o a
0.5
McF
arla
nd s
tand
ard
Incu
batio
n:35
°C
±2
degr
ees;
ambi
ent a
ir; 2
0 to
24
hour
s
Gen
eral
Com
men
ts
(1)
Onl
y re
sults
of
test
ing
with
am
pici
llin,
one
of
the
third
-gen
erat
ion
ceph
alos
porin
s, c
hlor
amph
enic
ol,
and
mer
open
em s
houl
d be
rep
orte
d ro
utin
ely
with
CS
Fis
olat
es o
f Hae
mop
hilu
s in
fluen
zae .
(2)
Am
oxic
illin
-cla
vula
nic
acid
, azi
thro
myc
in, c
larit
hrom
ycin
, cef
aclo
r, ce
fpro
zil,
lora
carb
ef, c
efdi
nir,
cefix
ime,
cef
podo
xim
e, a
nd c
efur
oxim
e ax
etil
are
oral
age
nts
that
may
be
used
as
empi
ric th
erap
y fo
r res
pira
tory
trac
t inf
ectio
ns d
ue to
Hae
mop
hilu
ssp
p. T
he re
sults
of s
usce
ptib
ility
test
s w
ith th
ese
antim
icro
bial
age
nts
are
ofte
n no
t use
ful f
or m
anag
emen
t of i
ndiv
idua
l pat
ient
s. H
owev
er, s
usce
ptib
ility
test
ing
of H
aem
ophi
lus
spp.
with
thes
e co
mpo
unds
may
be
appr
opria
te fo
rsu
rvei
llanc
e or
epi
dem
iolo
gic
stud
ies.
(3)
To m
ake
Hae
mop
hilu
sTe
st M
ediu
m: a
fres
h he
mat
in s
tock
sol
utio
n is
pre
pare
d by
dis
solv
ing
50 m
g of
hem
atin
pow
der i
n 10
0 m
Lof
0.0
1 N
(0.0
1 m
ol/L
) NaO
Hw
ith h
eat a
nd s
tirrin
g un
til th
e po
wde
r is
diss
olve
d th
orou
ghly.
Thi
rty m
illili
ters
of t
he h
emat
in s
tock
sol
utio
n is
add
ed to
1 L
of M
HB
with
5 g
of y
east
ext
ract
.A
fter a
utoc
lavi
ng a
nd c
oolin
g, c
atio
ns a
re a
dded
ase
ptic
ally,
if n
eede
d, a
s in
CA
MH
B, a
nd 3
mL
of N
AD
sto
ck s
olut
ion
(50
mg
of N
AD
dis
solv
ed in
10
mL
ofdi
still
ed w
ater
; filt
er s
teril
ized
) is
also
add
ed a
sept
ical
ly. If
sul
fona
mid
es o
r trim
etho
prim
are
to b
e te
sted
, 0.2
IU/m
Lth
ymid
ine
phos
phor
ylas
e sh
ould
als
o be
adde
d to
the
med
ium
ase
ptic
ally.
(4)
For s
ome
orga
nism
/ant
imic
robi
al a
gent
com
bina
tions
, the
abs
ence
of r
esis
tant
stra
ins
prec
lude
s de
finin
g an
y re
sults
cat
egor
ies
othe
r tha
n “s
usce
ptib
le.”
For
stra
ins
yiel
ding
res
ults
sug
gest
ive
of a
“no
nsus
cept
ible
” ca
tego
ry,
orga
nism
iden
tific
atio
n an
d an
timic
robi
al s
usce
ptib
ility
tes
t re
sults
sho
uld
be c
onfir
med
.S
ubse
quen
tly, t
he is
olat
es s
houl
d be
sav
ed a
nd s
ubm
itted
to a
refe
renc
e la
bora
tory
that
will
con
firm
resu
lts u
sing
a C
LSI/N
CC
LS re
fere
nce
dilu
tion
met
hod.
NO
TE:
Info
rmat
ion
in b
oldf
ace
type
is c
onsi
dere
d te
ntat
ive
for o
ne y
ear.
For Use With M7-A6–MIC Testing M100-S15
121
Tabl
e 2E
Hae
mop
hilu
sspp
.M
7-M
IC
©Clinical and Laboratory Standards Institute. All rights reserved.
Tabl
e 2E
. (C
ontin
ued)
Test
/Rep
ort
Gro
upA
ntim
icro
bial
Age
ntM
IC (µµ
g/m
L)In
terp
retiv
e St
anda
rdC
omm
ents
SI
Rββ -
LAC
TAM
/ββ-L
AC
TAM
ASE
INH
IBIT
OR
CO
MB
INAT
ION
SS
ee c
omm
ent (
6).
BA
mpi
cilli
n-su
lbac
tam
≤2/
1-
≥4/
2C
Am
oxic
illin
-cla
vula
nic
acid
≤4/
2 -
≥8/
4O
Pip
erac
illin
-tazo
bact
am≤
1/4
- ≥
2/4
CEP
HEM
S (P
AR
ENTE
RA
L) (
Incl
udin
g ce
phal
ospo
rins
I, II,
III,
and
IV. P
leas
e re
fer
to G
loss
ary
I.)
See
com
men
t (6)
.
B B B B
Cef
otax
ime
or
cefta
zidi
me
orce
ftizo
xim
e or
ce
ftria
xone
≤2
≤2
≤2
≤2
- - - -
- - - -
See
com
men
t (4)
.
BC
efur
oxim
e so
dium
(par
ente
ral)
≤4
8≥
16C
Cef
onic
id≤
48
≥16
OC
efam
ando
le≤
48
≥16
OC
efep
ime
≤2
--
See
com
men
t (4)
.C
EPH
EMS
(OR
AL)
C C C
Cef
aclo
r or
cefp
rozi
l or
lora
carb
ef
≤8
≤8
≤8
16 16 16
≥32
≥32
≥32
C C C
Cef
dini
r or
cefix
ime
orce
fpod
oxim
e
≤1
≤1
≤2
- - -
- - -
See
com
men
t (4)
.
CC
efur
oxim
e ax
etil
(ora
l)≤
48
≥16
OC
eftib
uten
≤2
--
See
com
men
t (4)
.In
v.C
efet
amet
≤4
8≥
16C
AR
BA
PEN
EMS
BM
erop
enem
≤0.
5-
-S
ee c
omm
ent (
4).
C CE
rtape
nem
or
imip
enem
≤0.
5≤
4- -
- -S
ee c
omm
ent (
4).
MO
NO
BA
CTA
MS
CA
ztre
onam
≤2
--
See
com
men
t (4)
.M
AC
RO
LID
ESC C
Azi
thro
myc
in o
rcl
arith
rom
ycin
≤4
≤8
- 16-
≥32
See
com
men
t (4)
.
KET
OLI
DES
CTe
lithr
omyc
in≤≤
48
≥16
TETR
AC
YCLI
NES
CTe
tracy
clin
e≤
24
≥8
(7)
Org
anis
ms
that
are
sus
cept
ible
to te
tracy
clin
e ar
e al
so c
onsi
dere
dsu
scep
tible
to d
oxyc
yclin
e an
d m
inoc
yclin
e.
January 2005 Vol. 25 No. 1
122
Tabl
e 2E
Hae
mop
hilu
sspp
.M
7-M
IC
Tabl
e 2E
. (C
ontin
ued)
Test
/Rep
ort
Gro
upA
ntim
icro
bial
Age
ntM
IC (µµ
g/m
L)In
terp
retiv
e St
anda
rdC
omm
ents
SI
RFL
UO
RO
QU
INO
LON
ESC
C C C C C C
Cip
roflo
xaci
n or
gatif
loxa
cin
orle
voflo
xaci
n or
lom
eflo
xaci
n or
mox
iflox
acin
or
oflo
xaci
n or
spar
floxa
cin
≤1
≤1
≤2
≤2
≤1
≤2
≤0.
25
- - - - - - -
- - - - - - -
See
com
men
t (4)
CG
emifl
oxac
in≤
0.12
--
OG
repa
floxa
cin
≤0.
5-
-O
Trov
aflo
xaci
n≤
1-
-In
v.Fl
erox
acin
≤2
--
FOLA
TE P
ATH
WAY
INH
IBIT
OR
SA
Trim
etho
prim
-sul
fam
etho
xazo
le≤
0.5/
9.5
1/19
-2/3
8≥
4/76
PHEN
ICO
LSB
Chl
oram
phen
icol
≤2
4≥
8A
NSA
MYC
INS
CR
ifam
pin
≤1
2≥
4
©Clinical and Laboratory Standards Institute. All rights reserved.
For Use With M7-A6–MIC Testing M100-S15
123©Clinical and Laboratory Standards Institute. All rights reserved.
This page is intentionally left blank.
January 2005 Vol. 25 No. 1
124
Tabl
e 2F
Nei
sser
ia g
onor
rhoe
aeM
7-M
IC
©Clinical and Laboratory Standards Institute. All rights reserved.
Tabl
e 2F
. M
IC In
terp
retiv
e St
anda
rds
(µµg/
mL)
for
Nei
sser
ia g
onor
rhoe
ae
Min
imal
QC
Rec
omm
enda
tions
(See
Tab
le 3
Afo
r ac
cept
able
QC
rang
es.)
Nei
sser
ia g
onor
rhoe
aeAT
CC
®49
226
Test
ing
Con
ditio
ns
Med
ium
:A
gar d
ilutio
n: G
C a
gar b
ase
and
1% d
efin
ed g
row
th s
uppl
emen
t. Th
e us
e of
a cy
stei
ne-fr
ee
supp
lem
ent
is
requ
ired
for
agar
di
lutio
n te
sts
with
carb
apen
ems
and
clav
ulan
ate.
C
yste
ine-
cont
aini
ng
defin
ed
grow
thsu
pple
men
ts d
o no
tsig
nific
antly
alte
r dilu
tion
test
resu
lts w
ith o
ther
dru
gs.
Inoc
ulum
:D
irect
col
ony
susp
ensi
on, e
quiv
alen
t to
a 0.
5 M
cFar
land
sta
ndar
dIn
cuba
tion:
35 °
C ±
2 de
gree
s; 5
% C
O2;
20
to 2
4 ho
urs
Gen
eral
Com
men
ts
(1)
The
reco
mm
ende
d m
ediu
m fo
r te
stin
g N
. gon
orrh
oeae
cons
ists
of G
C a
gar
to w
hich
a 1
% d
efin
ed g
row
th s
uppl
emen
t (1.
1 g
L-cy
stei
ne, 0
.03
g gu
anin
eH
CL,
3 m
g th
iam
ine
HC
L, 1
3 m
g PA
BA
, 0.0
1 g
B12
, 0.1
g c
ocar
boxy
lase
, 0.2
5 g
NA
D, 1
g a
deni
ne, 1
0 g
L-gl
utam
ine,
100
g g
luco
se, 0
.02
g fe
rric
nitr
ate
[in 1
LH
2O])
is a
dded
afte
r aut
ocla
ving
.
(2)
For s
ome
orga
nism
/ant
imic
robi
al a
gent
com
bina
tions
, the
abs
ence
of r
esis
tant
stra
ins
prec
lude
s de
finin
g an
y re
sults
cat
egor
ies
othe
r tha
n “s
usce
ptib
le.”
For
stra
ins
yiel
ding
resu
lts s
ugge
stiv
e of
a “n
onsu
scep
tible
” cat
egor
y, o
rgan
ism
iden
tific
atio
n an
d an
timic
robi
al s
usce
ptib
ility
test
resu
lts s
houl
d be
con
firm
ed. S
ubse
quen
tly, t
heis
olat
es s
houl
d be
sav
ed a
nd s
ubm
itted
to a
refe
renc
e la
bora
tory
that
will
con
firm
resu
lts u
sing
a C
LSI/N
CC
LS re
fere
nce
dilu
tion
met
hod.
NO
TE:
Info
rmat
ion
in b
oldf
ace
type
is c
onsi
dere
d te
ntat
ive
for o
ne y
ear.
For Use With M7-A6–MIC Testing M100-S15
125
Tabl
e 2F
Nei
sser
ia g
onor
rhoe
aeM
7-M
IC
©Clinical and Laboratory Standards Institute. All rights reserved.
Tabl
e 2F
. (C
ontin
ued)
Test
/Rep
ort
Gro
upA
ntim
icro
bial
Age
ntM
IC (µµ
g/m
L)In
terp
retiv
e St
anda
rdC
omm
ents
SI
RPE
NIC
ILLI
NS
CP
enic
illin
≤0.
060.
12-1
≥2
(3)
Apo
sitiv
e β-
lact
amas
e te
st p
redi
cts
resi
stan
ce to
pen
icill
in, a
mpi
cilli
n, a
ndam
oxic
illin
.
(4)
Aβ-
lact
amas
e te
st w
ill d
etec
t on
e fo
rm o
f pe
nici
llin
resi
stan
ce i
n N
.go
norrh
oeae
and
also
may
be
used
to
prov
ide
epid
emio
logi
c in
form
atio
n.St
rain
s w
ith c
hrom
osom
ally
med
iate
d re
sist
ance
can
be
dete
cted
onl
y by
the
disk
diff
usio
n m
etho
d or
the
agar
dilu
tion
MIC
met
hod.
CEP
HEM
S (P
AR
ENTE
RA
L) (
Incl
udin
g ce
phal
ospo
rins
I, II,
III,
and
IV. P
leas
e re
fer
to G
loss
ary
I.)C C C
Cef
otax
ime
orce
ftizo
xim
e or
ceftr
iaxo
ne
≤0.
5≤
0.5
≤0.
25
– – –
– – –
See
com
men
t (2)
.
C C C C
Cef
met
azol
e C
efot
etan
C
efox
itin
Cef
urox
ime
sodi
um (p
aren
tera
l)
≤2
≤2
≤2
≤1
4 4 4 2
≥8
≥8
≥8
≥4
OC
efep
ime
≤0.
5–
–S
ee c
omm
ent (
2).
OC
efta
zidi
me
≤0.
5–
–S
ee c
omm
ent (
2).
CEP
HEM
S (O
RA
L)C C
Cef
ixim
e or
ce
fpod
oxim
e≤
0.25
≤0.
5– –
– –S
ee c
omm
ent (
2).
Inv.
Cef
etam
et≤
0.5
––
See
com
men
t (2)
.TE
TRA
CYC
LIN
ESC
Tetra
cycl
ine
≤0.
250.
5-1
≥2
(5)
Org
anis
ms
that
are
sus
cept
ible
to
tetra
cycl
ine
are
also
con
side
red
susc
eptib
le to
dox
ycyc
line
and
min
ocyc
line.
FLU
OR
OQ
UIN
OLO
NES
C C C
Cip
roflo
xaci
n or
gatif
loxa
cin
orof
loxa
cin
≤0.
06≤
0.12
5≤
0.25
0.12
-0.5
0.25
0.5-
1
≥1
≥0.
5≥
2O
Eno
xaci
n≤
0.5
1≥
2O
Gre
paflo
xaci
n≤
0.06
0.
12-0
.5≥
1O
Lom
eflo
xaci
n≤
0.12
0.25
-1≥
2O
Trov
aflo
xaci
n≤
0.25
–
–S
ee c
omm
ent (
2).
Inv.
Fler
oxac
in≤
0.25
0.5
≥1
AM
INO
CYC
LITO
LS
C
Spec
tinom
ycin
≤32
64≥
128
January 2005 Vol. 25 No. 1
126
Tabl
e 2G
Stre
ptoc
occu
s pne
umon
iae
M7-
MIC
©Clinical and Laboratory Standards Institute. All rights reserved.
Tabl
e 2G
. M
IC In
terp
retiv
e St
anda
rds
(µµg/
mL)
for
Stre
ptoc
occu
s pn
eum
onia
e
Test
ing
Con
ditio
ns
Med
ium
:B
roth
dilu
tion:
Cat
ion-
adju
sted
Mue
ller-
Hin
ton
brot
h w
ith l
ysed
hor
se b
lood
(LH
B) (
2 to
5%
v/v
)In
ocul
um:
Dire
ct c
olon
y su
spen
sion
, equ
ival
ent t
o a
0.5
McF
arla
nd s
tand
ard
Incu
batio
n:35
°C
±2
degr
ees;
am
bien
t air;
20
to 2
4 ho
urs
Min
imal
Q
C
Rec
omm
enda
tions
(See
Ta
ble
3Afo
rac
cept
able
QC
rang
es).
Stre
ptoc
occu
s pn
eum
onia
eAT
CC
®49
619
Test
/Rep
ort
Gro
upA
ntim
icro
bial
Age
ntM
IC (µµ
g/m
L)In
terp
retiv
e St
anda
rdC
omm
ents
SI
RPE
NIC
ILLI
NS
(4)
Apn
eum
ococ
cal
isol
ate
that
is
susc
eptib
le t
o pe
nici
llin
can
beco
nsid
ered
sus
cept
ible
to
ampi
cilli
n, a
mox
icill
in,
amox
icill
in-c
lavu
lani
cac
id,
ampi
cilli
n-su
lbac
tam
, ce
facl
or,
cefd
inir,
ce
fepi
me,
ce
feta
met
,ce
fixim
e,
cefo
taxi
me,
ce
fpro
zil,
cefti
bute
n,
ceftr
iaxo
ne,
cefu
roxi
me,
cefp
odox
ime,
ce
ftizo
xim
e,
erta
pene
m,
imip
enem
, lo
raca
rbef
, an
dm
erop
enem
for
app
rove
d in
dica
tions
. Te
stin
g of
am
pici
llin,
am
pici
llin-
sulb
acta
m,
cefti
bute
n,
cefe
tam
et,
cefti
zoxi
me,
an
d ce
fixim
e ag
ains
tpe
nici
llin-
inte
rmed
iate
or p
enic
illin
-res
ista
nt is
olat
es is
not
reco
mm
ende
d,be
caus
e re
liabl
e in
terp
retiv
e cr
iteria
for t
hose
age
nts
with
S. p
neum
onia
ear
e no
t av
aila
ble.
Phy
sici
ans
shou
ld b
e in
form
ed t
hat
clin
ical
res
pons
era
tes
with
thes
e ag
ents
may
be
low
er in
stra
ins
that
are
not
sus
cept
ible
tope
nici
llin.
See
com
men
t (1
).A
Pen
icill
in≤
0.06
0.12
-1≥
2(5
) R
x:H
igh
dose
s of
intra
veno
us p
enic
illin
s (e
.g.,
at le
ast 2
mill
ion
units
ever
y fo
ur h
ours
in a
dults
with
nor
mal
rena
l fun
ctio
n) o
r sim
ilarly
am
pici
llin
are
effe
ctiv
e in
tre
atin
g pn
eum
ococ
cal p
neum
onia
due
to
stra
ins
in t
hein
term
edia
te c
ateg
ory.
C CA
mox
icill
in (n
onm
enin
gitis
) or
amox
icill
in-c
lavu
lani
c ac
id
(non
men
ingi
tis)
≤2
≤2/
14 4/
2≥
8≥
8/4
Gen
eral
Com
men
ts
(1)
Onl
y re
sults
of t
estin
g w
ith p
enic
illin
, cef
otax
ime,
cef
triax
one,
mer
open
em, a
nd v
anco
myc
in s
houl
d be
repo
rted
rout
inel
y fo
r CS
F is
olat
es o
f S. p
neum
onia
e.
(2)
Inst
ruct
ions
for
pre
para
tion
of ly
sed
hors
e bl
ood
are
prov
ided
in C
LSI/N
CC
LS d
ocum
ent
M7—
Met
hods
for
Dilu
tion
Antim
icro
bial
Sus
cept
ibilit
y Te
sts
for
Bact
eria
That
Gro
w A
erob
ical
ly.
(3)
For s
ome
orga
nism
/ant
imic
robi
al a
gent
com
bina
tions
, the
abs
ence
of r
esis
tant
stra
ins
prec
lude
s de
finin
g an
y re
sults
cat
egor
ies
othe
r tha
n “s
usce
ptib
le.”
For
stra
ins
yiel
ding
res
ults
sug
gest
ive
of a
“no
nsus
cept
ible
” ca
tego
ry, o
rgan
ism
iden
tific
atio
n an
d an
timic
robi
al s
usce
ptib
ility
test
res
ults
sho
uld
be c
onfir
med
.S
ubse
quen
tly, t
he is
olat
es s
houl
d be
sav
ed a
nd s
ubm
itted
to a
refe
renc
e la
bora
tory
that
will
con
firm
resu
lts u
sing
a C
LSI/N
CC
LS re
fere
nce
dilu
tion
met
hod .
NO
TE:
Info
rmat
ion
in b
oldf
ace
type
is c
onsi
dere
d te
ntat
ive
for o
ne y
ear.
For Use With M7-A6–MIC Testing M100-S15
127
Tabl
e 2G
Stre
ptoc
occu
s pne
umon
iae
M7-
MIC
©Clinical and Laboratory Standards Institute. All rights reserved.
Tabl
e 2G
. (C
ontin
ued)
Test
/Rep
ort
Gro
upA
ntim
icro
bial
Age
ntM
IC (µµ
g/m
L)In
terp
retiv
e St
anda
rd
Com
men
ts
SI
RC
EPH
EMS
(PA
REN
TER
AL)
(In
clud
ing
ceph
alos
porin
s I,
II, II
I, an
d IV
. Ple
ase
refe
r to
Glo
ssar
y I.)
See
com
men
t (1)
.B
Cef
epim
e (n
onm
enin
gitis
)≤
12
≥4
(6)
Onl
y re
port
inte
rpre
tatio
ns fo
r non
men
ingi
tis a
nd in
clud
e th
e no
nmen
ingi
tis n
otat
ion
on th
e re
port.
The
re is
not
a U
.S. F
DA
-app
rove
d in
dica
tion
for
the
use
of c
efep
ime
for
men
ingi
tis.
B
Cef
epim
e (m
enin
gitis
)≤
0.5
1 ≥
2B B
Cef
otax
ime
(men
ingi
tis) o
rce
ftria
xone
(men
ingi
tis)
≤0.
5≤
0.5
1 1≥
2≥
2(7
) Fo
r CS
F is
olat
es, r
epor
t onl
y m
enin
gitis
inte
rpre
tatio
ns.
(8)
Rx:
Use
of c
efot
axim
e or
cef
triax
one
in m
enin
gitis
req
uire
s th
erap
y w
ith m
axim
umdo
ses.
B BC
efot
axim
e (n
onm
enin
gitis
) or
ceftr
iaxo
ne (n
onm
enin
gitis
)≤
1≤
12 2
≥4
≥4
(9)
For a
ll is
olat
es o
ther
than
thos
e fro
m C
SF,
repo
rt in
terp
reta
tions
for b
oth
men
ingi
tisan
d no
nmen
ingi
tis.
(10)
Rx:
For
cefo
taxi
me,
use
of
inte
rpre
tive
crite
ria f
or n
onm
enin
gitis
req
uire
s do
ses
appr
opria
te fo
r se
rious
pne
umoc
occa
l inf
ectio
ns (
e.g.
, at l
east
1 g
[adu
lts] o
r 50
mg/
kg[c
hild
ren]
eve
ry e
ight
hou
rs o
r mor
e fre
quen
tly).
C
Cef
urox
ime
sodi
um (p
aren
tera
l)≤
0.5
1 ≥
2C
EPH
EMS
(OR
AL)
OC
efac
lor
≤1
2 ≥
4O
Cef
dini
r≤
0.5
1 ≥
2O
Cef
podo
xim
e≤
0.5
1 ≥
2O
C
efpr
ozil
≤2
4 ≥
8O
C
efur
oxim
e ax
etil
(ora
l)≤
12
≥4
OLo
raca
rbef
≤
24
≥8
CA
RB
APE
NEM
SS
ee c
omm
ent (
1).
BM
erop
enem
≤0.
250.
5≥
1C
Erta
pene
m≤
12
≥4
CIm
ipen
em≤
0.12
0.25
-0.5
≥1
GLY
CO
PEPT
IDES
See
com
men
t (1)
.B
Vanc
omyc
in≤
1-
- S
ee c
omm
ent (
3).
MA
CR
OLI
DES
(11)
Sus
cept
ibili
ty a
nd re
sist
ance
to a
zith
rom
ycin
, cla
rithr
omyc
in, a
nd d
irith
rom
ycin
can
be p
redi
cted
by
usin
g er
ythr
omyc
in.
(12)
Not
rout
inel
y re
porte
d on
isol
ates
from
the
urin
ary
tract
.A
Ery
thro
myc
in
≤0.
250.
5≥
1O
A
zith
rom
ycin
≤0.
51
≥2
O
Cla
rithr
omyc
in≤
0.25
0.5
≥1
OD
irith
rom
ycin
≤0.
51
≥2
KET
OLI
DES
BTe
lithr
omyc
in≤
12
≥4
TETR
AC
YCLI
NES
BTe
tracy
clin
e ≤
24
≥8
(13)
O
rgan
ism
s th
at a
re s
usce
ptib
le to
tetra
cycl
ine
are
also
con
side
red
susc
eptib
le to
doxy
cycl
ine
and
min
ocyc
line.
January 2005 Vol. 25 No. 1
128
Tabl
e 2G
Stre
ptoc
occu
s pne
umon
iae
M7-
MIC
©Clinical and Laboratory Standards Institute. All rights reserved.
Tabl
e 2G
. (C
ontin
ued)
Test
/Rep
ort
Gro
upA
ntim
icro
bial
Age
ntM
IC (µµ
g/m
L)In
terp
retiv
e St
anda
rd
Com
men
ts
SI
RFL
UO
RO
QU
INO
LON
ESB B B B B
B
Gat
iflox
acin
G
emifl
oxac
in
Levo
floxa
cin
Mox
iflox
acin
Spar
floxa
cin
Oflo
xaci
n
≤1
≤0.
12≤
2≤
1≤
0.5
≤2
20.
25
4 2 1 4
≥4
≥0.
5≥
8≥
4≥
2≥
8O
Gre
paflo
xaci
n≤
0.5
1≥
2O
Trov
aflo
xaci
n≤
12
≥4
FOLA
TE P
ATH
WAY
INH
IBIT
OR
SA
Trim
etho
prim
-sul
fam
etho
xazo
le≤
0.5/
9.5
1/19
-2/3
8≥
4/76
PHEN
ICO
LSC
Chl
oram
phen
icol
≤4
-≥
8S
ee c
omm
ent (
12).
AN
SAM
YCIN
SC
Rifa
mpi
n≤
12
≥4
(14)
Rx:
Rifa
mpi
n sh
ould
not
be
used
alo
ne fo
r che
mot
hera
py.
LIN
CO
SAM
IDES
BC
linda
myc
in≤
0.25
0.5
≥1
See
com
men
t (12
).ST
REP
TOG
RA
MIN
SO
Qui
nupr
istin
-dal
fopr
istin
≤1
2≥
4O
XAZO
LID
INO
NES
CLi
nezo
lid≤
2-
-S
ee c
omm
ent (
3).
For Use With M7-A6–MIC Testing M100-S15
129©Clinical and Laboratory Standards Institute. All rights reserved.
This page is intentionally left blank.
January 2005 Vol. 25 No. 1
130
Tabl
e 2H
Stre
ptoc
occu
sspp
. O
ther
Tha
n S.
pne
umon
iae
M7-
MIC
©Clinical and Laboratory Standards Institute. All rights reserved.
Tabl
e 2H
. M
IC In
terp
retiv
e St
anda
rds
(µµg/
mL)
for
Stre
ptoc
occu
ssp
p. O
ther
Tha
n St
rept
ococ
cus
pneu
mon
iae
Min
imal
QC
Rec
omm
enda
tions
(See
Tab
le 3
Afo
rac
cept
able
QC
rang
es.)
Stre
ptoc
occu
s pn
eum
onia
eAT
CC
®49
619
Test
ing
Con
ditio
ns
Med
ium
:B
roth
dilu
tion:
Cat
ion-
adju
sted
Mue
ller-
Hin
ton
brot
h w
ith ly
sed
hors
e bl
ood
(2 to
5%
v/v
); C
AM
HB
sup
plem
ente
d to
50
µµ g/m
Lca
lciu
m fo
r da
ptom
ycin
Aga
r dilu
tion:
Mue
ller-
Hin
ton
with
she
ep b
lood
(5%
v/v
) (w
hen
test
ing
asu
lfona
mid
e, ly
sed
hors
e bl
ood
shou
ld b
e us
ed);
agar
dilu
tion
is
curr
ently
not
rec
omm
ende
d fo
r da
ptom
ycin
. In
ocul
um:
Dire
ct c
olon
y su
spen
sion
, equ
ival
ent t
o a
0.5
McF
arla
nd s
tand
ard
Incu
batio
n:35
°C
±2
degr
ees;
am
bien
t air;
20
to 2
4 ho
urs
(CO
2if
nece
ssar
y fo
rgr
owth
with
aga
r dilu
tion)
Gen
eral
Com
men
ts
(1)
For
this
tabl
e, th
e be
ta-h
emol
ytic
gro
up in
clud
es th
e la
rge-
colo
ny-fo
rmin
g py
ogen
ic s
train
s of
stre
ptoc
occi
with
Gro
up A
(S. p
yoge
nes)
, C, o
r G a
ntig
ens
and
stra
ins
with
Gro
up B
(S. a
gala
ctia
e)an
tigen
. Sm
all-c
olon
y-fo
rmin
g be
ta-h
emol
ytic
stra
ins
with
Gro
up A
, C, F
, or G
ant
igen
s (S
. ang
inos
us, p
revi
ousl
y te
rmed
“S. m
illeri”
) are
con
side
red
part
of th
e vi
ridan
s gr
oup,
and
inte
rpre
tive
crite
ria fo
r the
viri
dans
gro
up s
houl
d be
use
d. T
he v
irida
ns g
roup
als
o in
clud
es S
. miti
s, S
. ora
lis, S
. san
guis
, S. s
aliv
ariu
s, S
. int
erm
ediu
s, S
. con
stel
latu
s, S
. mut
ans,
and
S. b
ovis
.
(2)
Sus
cept
ibili
ty te
stin
g of
pen
icill
ins
and
othe
r β-la
ctam
s ap
prov
ed b
y th
e FD
Afo
r tre
atm
ent o
f Gro
up A
and
Gro
up B
stre
ptoc
occi
is n
ot n
eces
sary
for c
linic
al p
urpo
ses
and
need
not
be
done
rout
inel
y, s
ince
as
with
van
com
ycin
, res
ista
nt s
train
s ha
ve n
ot b
een
reco
gniz
ed. B
reak
poin
ts a
nd in
terp
retiv
e cr
iteria
are
pro
vide
d fo
r pha
rmac
eutic
al d
evel
opm
ent,
epid
emio
logy
, or m
onito
ring
for e
mer
ging
resi
stan
ce. A
ny s
train
s fo
und
to b
e no
nsus
cept
ible
sho
uld
be re
ferr
ed to
a re
fere
nce
labo
rato
ry fo
r con
firm
atio
n.
(3)
Inte
rpre
tive
crite
ria fo
r st
rept
ococ
ci o
ther
than
S. p
neum
onia
ear
e pr
opos
ed b
ased
on
popu
latio
n di
strib
utio
ns o
f var
ious
spe
cies
, pha
rmac
okin
etic
s of
the
antim
icro
bial
age
nts,
pre
viou
sly
publ
ishe
d lit
erat
ure,
and
the
clin
ical
exp
erie
nce
of c
erta
in m
embe
rs o
f the
sub
com
mitt
ee. S
yste
mat
ical
ly c
olle
cted
clin
ical
dat
a w
ere
not a
vaila
ble
for r
evie
w w
ith m
any
of th
e co
mpo
unds
inth
e gr
oup.
(4)
Inst
ruct
ions
for p
repa
ratio
n of
lyse
d ho
rse
bloo
d ar
e pr
ovid
ed in
CLS
I/NC
CLS
doc
umen
t M7—
Met
hods
for D
ilutio
n An
timic
robi
al S
usce
ptib
ility
Test
s fo
r Bac
teria
Tha
t Gro
w A
erob
ical
ly.
(5)
For s
ome
orga
nism
/ant
imic
robi
al a
gent
com
bina
tions
, the
abs
ence
of r
esis
tant
stra
ins
prec
lude
s de
finin
g an
y re
sults
cat
egor
ies
othe
r tha
n “s
usce
ptib
le.”
For
stra
ins
yiel
ding
resu
lts s
ugge
stiv
eof
a “
nons
usce
ptib
le”
cate
gory
, or
gani
sm id
entif
icat
ion
and
antim
icro
bial
sus
cept
ibili
ty t
est
resu
lts s
houl
d be
con
firm
ed.
Sub
sequ
ently
, th
e is
olat
es s
houl
d be
sav
ed a
nd s
ubm
itted
to
are
fere
nce
labo
rato
ry th
at w
ill c
onfir
m re
sults
usi
ng a
CLS
I/NC
CLS
refe
renc
e di
lutio
n m
etho
d.
NO
TE:
Info
rmat
ion
in b
oldf
ace
type
is c
onsi
dere
d te
ntat
ive
for o
ne y
ear.
Test
/Rep
ort
Gro
upA
ntim
icro
bial
Age
ntM
IC (µµ
g/m
L)In
terp
retiv
e St
anda
rdC
omm
ents
SI
RPE
NIC
ILLI
NS
(6)
Ast
rept
ococ
cal i
sola
te th
at is
sus
cept
ible
to p
enic
illin
can
be
cons
ider
edsu
scep
tible
to
ampi
cilli
n, a
mox
icill
in,
amox
icill
in-c
lavu
lani
c ac
id,
ampi
cilli
n-su
lbac
tam
, ce
facl
or,
cefa
zolin
, ce
fdin
ir,
cefe
pim
e,
cefp
rozi
l, ce
fota
xim
e,ce
ftibu
ten
(Gro
up A
stre
ptoc
occi
onl
y), c
eftri
axon
e, c
efur
oxim
e, c
efpo
doxi
me,
cefti
zoxi
me,
ce
phra
dine
, ce
phal
othi
n,
ceph
apiri
n,
erta
pene
m,
imip
enem
,lo
raca
rbef
, and
mer
open
em fo
r ap
prov
ed in
dica
tions
, and
nee
d no
t be
test
edag
ains
t tho
se a
gent
s.A A
Pen
icill
in (b
eta-
hem
olyt
ic g
roup
) or
ampi
cilli
n (b
eta-
hem
olyt
ic g
roup
)≤
0.12
≤0.
25- -
- -S
ee c
omm
ent (
5).
(7)
Stra
ins
of b
eta-
hem
olyt
ic s
trept
ococ
ci w
ith p
enic
illin
MIC
s of
gre
ater
than
0.12
µg/
mL
or a
mpi
cilli
n M
ICs
of g
reat
er t
han
0.25
µg/
mL
have
not
bee
nob
serv
ed; s
ubm
it su
ch s
train
s to
a re
fere
nce
labo
rato
ry.
For Use With M7-A6–MIC Testing M100-S15
131©Clinical and Laboratory Standards Institute. All rights reserved.
Tabl
e 2H
Stre
ptoc
occu
sspp
. O
ther
Tha
nS.
pne
umon
iae
M7-
MIC
Tabl
e 2H
. (C
ontin
ued)
Test
/Rep
ort
Gro
upA
ntim
icro
bial
Age
ntM
IC (µµ
g/m
L)In
terp
retiv
e St
anda
rdC
omm
ents
SI
RPE
NIC
ILLI
NS
(Con
tinue
d)A A
Pen
icill
in (v
irida
ns g
roup
) or
ampi
cilli
n (v
irida
ns g
roup
) ≤
0.12
≤0.
250.
25-2
0.5-
4 ≥
4≥
8(8
) R
x:P
enic
illin
- or
am
pici
llin-
inte
rmed
iate
iso
late
s m
ay r
equi
re c
ombi
ned
ther
apy
with
an
amin
ogly
cosi
de fo
r bac
teric
idal
act
ion.
CEP
HEM
S (P
AR
ENTE
RA
L) (I
nclu
ding
cep
halo
spor
ins
I, II,
III,
and
IV. P
leas
e re
fer
to G
loss
ary
I.)S
ee c
omm
ent (
6).
C C C C C
C
Cef
epim
e (b
eta-
hem
olyt
ic g
roup
) or
cefo
taxi
me
(bet
a-he
mol
ytic
gro
up) o
rce
ftria
xone
(bet
a-he
mol
ytic
gro
up)
Cef
epim
e (v
irida
ns g
roup
) or
cefo
taxi
me
(viri
dans
gro
up) o
rce
ftria
xone
(viri
dans
gro
up)
≤0.
5≤
0.5
≤0.
5
≤1
≤1
≤1
- - - 2 2 2
- - - ≥4
≥4
≥4
See
com
men
t (5)
.
CA
RB
APE
NEM
SO
Erta
pene
m≤
1
--
(9) B
reak
poin
ts a
re fo
r rep
ortin
g ag
ains
t bet
a-he
mol
ytic
stre
ptoc
occi
onl
y.
See
com
men
t (5)
.O
Mer
open
em≤
0.5
--
See
com
men
t (5)
.G
LYC
OPE
PTID
ESB
Vanc
omyc
in≤
1-
- S
ee c
omm
ent (
5).
LIPO
PEPT
IDES
CD
apto
myc
in≤≤
1
--
See
com
men
t (5)
.M
AC
RO
LID
ES(1
0)
S
usce
ptib
ility
an
d re
sist
ance
to
az
ithro
myc
in,
clar
ithro
myc
in,
and
dirit
hrom
ycin
can
be
pred
icte
d by
test
ing
eryt
hrom
ycin
.
(11)
Not
rout
inel
y re
porte
d on
isol
ates
from
the
urin
ary
tract
.A
Ery
thro
myc
in≤
0.25
0.5
≥1
(12)
Rx:
Rec
omm
enda
tions
for
int
rapa
rtum
pro
phyl
axis
for
Gro
up B
stre
ptoc
occi
are
pen
icill
in o
r am
pici
llin.
Whi
le c
efaz
olin
is r
ecom
men
ded
for p
enic
illin
-alle
rgic
wom
en a
t low
risk
for a
naph
ylax
is, t
hose
at h
igh
risk
for
anap
hyla
xis
may
re
ceiv
e cl
inda
myc
in
or
erth
rom
ycin
. G
roup
B
stre
ptoc
occi
are
sus
cept
ible
to
ampi
cilli
n, p
enic
illin
, an
d ce
fazo
lin,
but
may
be
resi
stan
t to
clin
dam
ycin
and
/or
eryt
hrom
ycin
. W
hen
a gr
oup
Bst
rept
ococ
cus
is i
sola
ted
from
a p
regn
ant
wom
an w
ith s
ever
e pe
nici
llin
alle
rgy
(hig
h ris
k fo
r an
aphy
laxi
s), c
linda
myc
in a
nd e
ryth
rom
ycin
sho
uld
be te
sted
and
rep
orte
d.O
Azi
thro
myc
in≤
0.5
1 ≥
2O
Cla
rithr
omyc
in≤
0.25
0.5
≥1
OD
irith
rom
ycin
≤0.
51
≥2
TETR
AC
YCLI
NES
OTe
tracy
clin
e ≤
24
≥8
(13)
Org
anis
ms
that
ar
e su
scep
tible
to
te
tracy
clin
e ar
e al
so
cons
ider
edsu
scep
tible
to d
oxyc
yclin
e an
d m
inoc
yclin
e.
January 2005 Vol. 25 No. 1
©Clinical and Laboratory Standards Institute. All rights reserved.132
Test
/Rep
ort
Gro
upA
ntim
icro
bial
Age
ntM
IC (µµ
g/m
L)In
terp
retiv
e St
anda
rdC
omm
ents
SI
RFL
UO
RO
QU
INO
LON
ESC
Levo
floxa
cin
≤2
4≥
8C
Oflo
xaci
n≤
2 4
≥8
See
com
men
t (9)
.O
Gat
iflox
acin
≤1
2≥
4 S
ee c
omm
ent (
9).
OG
repa
floxa
cin
≤0.
51
≥2
OTr
ovaf
loxa
cin
≤1
2≥
4PH
ENIC
OLS
BC
hlor
amph
enic
ol≤
48
≥16
See
com
men
t (11
).LI
NC
OSA
MID
ESB
Clin
dam
ycin
≤0.
250.
5≥
1S
ee c
omm
ents
(11)
and
(12)
.(1
4) M
acro
lide-
resi
stan
t is
olat
es o
f be
ta-h
emol
ytic
str
epto
cocc
i m
ay h
ave
cons
titut
ive
or in
duci
ble
resi
stan
ce to
clin
dam
ycin
[met
hyla
tion
of th
e 23
SrR
NA
enco
ded
by a
n er
mge
ne a
lso
refe
rred
to
as M
LSB
(mac
rolid
e,lin
cosa
mid
e, a
nd ty
pe B
str
epto
gram
in) r
esis
tanc
e] o
r may
be
resi
stan
t onl
yto
mac
rolid
es (
efflu
x m
echa
nism
enc
oded
by
a m
efge
ne).
Indu
cibl
ecl
inda
myc
in re
sist
ance
can
be
dete
cted
usi
ng a
dis
k ap
prox
imat
ion
test
by
plac
ing
a 2-
µµ g
clin
dam
ycin
di
sk
12
mm
fr
om
the
edge
of
a
15-µµ
ger
ythr
omyc
in d
isk
as p
art o
f the
nor
mal
dis
k di
ffusi
on p
roce
dure
. Fol
low
ing
incu
batio
n, o
rgan
ism
s th
at d
o no
t sho
w fl
atte
ning
of t
he c
linda
myc
in z
one
shou
ld b
e re
port
ed a
s cl
inda
myc
in s
usce
ptib
le.
Org
anis
ms
that
sho
wfla
tteni
ng o
f th
e cl
inda
myc
in z
one
adja
cent
to
the
eryt
hrom
ycin
dis
k(r
efer
red
to a
s a
“D”
zone
) ha
ve i
nduc
ible
clin
dam
ycin
res
ista
nce.
Su
chis
olat
es s
houl
d be
rep
orte
d as
“cl
inda
myc
in r
esis
tant
.”
Aco
mm
ent
that
"Thi
s is
olat
e is
pre
sum
ed t
o be
res
ista
nt b
ased
on
dete
ctio
n of
indu
cibl
ecl
inda
myc
in
resi
stan
ce.
C
linda
myc
in
may
st
ill
be
effe
ctiv
e in
so
me
patie
nts.
" m
ay b
e in
clud
ed.
STR
EPTO
GR
AM
INS
CQ
uinu
pris
tin-d
alfo
pris
tin
≤1
2≥
4(1
5) R
epor
t aga
inst
Stre
ptoc
occu
s py
ogen
es.
OXA
ZOLI
DIN
ON
ESC
Line
zolid
≤2
--
See
com
men
t (5)
.
Tabl
e 2H
. (C
ontin
ued)
Tabl
e 2H
Stre
ptoc
occu
sspp
. O
ther
Tha
nS.
pne
umon
iae
M7-
MIC
For Use With M7-A6–MIC Testing M100-S15
©Clinical and Laboratory Standards Institute. All rights reserved. 133
This page is intentionally left blank.
January 2005 Vol. 25 No. 1
134
Tabl
e 2I
Vibr
io c
hole
rae
M7-
MIC
©Clinical and Laboratory Standards Institute. All rights reserved.
Tabl
e 2I
. M
IC In
terp
retiv
e St
anda
rds
(µµg/
mL)
for
Vibr
io c
hole
rae
Test
ing
Con
ditio
ns
Med
ium
:B
roth
dilu
tion:
Cat
ion-
adju
sted
Mue
ller-
Hin
ton
brot
h (C
AM
HB
)A
gar d
ilutio
n: M
uelle
r-H
into
n ag
ar (M
HA
)In
ocul
um:
Gro
wth
met
hod
or d
irect
col
ony
susp
ensi
on, e
quiv
alen
t to
a0.
5 M
cFar
land
sta
ndar
dIn
cuba
tion:
35 °
C ±
2 de
gree
s; a
mbi
ent a
ir; 1
6 to
20
hour
s
Min
imal
QC
Rec
omm
enda
tions
(See
Tab
le 3
for a
ccep
tabl
e Q
C ra
nges
.)
Esch
eric
hia
coli
ATC
C®
2592
2
Test
/Rep
ort
Gro
upA
ntim
icro
bial
Age
ntM
IC (µµ
g/m
L)In
terp
retiv
e St
anda
rdC
omm
ents
SI
RPE
NIC
ILLI
NS
AA
mpi
cilli
n≤
816
≥32
(1)
Cla
ss re
pres
enta
tive
for a
mpi
cilli
n an
d am
oxic
illin
.TE
TRA
CYC
LIN
ESC
Tetra
cycl
ine
≤4
8≥
16(2
) Te
tracy
clin
e is
the
repr
esen
tativ
e fo
r all
tetra
cycl
ines
, and
the
resu
ltsca
n be
app
lied
to d
oxyc
yclin
e.O
Dox
ycyc
line
≤4
8≥
16FO
LATE
PAT
HW
AYIN
HIB
ITO
RS
BTr
imet
hopr
im-s
ulfa
met
hoxa
zole
≤2/
38-
≥4/
76C
Sul
fona
mid
es≤
256
-≥
512
(3) S
ulfis
oxaz
ole
can
be u
sed
to re
pres
ent a
ny o
f the
cur
rent
ly a
vaila
ble
sulfo
nam
ide
prep
arat
ions
.PH
ENIC
OLS
CC
hlor
amph
enic
ol≤
816
≥32
NO
TE:
Info
rmat
ion
in b
oldf
ace
type
is c
onsi
dere
d te
ntat
ive
for o
ne y
ear.
For Use With M7-A6–MIC Testing M100-S15
135
Tabl
e 2J
Hel
icob
acte
r pyl
ori
M7-
MIC
©Clinical and Laboratory Standards Institute. All rights reserved.
Tabl
e 2J
. M
IC In
terp
retiv
e St
anda
rds
(µµg/
mL)
for
Hel
icob
acte
r pyl
ori
Min
imal
QC
Rec
omm
enda
tions
(See
Tab
le 3
Afo
r acc
epta
ble
QC
rang
es.)
Hel
icob
acte
r pyl
ori A
TCC
®43
504
Test
/Rep
ort
Gro
upA
ntim
icro
bial
Age
ntM
IC (µµ
g/m
L)In
terp
retiv
e St
anda
rdC
omm
ents
SI
RM
AC
RO
LID
ESA
Cla
rithr
omyc
in≤
0.25
0.5
≥1.
0(1
)
Thes
e br
eakp
oint
s pr
esum
e th
at c
larit
hrom
ycin
will
be
used
in a
nFD
A-a
ppro
ved
regi
men
tha
t in
clud
es a
pro
ton-
pum
p in
hibi
tor
or a
n H
2
anta
goni
st
(thes
e tre
atm
ents
in
clud
e om
epra
zole
, la
nsop
razo
le,
orra
ntid
ine
bism
uth
citra
te).
NO
TE:I
nfor
mat
ion
in b
oldf
ace
type
is c
onsi
dere
d te
ntat
ive
for o
ne y
ear.
Test
ing
Con
ditio
ns
Med
ium
:A
gar
dilu
tion:
M
uelle
r-H
into
n ag
ar (
MH
A)
and
aged
(≥
2w
eeks
old
) she
ep b
lood
(5%
v/v
)In
ocul
um:
Asa
line
susp
ensi
on e
quiv
alen
t to
a 2.
0 M
cFar
land
sta
ndar
d(c
onta
inin
g 1
x 10
7to
1 x
108
CFU
/mL)
, to
be p
repa
red
from
a 72
-hou
r-ol
d su
bcul
ture
fro
m a
blo
od a
gar
plat
e.
The
inoc
ulum
(1 to
thre
e µL
per s
pot)
is re
plic
ated
dire
ctly
ont
o th
ean
timic
robi
al a
gent
-con
tain
ing
agar
dilu
tion
plat
es.
Incu
batio
n:35
°C
±2
degr
ees;
thr
ee d
ays;
mic
roae
robi
c at
mos
pher
epr
oduc
ed
by
a ga
s-ge
nera
ting
syst
em
suita
ble
for
cam
pylo
bact
ers.
January 2005 Vol. 25 No. 1
136
Tabl
e 2K
Pote
ntia
l Age
nts
of B
iote
rror
ism
M7-
MIC
NO
TE:I
nfor
mat
ion
in b
oldf
ace
type
is c
onsi
dere
d te
ntat
ive
for o
ne y
ear.
Tabl
e 2K
. M
IC In
terp
retiv
e St
anda
rds
(µµg/
mL)
for
Pote
ntia
l Age
nts
of B
iote
rror
ism
: Bac
illus
ant
hrac
is, Y
ersi
nia
pest
is, B
urkh
olde
ria m
alle
i, B
urkh
olde
ria p
seud
omal
lei,
and
Fran
cise
lla tu
lare
nsis
©Clinical and Laboratory Standards Institute. All rights reserved.
Org
anis
mG
roup
Ant
imic
robi
al A
gent
MIC
(µµg/
mL)
Inte
rpre
tive
Stan
dard
Com
men
ts
SI
RPE
NIC
ILLI
NS
B. a
nthr
acis
Pen
icill
in≤
0.12
-≥
0.25
(7) C
lass
repr
esen
tativ
e fo
r am
oxic
illin
.ββ -
LAC
TAM
/ββ-L
AC
TAM
ASE
INH
IBIT
OR
CO
MB
INAT
ION
SB.
pse
udom
alle
iA
mox
icill
in-c
lavu
lani
c ac
id≤
8/4
16/8
≥ 32
/16
Min
imal
QC
Rec
omm
enda
tions
(See
Tab
le 3
for a
ccep
tabl
e Q
C ra
nges
.)
Esch
eric
hia
coli
ATC
C®
259
22 (a
ll or
gani
sms)
Esch
eric
hia
coli
ATC
C®
3521
8 (fo
r am
oxic
illin
-cla
vula
nic
acid
and
B.
pseu
dom
alle
i)St
aphy
loco
ccus
aur
eus
ATC
C®
292
13 (f
orB.
ant
hrac
is a
nd F
. tul
aren
sis)
Pseu
dom
onas
aer
ugin
osa
ATC
C®
2785
3 (fo
rB. m
alle
i/pse
udom
alle
i and
F. tu
lare
nsis
)
Test
ing
Con
ditio
ns
Med
ium
:B
roth
dilu
tion:
Cat
ion-
adju
sted
Mue
ller-
Hin
ton
brot
h (C
AM
HB
); fo
r F.
tula
rens
isad
d 2%
def
ined
gro
wth
sup
plem
ent
Inoc
ulum
:G
row
th m
etho
d or
dire
ct c
olon
y su
spen
sion
in C
AM
HB
, equ
ival
ent t
o a
0.5
McF
arla
nd s
tand
ard;
for
F.
tula
rens
is p
repa
re i
nocu
lum
as
adi
rect
col
ony
susp
ensi
on fr
om a
cho
cola
te a
gar
plat
eIn
cuba
tion:
35 °
C ±
2 de
gree
s; a
mbi
ent a
ir; 1
6 to
20
hour
s;fo
r Y.
pes
tisin
cuba
te24
ho
urs
and
if un
acce
ptab
le
grow
th
in
the
cont
rol
wel
lre
incu
bate
an
addi
tiona
l 24
hour
s; fo
r F. t
ular
ensi
s in
cuba
te 4
8 ho
urs
Gen
eral
Com
men
ts
(1)
Extr
eme
Cau
tion:
Pub
lic h
ealth
offi
cial
s sh
ould
be
notif
ied
abou
t al
l is
olat
es p
resu
mpt
ivel
y id
entif
ied
as B
. an
thra
cis,
Y.
pest
is,
B. m
alle
i, or
B.ps
eudo
mal
leio
r F.
tul
aren
sis.
Con
firm
atio
n of
isol
ates
of
thes
e ba
cter
ia m
ay r
equi
re s
peci
aliz
ed t
estin
g on
ly a
vaila
ble
in r
efer
ence
or
publ
ic h
ealth
labo
rato
ries.
Rec
omm
ende
d pr
ecau
tions
: Bio
safe
ty L
evel
2 (B
SL2
) pra
ctic
es, c
onta
inm
ent e
quip
men
t, an
d fa
cilit
ies
are
reco
mm
ende
d fo
r act
iviti
es u
sing
clin
ical
mat
eria
ls a
nd d
iagn
ostic
qua
ntiti
es o
f in
fect
ious
cul
ture
s. B
iosa
fety
Lev
el 3
(B
SL3
) pr
actic
es,
cont
ainm
ent
equi
pmen
t, an
d fa
cilit
ies
are
reco
mm
ende
d fo
r wor
k in
volv
ing
prod
uctio
n qu
antit
ies
or c
once
ntra
tions
of c
ultu
res,
and
for a
ctiv
ities
with
a h
igh
pote
ntia
l for
aer
osol
pro
duct
ion.
If B
SL2
or B
SL3
faci
litie
s ar
e no
t ava
ilabl
e, is
olat
es s
houl
d be
forw
arde
d to
refe
renc
e or
pub
lic h
ealth
labo
rato
ries
for s
usce
ptib
ility
test
ing.
(2
) In
terp
retiv
e cr
iteria
are
pro
pose
d ba
sed
on p
opul
atio
n di
strib
utio
ns, p
harm
acok
inet
ics
of th
e an
timic
robi
al a
gent
s, p
revi
ousl
y pu
blis
hed
lite
ratu
re, a
ndan
imal
mod
el d
ata.
(3)
Crit
eria
forB
. ant
hrac
isdo
not
app
ly to
oth
er B
acillu
ssp
p.(4
) W
AR
NIN
G: F
or Y
. pes
tis,s
tudi
es h
ave
dem
onst
rate
d th
at a
lthou
gh β
-lact
am a
ntim
icro
bial
age
nts
may
app
ear a
ctiv
e in
vitr
o,th
ey la
ck e
ffica
cy in
ani
mal
mod
els
of in
fect
ion.
The
se a
ntim
icro
bial
age
nts
shou
ld n
ot b
e re
porte
d as
sus
cept
ible
.(5
) Th
e re
com
men
ded
med
ium
for t
estin
g F.
tula
rens
isco
nsis
ts o
f CA
MH
B to
whi
ch a
2%
def
ined
gro
wth
sup
plem
ent (
25.9
g L
-cys
tein
e H
CL,
1.1
g L-
Cys
tine,
1 g
ade
nine
, 0.0
3 g
guan
ine
HC
L, 0
.01
g Vi
tam
in B
12, 0
.1 g
coc
arbo
xyla
se, 0
.25
g N
AD
, 10
g L-
glut
amin
e, 0
.02
g fe
rric
nitr
ate,
100
g gl
ucos
e, 3
mg
thia
min
e H
CL,
13
mg
p-am
inob
enzo
ic a
cid
[in 1
LH
2O])
is a
dded
afte
r aut
ocla
ving
. The
pH
of m
ediu
m s
houl
d be
adj
uste
d to
7.2
to 7
.4.
(6)
For
som
e or
gani
sm/a
ntim
icro
bial
age
nt c
ombi
natio
ns, t
he a
bsen
ce o
f res
ista
nt s
trai
ns p
recl
udes
def
inin
g an
y re
sults
cat
egor
ies
othe
r th
an"s
usce
ptib
le."
For
str
ains
yie
ldin
g re
sults
sug
gest
ive
of a
"no
nsus
cept
ible
" ca
tego
ry, o
rgan
ism
iden
tific
atio
n an
d an
timic
robi
al s
usce
ptib
ility
test
resu
lts s
houl
d be
con
firm
ed. S
ubse
quen
tly, t
he is
olat
es s
houl
d be
sav
ed a
nd s
ubm
itted
to a
refe
renc
e la
bora
tory
that
will
con
firm
resu
ltsus
ing
a C
LSI/N
CC
LS r
efer
ence
dilu
tion
met
hod.
For Use With M7-A6–MIC Testing M100-S15
137©Clinical and Laboratory Standards Institute. All rights reserved.
Tabl
e 2K
Pote
ntia
l Age
nts
of B
iote
rror
ism
M7-
MIC
Org
anis
mG
roup
Ant
imic
robi
al A
gent
MIC
(µµg/
mL)
Inte
rpre
tive
Stan
dard
Com
men
ts
SI
RC
EPH
EMS
(PA
REN
TER
AL)
(Inc
ludi
ng c
epha
losp
orin
s I,
II, II
I, an
d IV
. Ple
ase
refe
r to
Glo
ssar
y I.)
B. m
alle
i B.
pse
udom
alle
iC
efta
zidi
me
≤8
16≥
32
CA
RB
APE
NEM
S B.
mal
lei
B. p
seud
omal
lei
Imip
enem
≤4
8≥
16
AM
INO
GLY
CO
SID
ESY.
pes
tisG
enta
mic
in≤
48
≥ 16
Stre
ptom
ycin
≤ 4
8≥
16F.
tula
rens
isG
enta
mic
in≤≤
4-
-Se
e co
mm
ent (
6).
Stre
ptom
ycin
≤≤8
--
See
com
men
t (6)
.TE
TRA
CYC
LIN
ESB.
ant
hrac
isTe
tracy
clin
e≤
1.0
--
(8)
Org
anis
ms
that
are
sus
cept
ible
to te
tracy
clin
e ar
e al
so c
onsi
dere
d su
scep
tible
todo
xycy
clin
e. H
owev
er, s
ome
orga
nism
s th
at a
re in
term
edia
te o
r res
ista
nt to
tetra
cycl
ine
may
be
susc
eptib
le to
dox
ycyc
line.
See
com
men
t (6)
. D
oxyc
yclin
e≤
1.0
--
B. m
alle
iB.
pse
udom
alle
i Y.
pes
tis
Tetra
cycl
ine
≤ 4
8≥
16S
ee c
omm
ent (
8).
Dox
ycyc
line
≤ 4
8≥
16
F. tu
lare
nsis
Tetr
acyc
line
≤≤ 4
--
See
com
men
ts (6
) and
(8).
Dox
ycyc
line
≤≤ 4
--
FLU
OR
OQ
UIN
OLO
NES
B. a
nthr
acis
Cip
roflo
xaci
n≤
0.5
--
See
com
men
t (6)
.Y.
pes
tisC
ipro
floxa
cin
≤ 1
2≥
4F.
tula
rens
isC
ipro
floxa
cin
≤≤ 0.
5-
-Se
e co
mm
ent (
6).
Levo
floxa
cin
≤≤ 0.
5-
-Se
e co
mm
ent (
6).
FOLA
TE P
ATH
WAY
INH
IBIT
OR
SB.
pse
udom
alle
iY.
pes
tisTr
imet
hopr
im-s
ulfa
met
hoxa
zole
≤ 2/
38-
≥4/
76
PHEN
ICO
LSY.
pes
tisC
hlor
amph
enic
ol≤
816
≥ 32
F. tu
lare
nsis
Chl
oram
phen
icol
≤≤ 8
--
See
com
men
t (6)
.
Tabl
e 2K
. (C
ontin
ued)
January 2005 Vol. 25 No. 1
©Clinical and Laboratory Standards Institute. All rights reserved.138
Tabl
e 2L
. MIC
Inte
rpre
tive
Stan
dard
s (µµ
g/m
L) fo
r N
eiss
eria
men
ingi
tidis
Test
ing
Con
ditio
ns
Med
ium
: B
roth
m
icro
dilu
tion:
C
atio
n-ad
just
ed
Mue
ller-
Hin
ton
brot
h(C
AM
HB
) sup
plem
ente
d w
ith 2
to 5
% ly
sed
hors
e bl
ood.
A
gar
dilu
tion:
M
uelle
r-H
into
n ag
ar
supp
lem
ente
d w
ith
5%de
fibrin
ated
she
ep b
lood
.In
ocul
um:
Dire
ct c
olon
y su
spen
sion
fro
m a
20
to 2
4 h
grow
th f
rom
Cho
cola
te a
gar
incu
bate
d at
35
°C; 5
% C
O2;
equ
ival
ent t
o a
0.5
McF
arla
nd s
tand
ard.
Col
onie
s gr
own
on s
heep
blo
od a
gar m
aybe
use
d fo
r in
ocul
um p
repa
ratio
n. H
owev
er, t
he 0
.5 M
cFar
land
susp
ensi
on
obta
ined
fr
om
shee
p bl
ood
agar
w
ill
cont
ain
appr
oxim
atel
y 50
% f
ewer
CFU
/mL.
Thi
s m
ust
be t
aken
int
oac
coun
t w
hen
prep
arin
g th
e fin
al
dilu
tion
prio
r to
pa
nel
inoc
ulat
ion,
as
guid
ed b
y co
lony
cou
nts.
Incu
batio
n:
35 °
C ±
2 de
gree
s; 5
% C
O2;
20
to 2
4 ho
urs
Tabl
e 2L
Nei
sser
ia m
enin
gitid
isM
7-M
IC
Min
imal
QC
Rec
omm
enda
tions
(See
Tab
les
3 an
d 3A
for
acce
ptab
leQ
C r
ange
s).
Stre
ptoc
occu
s pn
eum
onia
e AT
CC
®49
619
incu
bate
d ei
ther
in
ambi
ent
air
or 5
% C
O2,
exc
ept
that
azi
thro
myc
in Q
C t
ests
mus
t be
incu
bate
d in
am
bien
t air.
E.
col
iAT
CC
®25
922
(incu
bate
d ei
ther
in
ambi
ent
air
or 5
% C
O2)
shou
ld b
e us
ed f
or c
ipro
floxa
cin,
nal
idix
ic a
cid,
min
ocyc
line,
and
sulfi
soxa
zole
.
Gen
eral
Com
men
ts
(1)
Rec
omm
ende
d pr
ecau
tions
: B
iosa
fety
Lev
el 2
(B
SL2)
pra
ctic
es a
re r
ecom
men
ded
for
this
org
anis
m.
Whe
neve
r po
ssib
le,
proc
edur
es li
kely
to g
ener
ate
aero
sols
sho
uld
be p
erfo
rmed
with
in a
bio
logi
cal s
afet
y ca
bine
t.
(2)
Inte
rpre
tive
crite
ria a
re b
ased
upo
n po
pula
tion
dist
ribut
ions
of
MIC
s of
var
ious
age
nts,
pha
rmac
okin
etic
s of
the
age
nts,
prev
ious
ly p
ublis
hed
liter
atur
e, a
nd th
e cl
inic
al e
xper
ienc
e of
cer
tain
mem
bers
of t
he s
ubco
mm
ittee
. Sys
tem
atic
ally
col
lect
edcl
inic
al d
ata
wer
e no
t ava
ilabl
e to
rev
iew
with
man
y of
the
antim
icro
bial
age
nts
in th
is ta
ble.
(3)
For
som
e or
gani
sm/a
ntim
icro
bial
age
nt c
ombi
natio
ns,
the
abse
nce
of r
esis
tant
str
ains
pre
clud
es d
efin
ing
any
resu
ltsca
tego
ries
othe
r th
an “
susc
eptib
le.”
For
str
ains
yie
ldin
g re
sults
sug
gest
ive
of a
“no
nsus
cept
ible
” ca
tego
ry,
orga
nism
iden
tific
atio
n an
d an
timic
robi
al s
usce
ptib
ility
tes
t re
sults
sho
uld
be c
onfir
med
. Sub
sequ
ently
, the
isol
ates
sho
uld
be s
aved
and
subm
itted
to a
ref
eren
ce la
bora
tory
that
will
con
firm
res
ults
usi
ng a
CLS
I/NC
CLS
ref
eren
ce d
ilutio
n m
etho
d.
(4)
With
azi
thro
myc
in,
brea
kpoi
nts
wer
e de
velo
ped
initi
ally
usi
ng M
ICs
dete
rmin
ed b
y in
cuba
tion
in a
mbi
ent
air
for
the
phar
mac
odyn
amic
cal
cula
tions
.
(5)
Inst
ruct
ions
for
pre
para
tion
of l
ysed
hor
se b
lood
are
pro
vide
d in
CLS
I/NC
CLS
doc
umen
t M
7—M
etho
ds f
or D
ilutio
nA
ntim
icro
bial
Sus
cept
ibili
ty T
estin
g fo
r Bac
teria
that
Gro
w A
erob
ical
ly.
NO
TE:
Info
rmat
ion
in b
oldf
ace
type
is c
onsi
dere
d te
ntat
ive
for
one
year
.
For Use With M7-A6–MIC Testing M100-S15
©Clinical and Laboratory Standards Institute. All rights reserved. 139
Tabl
e 2L
Nei
sser
ia m
enin
gitid
isM
7-M
IC
Test
/Rep
ort
Gro
upA
ntim
icro
bial
Age
ntM
IC (µ
g/m
L)In
terp
retiv
e St
anda
rdC
omm
ents
SI
RPE
NIC
ILLI
NS
C CPe
nici
llin
Am
pici
llin
≤≤0.
06≤≤
0.12
0.12
-0.2
50.
25-1
≥≥ 0.
5≥≥
2C
EPH
EMS
(PA
REN
TER
AL)
(Inc
ludi
ng c
epha
losp
orin
s I,
II, II
I, an
d IV
. Ple
ase
refe
r to
Glo
ssar
y I.)
C CC
efot
axim
e or
ceftr
iaxo
ne≤≤
0.12
≤≤
0.12
– –
– –Se
e co
mm
ent (
3).
CA
RB
APE
NEM
SC
Mer
open
em≤≤
0.25
––
See
com
men
t (3)
.M
AC
RO
LID
ESC
Azi
thro
myc
in≤≤
2 –
–Se
e co
mm
ents
(3) a
nd (4
).(6
) May
be
appr
opria
te o
nly
for
prop
hyla
xis
of m
enin
goco
ccal
cas
e co
ntac
ts. T
hese
brea
kpoi
nts
do n
ot a
pply
to
ther
apy
of p
atie
nts
with
inv
asiv
e m
enin
goco
ccal
dise
ase.
TETR
AC
YCLI
NES
CM
inoc
yclin
e≤≤
2 –
–Se
e co
mm
ents
(3) a
nd (6
).
FLU
OR
OQ
UIN
OLO
NES
C CC
ipro
floxa
cin
Levo
floxa
cin
≤≤0.
03≤≤
0.03
0.06
0.06
≥≥0.
12
≥≥0.
12
See
com
men
t (6)
.(7
) Fo
r su
rvei
llanc
e pu
rpos
es,
a na
lidix
ic a
cid
MIC
≥≥8
µg/m
Lm
ay c
orre
late
with
dim
inis
hed
fluor
oqui
nolo
ne s
usce
ptib
ility
.FO
LATE
PAT
HW
AYIN
HIB
ITO
RS
C CSu
lfiso
xazo
leTr
imet
hopr
im-
sulfa
met
hoxa
zole
≤≤2
≤≤0.
12/2
.34 0.
25/4
.75
≥≥8
≥≥0.
5/9.
5 Se
e co
mm
ent (
6).
PHEN
ICO
LS CC
hlor
amph
enic
ol≤≤
2 4
≥≥8
AN
SAM
YCIN
SC
Rifa
mpi
n≤≤
0.5
1≥≥
2Se
e co
mm
ent (
6).
Tabl
e 2L
. (C
ontin
ued)
140
Tabl
e 3
Non
fast
idio
us Q
ualit
y C
ontro
lM
7-M
IC
©Clinical and Laboratory Standards Institute. All rights reserved.
January 2005 Vol. 25 No. 1Table 3. Acceptable Limits for Quality Control Strains Used to Monitor Accuracy of MinimalInhibitory Concentrations (MICs) (µµg/mL) of Nonfastidious Organisms (Using Cation-AdjustedMueller-Hinton Medium Without Blood or Other Nutritional Supplements)
Antimicrobial Agent
Staphylococcusaureus
ATCC® 29213a
Enterococcusfaecalis
ATCC® 29212
Escherichiacoli
ATCC® 25922
Pseudomonasaeruginosa
ATCC® 27853
Escherichiacoli
ATCC® 35218b
AmikacinAmoxicillin-clavulanic acidAmpicillinAmpicillin-sulbactamAzithromycinAzlocillinAztreonamCarbenicillinCefaclorCefamandoleCefazolinCefdinirCefditorenCefepimeCefetametCefiximeCefmetazoleCefonicidCefoperazoneCefotaximeCefotetanCefoxitinCefpodoximeCefprozilCeftazidimeCeftibutenCeftizoximeCeftriaxoneCefuroximeCephalothinChloramphenicolCinoxacinCiprofloxacinClarithromycinClinafloxacinClindamycinc
ColistinDalbavancinDaptomycind
DirithromycinDoripenemDoxycyclineEnoxacinErtapenemErythromycinc
FleroxacinFosfomycine
GarenoxacinGatifloxacinGemifloxacinGentamicinf
GrepafloxacinImipenemKanamycinLevofloxacinLinezolidLomefloxacin
1-40.12/0.06-0.5/0.25
0.5-2-
0.5-22-8
-2-81-4
0.25-10.25-1
0.12-0.50.25-2
1-4-
8-320.5-21-41-41-4
4-161-41-8
0.25-14-16
-2-81-8
0.5-20.12-0.5
2-16-
0.12-0.50.12-0.5
0.008-0.060.06-0.25
-0.03-0.12
0.25-11-4
0.015-0.060.12-0.5
0.5-20.06-0.25
0.25-10.25-10.5-4
0.004-0.030.03-0.12
0.008-0.030.12-1
0.03-0.120.015-0.06
1-40.06-0.5
1-40.25-2
64-2560.25/0.12-1.0/0.5
0.5-2--
1-4-
16-64----------------------
4-16-
0.25-2-
0.03-0.254-16
-0.03-0.12
1-4-
1-42-8
2-164-161-42-8
32-1280.03-0.250.12-1.0
0.015-0.124-16
0.12-0.50.5-216-640.25-2
1-42-8
0.5-42/1-8/4
2-82/1-8/4
-8-32
0.06-0.254-161-4
0.25-11-4
0.12-0.50.12-1
0.015-0.120.25-10.25-10.25-10.25-1
0.12-0.50.03-0.120.06-0.25
2-80.25-1
1-40.06-0.50.12-0.5
0.03-0.120.03-0.12
2-84-162-82-8
0.004-0.015-
0.002-0.015-
0.25-1---
0.015-0.060.5-2
0.06-0.250.004-0.015
-0.03-0.12
0.5-20.004-0.030.008-0.03
0.004-0.0150.25-1
0.004-0.030.06-0.25
1-40.008-0.06
-0.03-0.12
1-4----
2-82-8
16-64-----
1-8--
> 32-
2-88-32
----
1-4-
16-648-64
----
0.25-1-
0.06-0.5-
0.25-2---
0.12-0.5-
2-82-8
-1-42-8
0.5-20.5-2
0.25-10.5-2
0.25-2.01-4
-0.5-4
-1-4
-4/2-16/8
-8/4-32/16
-----------------------------------------------------
141©Clinical and Laboratory Standards Institute. All rights reserved.
For Use With M7-A6–MIC Testing M100-S15
NOTE 1: These MICs were obtained in several reference laboratories by broth microdilution. If four or fewerconcentrations are tested, quality control may be more difficult.
NOTE 2: Information in boldface type is considered tentative for one year.NOTE 3: For four-dilution ranges, results at the extremes of the acceptable range(s) should be suspect. Verify control
validity with data from other control strains.
Footnotesa. ATCC is a registered trademark of the American Type Culture Collection.b. Because this strain may lose its plasmid, careful organism maintenance is required; refer to M7, Section 12.4. c. When disk approximation tests are performed with erythromycin and clindamycin, S. aureus ATCC® BAA-977
(containing inducible ermA-mediated resistance) and S. aureus ATCC® BAA-976 (containing msrA-mediated macrolide-only efflux) are recommended for quality assessment purposes (e.g., training, competency assessment, or testevaluation). S. aureus ATCC® BAA-977 should demonstrate inducible clindamycin resistance (i.e., a positive D-zonetest), while S. aureus ATCC® BAA-976 should not demonstrate inducible clindamycin resistance. S. aureus ATCC®25923 should be used for routine quality control (e.g., weekly or daily) of erythromycin and clindamycin disks usingstandard Mueller-Hinton agar.
d. QC ranges reflect MICs obtained when Mueller-Hinton broth is supplemented with calcium to a final concentration of50 µg/mL.
e. The approved MIC susceptibility testing method is agar dilution. Agar media should be supplemented with 25 µg/mL ofglucose-6-phosphate. Broth dilution should not be performed.
f. For control organisms for gentamicin and streptomycin high-level aminoglycoside screen tests for enterococci, see Table2D.
g. This test should be performed by agar dilution only.h. Very medium-dependent, especially with enterococci.i. The quality control limits for E. coli ATCC® 35218 when using Haemophilus Test Medium (HTM) are 16/2 to 64/2 µg/mL.j. For broth microdilution testing of tigecycline, when MIC panels are prepared, the medium must be prepared
fresh on the day of use. The medium must be no greater than 12 hours old at the time the panels are made,however, the panels may then be frozen for later use.
k. For control organisms for vancomycin screen test for enterococci, see Table 2D.
Table 3. (Continued)
Tabl
e 3
Non
fast
idio
us Q
ualit
y C
ontro
lM
7-M
IC
Antimicrobial Agent
Staphylococcusaureus
ATCC® 29213a
Enterococcusfaecalis
ATCC® 29212
Escherichiacoli
ATCC® 25922
Pseudomonasaeruginosa
ATCC® 27853
Escherichiacoli
ATCC® 35218b
LoracarbefMecillinamMeropenemMethicillinMezlocillinMinocyclineMoxalactamMoxifloxacinNafcillinNalidixic acidNetilmicinNitrofurantoinNorfloxacinOfloxacinOritavancinOxacillinPenicillinPiperacillinPiperacillin-tazobactamPolymyxin BQuinupristin-dalfopristinRifampinSparfloxacinSulfisoxazoleh
TeicoplaninTelavancinTelithromycinTetracyclineTicarcillinTicarcillin-clavulanic acidTigecycline j
TobramycinTrimethoprimh
Trimethoprim-sulfamethoxazoleTrospectomycinTrovafloxacinVancomycink
0.5-2-
0.03-0.120.5-21-4
0.06-0.54-16
0.015-0.120.12-0.5
-≤ 0.258-320.5-2
0.12-10.5-2
0.12-0.50.25-2
1-40.25/4-2/4
-0.25-1
0.004-0.0150.03-0.1232-1280.25-10.12-1
0.06-0.250.12-1
2-80.5/2-2/20.03-0.25
0.12-11-4
≤ 0.5/9.52-16
0.008-0.030.5-2
--
2-8>161-41-4
-0.06-0.5
2-8-
4-164-162-81-4
0.12-18-321-41-4
1/4-4/4-
2-80.5-4
0.12-0.532-128
0.06-0.250.12-0.5
0.015-0.128-32
16-6416/2-64/20.03-0.12
8-32≤ 1
≤ 0.5/9.52-8
0.06-0.251-4
0.5-20.03-0.25f
0.008-0.06-
2-80.25-1
0.12-0.50.008-0.06
-1-4
≤ 0.5-14-16
0.03-0.120.015-0.12
---
1-41/4-4/40.25-2
-4-16
0.004-0.0158-32
---
0.5-24-16
4/2-16/20.03-0.25
0.25-10.5-2
≤ 0.5/9.58-32
0.004-0.015-
>8-
0.25-1-
8-32-
8-321-8
--
0.5-8-
1-41-8
---
1-81/4-8/40.25-2
-16-640.5-2
----
8-328-32
8/2-32/2-
0.25-1>64
8/152-32/608-
0.25-2-
------------------
0.5/4-2/4----------
8/2-32/2i
-------
January 2005 Vol. 25 No. 1
142
Tabl
e 3A
Fast
idio
us Q
ualit
y C
ontro
lM
7-M
IC
©Clinical and Laboratory Standards Institute. All rights reserved.
Table 3A. Acceptable Limits for Quality Control Strains Used to Monitor Accuracy of MinimalInhibitory Concentrations (MICs) (µg/mL) of Fastidious Organisms
Antimicrobial Agent
Haemophilusinfluenzae
ATCC® 49247a
Haemophilusinfluenzae
ATCC®
49766
Neisseria gonorrhoeaeATCC® 49226
Streptococcuspneumoniae
ATCC® 49619
Helicobacterpylori
ATCC® 43504
Campylobacterjejuni
ATCC® 33560b
36 °C/48 hours
Campylobacterjejuni
ATCC® 33560b
42 °C/24 hours
Amoxicillinc
Amoxicillin-clavulanic acidc
Ampicillin Ampicillin-
sulbactamAzithromycin Aztreonam CefaclorCefamandoleCefdinirCefditorenCefepimeCefetametCefiximeCefmetazoleCefonicidCefotaximeCefotetanCefoxitinCefpiromeCefpodoxime Cefprozil Ceftazidime Ceftibuten Ceftizoxime Ceftriaxone Cefuroxime Cephalothin ChloramphenicolCiprofloxacin Clarithromycin ClinafloxacinClindamycinDalbavancinDaptomycind
DirithromycinDoripenemDoxycyclineEnoxacin ErtapenemErythromycinFleroxacinGarenoxacinGatifloxacinGemifloxacinGentamicinGrepafloxacinImipenemLevofloxacinLinezolidLomefloxacinLoracarbefMeropenemMetronidazoleMoxifloxacinNitrofurantoin
- 2/1-16/8
2-82/1-8/4
1-40.12-0.5
---
0.06-0.250.5-20.5-20.12-12-16
-0.12-0.5
--
0.25-10.25-1
- 0.12-1 0.25-1
0.06-0.5 0.06-0.25
- -
0.25-1 0.004-0.03
4-160.001-0.008
---
8-32-----
0.03-0.120.002-0.0080.004-0.030.002-0.008
-0.002-0.015
-0.008-0.03
-0.03-0.12
---
0.008-0.03-
--
--
--
1-40.25-1
0.12-0.5-----
0.06-0.25-----
1-4 ----
0.25-1 ---------
0.06-0.25--
0.015-0.06 -------
0.25-1---
0.5-20.03-0.12
---
--
--
--- -
0.008-0.03-
0.015-0.060.015-0.250.004-0.03
0.5-2-
0.015-0.060.5-20.5-2
-0.03-0.12
- 0.03-0.12
- 0.008-0.03 0.004-0.015
0.25-1 - -
0.001-0.008--------
0.015-0.06- -
0.008-0.03-
0.002-0.015--
0.004-0.03---
0.008-0.03-----
0.03-0.120.03/0.015 -
0.12/0.060.06-0.25
-
0.06-0.25-
1-4-
0.03-0.250.015-0.120.03-0.25
0.5-2---
0.03-0.12---
0.03-0.12 0.25-1
- -
0.12-0.50.03-0.12
0.25-1 0.5-2 2-8
- 0.03-0.120.03-0.120.03-0.120.008-0.030.06-0.50.06-0.250.03-0.120.015-0.12
-0.03-0.25 0.03-0.12
-0.015-0.060.12-0.5
0.008-0.03-
0.06-0.50.03-0.12
0.5-20.5-2
-2-8
0.06-0.25-
0.06-0.254-16
0.015-0.12-
- -
- - - - - - - - - - - - - - - - - - - - - - - - -
0.015-0.12--------- -------------
64-256--
- -
- -
- - - - ----------- -- - - - - - - -
0.12-1-------
0.5-2--
1-8----
0.5-2------
0.004-0.015---
- -
- -
- - - - - - - - - - - - - -- - - - - - - - - -
0.06-0.5 -------
0.25-2--
1-4----
0.5-4------
0.008-0.03---
For Use With M7-A6–MIC Testing M100-S15
Tabl
e 3A
Fast
idio
us Q
ualit
y C
ontro
lM
7-M
IC
Table 3A. (Continued)
Organism Haemophilusinfluenzae Neisseria gonorrhoeae Streptococcus
pneumoniaeHelicobacter
pyloriCampylobacter
spp.
Medium
Broth dilution:HaemophilusTest Medium(HTM) broth
Agar dilution: GC agar baseand 1% defined growthsupplement. The use of acysteine-free supplement isrequired for agar dilutiontests with carbapenems andclavulanate. Cysteine-containing defined growthsupplements do notsignificantly alter dilution testresults with other drugs.
Broth dilution: Cation-adjusted Mueller-Hinton broth with lysedhorse blood (2-5% v/v).
Agar Dilution:Mueller-Hintonagar with aged(≥ 2-week-old)sheep blood (5%v/v).
Agar dilution:Mueller-Hintonagar with 5%defibrinatedsheep blood
Inoculum Direct colonysuspension,equivalent to a0.5 McFarlandstandard
Direct colony suspension,equivalent to a 0.5McFarland standard
Direct colonysuspension, equivalentto a 0.5 McFarlandstandard
See footnote f,below.
Direct colonysuspension,equivalent to a0.5 McFarlandstandard
IncubationCharacteristics
35 °C; ambientair; 20-24 hours
35 °C; 5% CO2; 20-24 hours 35 °C; ambient air; 20-24 hours
35 °C; three days;microaerobicatmosphereproduced by gas-generating systemsuitable forcampylobacters
36 °C /48 hoursor 42 °C/ 24hours; 10% CO2,5% O2 and 85%N2 or amicroaerophilicenvironment
Testing Conditions for Clinical Isolates and Performance of Quality Control
NOTE 1: Information in boldface type is considered tentative for one year.NOTE 2: For four-dilution ranges, results at the extremes of the acceptable range(s) should be suspect. Verify control validity
with data from other control strains.Footnotes
a. ATCC is a registered trademark of the American Type Culture Collection.b. Since some isolates of C. jejuni ssp. doylei, C. fetus, and C. lari may not grow at 42 °C, susceptibility testing of these isolates
should be performed at 36 °C.c. Quality control limits for E. coli ATCC® 35218 when tested on HTM are 4/2 to 16/8 µg/mL for amoxicillin-clavulanic acid and
≥ 256 µg/mL for amoxicillin; testing amoxicillin may help to determine if the isolate has maintained its ability to produce β-lactamase.
d. QC ranges reflect MICs obtained when Mueller-Hinton broth is supplemented with calcium to a final concentration of 50 µg/mL.e. For broth microdilution testing of tigecycline, when MIC panels are prepared, the medium must be prepared fresh on
the day of use. The medium must be no greater than 12 hours old at the time the panels are made, however, the panelsmay then be frozen for later use.
f. The inoculum for testing of H. pylori should be as follows: a saline suspension equivalent to a 2.0 McFarland standard(containing 1x107 to 1x108 CFU/mL), to be prepared from a 72-hour-old subculture from a blood agar plate. The inoculum (1to 3 µL per spot) is replicated directly on the antimicrobial agent-containing agar dilution plates.
143©Clinical and Laboratory Standards Institute. All rights reserved.
Antimicrobial Agent
Haemophilusinfluenzae
ATCC® 49247a
Haemophilusinfluenzae
ATCC® 49766
Neisseria gonorrhoeaeATCC® 49226
StreptococcuspneumoniaeATCC® 49619
HelicobacterpyloriATCC®
43504
Campylobacterjejuni
ATCC® 33560b
36 °C/48 hours
Campylobacterjejuni
ATCC® 33560b
42 °C/24 hours
NorfloxacinOfloxacinOritavancinPenicillinPiperacillin-tazobactamQuinupristin-
dalfopristinRifampinSparfloxacinSpectinomycinTelavancinTelithromycinTetracyclineTigecycline
e
Trimethoprim-sulfamethoxazole
TrospectomycinTrovafloxacinVancomycin
-0.015-0.06
--
0.06/4-0.5/42-8
0.25-10.004-0.015
--
1-44-32
0.06-0.50.03/0.59-0.25/4.75
0.5-20.004-0.015
-
------
--------
---
-0.004-0.015
-0.25-1
--
- 0.004-0.015
8-32--
0.25-1--
1-40.004-0.015
-
2-8 1-4
0.008-0.060.25-1
-0.25-1
0.015-0.060.12-0.5
- 0.002-0.0150.004-0.03
0.12-0.50.015-0.120.12/2.4-
1/191-4
0.06-0.250.12-0.5
------
----
0.06-0.50.12-1.0
--
---
------
--------
---
------
--------
---
January 2005 Vol. 25 No. 1
©Clinical and Laboratory Standards Institute. All rights reserved.144
Table 3B. Acceptable Limits for Quality Control Strains Used to Monitor Accuracy of MinimalInhibitory Concentrations (MICs) (µµg/mL) Generated in Cation-Adjusted Mueller-Hinton Broth + 2%Defined Growth Supplement
AntimicrobialAgent
Staphylococcus aureus
ATCC® 29213 24 hours
Staphylococcus aureus
ATCC® 29213 48 hours
Escherichia coli
ATCC® 2592224 hours
Escherichia coli
ATCC® 2592248 hours
Pseudomonasaeruginosa
ATCC® 2785324 hours
Pseudomonasaeruginosa
ATCC® 2785348 hours
CiprofloxacinChloramphenicolDoxycyclineGentamicinLevofloxacinNalidixic AcidStreptomycinTetracyclineTrimethoprim-
sulfamethoxazole
0.25-14-16
0.12-10.25-1
0.12-0.5—
8-320.25-2
≤≤0.25/4.75
0.25-14-32
0.25-20.25-1
0.12-0.5—
8-640.5-4
≤≤0.25/4.75
0.004-0.0162-81-4
0.25-20.008-0.03
1-88-321-4
≤≤0.5/9.5
0.004-0.034-161-8
0.25-20.008-0.06
2-88-322-8
≤≤0.5/9.5
0.12-1—
4-320.5-20.5-2
—32-128
8-32—
0.25-1 —
4-32 0.5-4 0.5-4
—32-256
8-64 —
Note 1: Francisella tularensis MIC results read after 24 hours of incubation should use 24-hour QC ranges;results read after 48 hours should use only the 48-hour QC ranges.
Tabl
e 3B
QC
Mon
itorin
g fo
r CA
MH
B+
2% D
efin
ed G
row
th S
uppl
emen
tM
7-M
IC
For Use With M7-A6–MIC Testing M100-S15Table 3C. Reference Guide to Quality Control Testing Frequency
This table summarizes the suggested frequency of testing CLSI/NCCLS-recommended ATCC qualitycontrol strains to be performed by the user of antimicrobial susceptibility tests (AST). It applies only toantimicrobial agents for which 20 or 30 consecutive test days of quality control testing producedsatisfactory results.
Number of days of consecutiveQC testing required
a
Test Modification 1 5 20 or 30 CommentsMIC Test(s)
Use new shipment or lot number X
Expand dilution range X Example:Convert from breakpoint to expandedrange MIC panels.
Reduce dilution range X Example:Convert from expanded dilution rangeto breakpoint panels.
Use new method (same company) X Examples:Convert from visual to instrument reading of panel.
Convert from overnight to rapid MICtest.
In addition, perform in-house validationstudies.
Use new manufacturer of MIC test X In addition, perform in-house validationstudies.
Inoculum PreparationConvert inoculum preparation/standardization to use of a device thathas its own QC protocol
X Example:Convert from visual adjustment of turbidity to use of a photometric devicefor which a quality control procedure isprovided.
Convert inoculum preparation/standardization to a method that isdependent on user technique
X Example:Convert from visual adjustment of turbidity to another method that is notbased on a photometric device.
Instrument/SoftwareSoftware update that affects AST results X Monitor all drugs, not just those
implicated in software modification.Repair of instrument that affects ASTresults
X Depending on extent of repair (e.g.,critical component such as the optics),additional testing may be appropriate(e.g., five days).
Tabl
e 3C
QC
Tes
ting
Freq
uenc
yM
7-M
ICNOTE 1: Addition of any NEW antimicrobial agent requires 20 or 30 consecutive days of satisfactory testing (see M7-A6, Section 12.7)
prior to use of this guide.
NOTE 2: QC can be performed prior to or concurrent with testing patient isolates. Patient results can be reported for that day if quality control results are within the acceptable limits.
NOTE 3: Manufacturers of commercial or in-house prepared tests should follow their own internal procedures and applicable regulations.
NOTE 4: Acceptable MIC QC limits for FDA-cleared antimicrobial susceptibility tests may differ slightly from acceptableCLSI/NCCLS QC limits. Users of each device should utilize manufacturer’s procedures and QC limits as indicated in theinstructions for use.
NOTE 5: For troubleshooting out-of-range results, refer to M7-A6, Section 12.9.
NOTE 6: Broth, saline, and/or water used to prepare an inoculum does not require routine quality control.
Footnote
a. Does not eliminate the need for routine weekly or daily QC testing.©Clinical and Laboratory Standards Institute. All rights reserved. 145
146
Tabl
e 4
Solv
ents
and
Dilu
ents
M7-
MIC
©Clinical and Laboratory Standards Institute. All rights reserved.
January 2005 Vol. 25 No. 1Table 4. Solvents and Diluents for Preparation of Stock Solutions of Antimicrobial Agents
Antimicrobial Agent Solvent DiluentAmikacin WaterAmoxicillin Phosphate buffer, pH 6.0, 0.1 mol/L Phosphate buffer, pH 6.0, 0.1 mol/LAmpicillin Phosphate buffer, pH 8.0, 0.1 mol/L Phosphate buffer, pH 6.0, 0.1 mol/LAzithromycin 95% ethanol or glacial acetic acidf Broth mediaAzlocillin WaterAztreonam Saturated solution sodium bicarbonate WaterCarbenicillin WaterCefaclor WaterCefadroxil Phosphate buffer, pH 6.0, 0.1 mol/L WaterCefamandole WaterCefazolin Phosphate buffer, pH 6.0, 0.1 mol/L Phosphate buffer, pH 6.0, 0.1 mol/LCefdinir Phosphate buffer, pH 6.0, 0.1 mol/L WaterCefditoren Phosphate buffer, pH 6.0, 0.1 mol/L WaterCefepime Phosphate buffer, pH 6.0, 0.1 mol/L Phosphate buffer, pH 6.0, 0.1 mol/LCefetamet Phosphate buffer, pH 6.0, 0.1 mol/L WaterCefixime Phosphate buffer, pH 7.0, 0.1 mol/L Phosphate buffer, pH 7.0, 0.1 mol/LCefmetazole WaterCefonicid WaterCefoperazone WaterCefotetan Dimethyl sulfoxidee WaterCefotaxime WaterCefoxitin WaterCefpodoxime 0.10% (11.9 mmol/L) aqueous sodium bicarbonate WaterCefprozil WaterCeftazidime Sodium carbonated WaterCeftibuten 1/10 vol DMSO WaterCeftizoxime WaterCeftriaxone WaterCefuroxime Phosphate buffer, pH 6.0, 0.1 mol/L Phosphate buffer, pH 6.0, 0.1 mol/LCephalexin Phosphate buffer, pH 6.0, 0.1 mol/L WaterCephalothin Phosphate buffer, pH 6.0, 0.1 mol/L WaterCephapirin Phosphate buffer, pH 6.0, 0.1 mol/L WaterCephradine Phosphate buffer, pH 6.0, 0.1 mol/L WaterChloramphenicol 95% ethanol WaterCinoxacin 1/2 volume of water, then add 1 mol/L NaOH, Water
dropwise to dissolveCiprofloxacin WaterClarithromycin Methanole or glacial acetic acidf Phosphate buffer, pH 6.5, 0.1 mol/LClavulanic acid Phosphate buffer, pH 6.0, 0.1 mol/L Phosphate buffer, pH 6.0, 0.1 mol/LClinafloxacin WaterClindamycin WaterColistin
aWater Water
Dalbavancin DMSO WaterDaptomycin Water Water
147
Tabl
e 4
Solv
ents
and
Dilu
ents
M7-
MIC
©Clinical and Laboratory Standards Institute. All rights reserved.
For Use With M7-A6–MIC Testing M100-S15Table 4. (Continued)
Antimicrobial Agent Solvent DiluentDirithromycin Glacial acetic acidf WaterDoripenem 0.85% physiological saline 0.85% physiological salineDoxycycline WaterEnoxacin 1/2 volume of water, then 0.1 mol/L NaOH dropwise Water
to dissolveErtapenem Phosphate buffer, pH 7.2, 0.01 mol/L Phosphate buffer, pH 7.2, 0.01 mol/LErythromycin 95% ethanol or glacial acetic acidf WaterFleroxacin 1/2 volume of water, then 0.1 mol/L NaOH dropwise Water
to dissolveGarenoxacin Water (with stirring)Gatifloxacin Water (with stirring)Gemifloxacin WaterGentamicin WaterImipenem Phosphate buffer, pH 7.2, 0.01 mol/L Phosphate buffer, pH 7.2, 0.01 mol/LKanamycin WaterLevofloxacin 1/2 volume of water, then 0.1 mol/L NaOH dropwise Water
to dissolveLinezolid WaterLomefloxacinLoracarbef WaterMecillinam WaterMeropenem WaterMethicillin WaterMetronidazole Dimethyl sulfoxidee WaterMezlocillin WaterMinocycline WaterMoxalactam 0.04 mol/L HCl (let sit for 1.5 to 2 h) Phosphate buffer, pH 6.0, 0.1 mol/L
(diammonium salt)b
Moxifloxacin WaterNafcillin WaterNalidixic acid 1/2 volume of water, then add 1 mol/L NaOH,
dropwise to dissolveNetilmicin WaterNitrofurantoinc Phosphate buffer, pH 8.0, 0.1 mol/L Phosphate buffer, pH 8.0, 0.1 mol/LNorfloxacin 1/2 volume of water, then 0.1 mol/L NaOH dropwise Water
to dissolveOfloxacin 1/2 volume of water, then 0.1 mol/L NaOH dropwise Water
to dissolveOxacillin WaterPenicillin WaterPiperacillin WaterPolymyxin B Water WaterQuinupristin-dalfopristin WaterRifampin Methanole [maximum concentration = 640 µg/mL] Water (with stirring)Sparfloxacin WaterSpectinomycin WaterStreptomycin Water
Sulbactam Water
148
Tabl
e 4
Solv
ents
and
Dilu
ents
M7-
MIC
©Clinical and Laboratory Standards Institute. All rights reserved.
January 2005 Vol. 25 No. 1
Footnotes
a. The formulation of colistin used in antimicrobial susceptibility tests is colistin sulfate and notcolistin methane sulfonate (sulfomethate).
b. The diammonium salt of moxalactam is very stable, but it is almost pure R isomer. Moxalactam for clinicaluse is a 1:1 mixture of R and S isomers. Therefore, the salt is dissolved in 0.04 mol/L HCl and allowed toreact for 1.5 to 2 hours to convert it to equal parts of both isomers.
c. Alternatively, nitrofurantoin is dissolved in dimethyl sulfoxide.
d. Anhydrous sodium carbonate is used at a weight of exactly 10% of the ceftazidime to be used. The sodiumcarbonate is dissolved in solution in most of the required water. The antibiotic is dissolved in this sodiumcarbonate solution, and water is added to the desired volume. The solution is to be used as soon aspossible, but it can be stored up to six hours at no more than 25 °C.
e. These compounds are potentially toxic. Consult the material safety data sheets (MSDS) available from theproduct manufacturer before using any of these materials.
f. For glacial acetic acid, use 1/2 volume of water, then add glacial acetic acid dropwise until dissolved, notto exceed 2.5 µL/mL.
Antimicrobial Agent Solvent DiluentSulfonamides 1/2 volume hot water and minimal amount of Water
2.5 mol/L NaOH to dissolveTazobactam WaterTelavancin DMSO WaterTelithromycin Glacial acetic acidf Water Tetracycline WaterTicarcillin Phosphate buffer, pH 6.0, 0.1 mol/L Phosphate buffer, pH 6.0, 0.1 mol/LTigecycline Water WaterTobramycin WaterTrimethoprim 0.05 mol/L lactice or hydrochlorice acid, Water (may require heat)
10% of final volumeTrimethoprim (if lactate) WaterTrospectomycin Water
Vancomycin WaterNOTE: Information in boldface type is considered tentative for one year.
Table 4. (Continued)
149
Tabl
e 5
Dilu
tion
Sche
me
for
Aga
r Dilu
tion
Tests
M7-
MIC
©Clinical and Laboratory Standards Institute. All rights reserved.
For Use With M7-A6–MIC Testing M100-S15
Table 5. Scheme for Preparing Dilutions of Antimicrobial Agents to Be Used in Agar DilutionSusceptibility Tests
Antimicrobial Solution
Step Conc. Source Vol. Diluent Intermediate Final Conc. Log2 Concentration at 1:10 Dilution in(µµg/mL) Agar (µµg/L)
5120 Stock - - 5120 512 9µg/mL(mg/L)
1 5120 Stock 2 mL 2mL 2560 256 82 5120 Stock 1 3 1280 128 73 5120 Stock 1 7 640 64 64 640 Step 3 2 2 320 32 55 640 Step 3 1 3 160 16 46 640 Step 3 1 7 80 8 37 80 Step 6 2 2 40 4 28 80 Step 6 1 3 20 2 19 80 Step 6 1 7 10 1 010 10 Step 9 2 2 5 0.5 -111 10 Step 9 1 3 2.5 0.25 -212 10 Step 9 1 7 1.25 0.125 -3
NOTE: This table is modified from Ericsson HM, Sherris JC. Antibiotic sensitivity testing. Report of an internationalcollaborative study. Acta Pathol Microbiol Scand. 1971;217 (suppl B):1-98.
150
Tabl
e 6
Dilu
tion
Sche
me
for
Bro
th D
ilutio
n Te
stsM
7-M
IC
©Clinical and Laboratory Standards Institute. All rights reserved.
January 2005 Vol. 25 No. 1Table 6. Scheme for Preparing Dilutions of Antimicrobial Agents to Be Used in Broth DilutionSusceptibility Tests
Antimicrobial Solution
NOTE: This table is modified from Ericsson HM, Sherris JC. Antibiotic sensitivity testing. Report of an internationalcollaborative study. Acta Pathol Microbiol Scand. 1971;217 (suppl B):1-90.
Footnotes
a. The volumes selected can be any multiple of these figures, depending on the number of tests to be performed.
b. CAMHB, cation-adjusted Mueller-Hinton broth. Adjustment with cations, if necessary, occurs before this step.
1 5120 µg/mL Stock 1 mL 9 mL 512 µg/mL 9
2
3
4
512
512
512
Step 1
Step 1
Step 1
1
1
1
1
3
7
256
128
64
8
7
65
6
7
64
64
64
Step 4
Step 4
Step 4
1
1
1
1
3
7
32
16
8
5
4
38
9
10
8
8
8
Step 7
Step 7
Step 7
1
1
1
1
3
7
4
2
1
2
1
0
11
12
13
1
1
1
Step 10
Step 10
Step 10
1
1
1
1
3
7
0.5
0.25
0.125
-1
-2
-3
CAMHBb FinalStep Concentration Source Volumea + Volumea = Concentration Log2
151
Tabl
e 7
Mod
ifica
tions
for L
ister
iasp
p.M
7-M
IC
©Clinical and Laboratory Standards Institute. All rights reserved.
For Use With M7-A6–MIC Testing M100-S15
CAMHB: cation-adjusted Mueller-Hinton brothLHB: lysed horse blood
Footnotes
a. WARNING: For Listeria spp., cephems may appear active in vitro but are not effective clinically and should not bereported as susceptible.
b. For some organism/antimicrobial combinations, the absence of resistant strains precludes defining any resultscategories other than “susceptible.” For strains yielding results suggestive of a “nonsusceptible” category, organismidentification and antimicrobial susceptibility test results should be confirmed. Subsequently, the isolates should besaved and submitted to a reference laboratory that will confirm results using a CLSI/NCCLS reference dilutionmethod.
NOTE 1: To prepare lysed horse blood (LHB), freeze-thaw until the blood is thoroughly lysed. Aseptically mix equalvolumes of LHB and sterile distilled water (now 50%). To be used in the broth test, the combination of brothand LHB must be clear, and this can be accomplished by centrifuging the 50% blood at 12 000 x g for 20minutes. Decant the supernatant; recentrifuge if necessary. Add appropriate amounts of the 50% LHB to thebroth medium to yield a final concentration of 2 to 5% LHB.
NOTE 2: Information in boldface type is considered tentative for one year.
Table 7. Suggested Modifications of Standard Methods for Susceptibility Testing of Listeria spp.
Organism Method Medium Incubation Comments
Listeria spp.a Brothmicrodilution
CAMHB +LHB (2-5% v/v)
35 ºC; 16-20hours
ampicillinb
≤ 2 µg/mL = susceptible
penicillinb
≤ 2 µg/mL = susceptible
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a Category I When results listed in this category are observed on individual patient isolates, they should be verified by one or moreof the following:
1. Ensuring the unusual results are not due to transcription errors, contamination, or use of a defective panel,plate, or card.
2. Checking previous reports on the patient to determine if the isolate was encountered and verified earlier.3. Confirming the identification of the isolate.4. Repeating the susceptibility test to confirm results. Sometimes it is helpful to use an alternative test method
for the repeat test. 5. For isolates that show results other than susceptible for those antimicrobial agents for which only susceptible
interpretive criteria are provided in Tables 2A to 2J (listed with an “NS” above) and for staphylococci withvancomycin-intermediate or vancomycin-resistant results: 1) confirm the organism identification; 2) confirmthe antimicrobial susceptibility test results; 3) save the isolate; and 4) submit the isolate to a referencelaboratory that will test it by a CLSI/NCCLS reference dilution method.
b Category II When results listed in this category are observed on individual patient isolates, the verification steps as outlined forCategory I should be considered if the resistance is uncommon in a given institution.
c For these antimicrobial agent/organism combinations, resistance has not been documented to date.d When submitting reports to a public health laboratory, include antimicrobial susceptibility results forSalmonella spp. that are intermediate or resistant to 3rd-generation cephalosporins and/or intermediate orresistant to fluoroquinolone or resistant to nalidixic acid.
Table 8. Suggestions for Verification of Antimicrobial Susceptibility Test Results and Confirmationof Organism Identification
This table reflects the drugs listed for testing against the respective organisms in Tables 2A to 2J in M100and gives some examples to consider for verification protocols at a given institution. The list includesphenotypes that: 1) have never been documented; 2) are uncommon; and/or 3) represent results thatcould easily occur from technical errors and which may have significant clinical consequences.
Organism or Group Category Ia
Phenotypes that have not beenreported, are uncommon, and/or
result from technical errors
Category IIb
Phenotypes that may be uncommon at a given institution and/or
result from technical errorsGram-negative organismsEnterobacteriaceae(any)
carbapenem - I or R amikacin - Rfluoroquinolone - R
Citrobacter freundiiEnterobacter spp.Serratia marcescens
ampicillin, cefazolin, or cephalothin- S
Escherichia coli ESBL confirmed positiveKlebsiella spp. ampicillin - S ESBL confirmed positiveProteus vulgarisProvidencia spp.
ampicillin - S
Salmonella spp. 3rd-generation cephalosporin - I or Rd
fluoroquinolone I or R or nalidixic acid - Rd
Pseudomonas aeruginosa
concurrent gentamicin and tobramycin andamikacin - R
Stenotrophomonas maltophilia
carbapenem - S trimethoprim-sulfamethoxazole - R
Haemophilus influenzae
aztreonam - NScarbapenem - NS3rd-generation cephalosporinc - NSfluoroquinolone - NS
ampicillin - R and β-lactamase- negativeamoxicillin-clavulanic acid-R
Neisseria gonorrhoeae
3rd-generation cephalosporin - R fluoroquinolone - R
Any organism Resistant to all agents routinelytested
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For Use With M7-A6–MIC Testing M100-S15Table 8. (Continued)
aCategory I When results listed in this category are observed on individual patient isolates, they should be verified byone or more of the following:
1. Ensuring the unusual results are not due to transcription errors, contamination, or use of adefective panel, plate, or card.
2. Checking previous reports on the patient to determine if the isolate was encountered and verifiedearlier.
3. Confirming the identification of the isolate.4. Repeating the susceptibility test to confirm results. Sometimes it is helpful to use an alternative
test method for the repeat test. 5. For isolates that show results other than susceptible for those antimicrobial agents for which only
susceptible interpretive criteria are provided in Tables 2A to 2J (listed with an “NS” above) and forstaphylococci with vancomycin-intermediate or vancomycin-resistant results: 1) confirm theorganism identification; 2) confirm the antimicrobial susceptibility test results; 3) save the isolate;and 4) submit the isolate to a reference laboratory that will test it by a CLSI/NCCLS referencedilution method.
bCategory II When results listed in this category are observed on individual patient isolates, the verification steps asoutlined for Category I should be considered if the resistance is uncommon in a given institution.
c For these antimicrobial agent/organism combinations, resistance has not been documented to date.
Organism or Group Category Ia
Phenotypes that have not beenreported, are uncommon, and/or
result from technical errors
Category IIb
Phenotypes that may be uncommon at a given institution
and/or result from technical errorsGram-positive organismsEnterococcus spp. daptomycin - NS vancomycin - REnterococcus faecalis ampicillin or penicillin - R
daptomycin - NSlinezolid - Rquinupristin-dalfopristin - S
high-level aminoglycoside - R(particularly if isolate from sterile body site)
Enterococcus faecium daptomycin - NSlinezolid - R
high-level aminoglycoside - R (particularly if isolate from sterilebody site)
quinupristin-dalfopristin - RStaphylococcus aureus daptomycin - NS
linezolid - NSquinupristin-dalfopristin - I or Rvancomycin - I or R
oxacillin - R
Staphylococcus, coagulase-negative
daptomycin - NSlinezolid - NSvancomycin - I or R
Streptococcus pneumoniae
fluoroquinolone - Rlinezolidc - NSvancomycinc - NS
penicillin - R3rd-generation cephalosporin - R
Streptococcus, betagroup
ampicillin or penicillinc - NS3rd-generation cephalosporin - NSdaptomycin - NSlinezolid - NSvancomycinc - NS
Streptococcus, viridansgroup
daptomycin - NSlinezolid - NSvancomycin - NS
penicillin - I or R
Any organism Resistant to all agents routinely tested
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Glossary I (Part 1). ββ-lactams: Class and Subclass Designation and Generic Name
a Penicillinase-labile; hydrolyzed by staphylococcal penicillinase.b Not hydrolyzed by staphylococcal penicillinase.c Cephalosporin I, II, III, and IV are sometimes referred to as 1st-, 2nd-, 3rd, and 4th-generation cephalosporins, respectively.
Cephalosporin III and IV are also referred to as “extended-spectrum cephalosporins.” This does not imply activity against ESBL-producing gram-negativebacteria.
d Although often referred to as a 2nd-generation cephalosporin, cephamycins are not included with the other cephalosporins with regard to reporting of ESBL-producing strains.
e For all confirmed ESBL-producing strains, the test interpretation should be reported as resistant for this antimicrobial class or subclass.
Antimicrobial Class Antimicrobial Subclass Agents Included; Generic Namespenicillins penicillina penicillin
aminopenicillina amoxicillin
ampicillinureidopencillina azlocillin
mezlocillinpiperacillin
carboxypenicillina carbenicillinticarcillin
penicillinase-stablepenicillins
b
cloxacillindicloxacillinmethicillinnafcillinoxacillin
amidinopenicillin mecillinamβ-lactam/β-lactamaseinhibitor combinations
amoxicillin-clavulanic acidampicillin-sulbactampiperacillin-tazobactamticarcillin-clavulanic acid
cephems (parenteral) cephalosporin Ic,e cefazolin
cephalothincephapirincephradine
cephalosporin IIc,e cefamandole
cefonicidcefuroxime (sodium)
cephalosporin IIIc,e cefoperazone
cefotaximeceftazidimeceftizoximeceftriaxone
cephalosporin IVc,e cefepime cephamycind cefmetazole
cefotetancefoxitin
oxacephem moxalactamcephems (oral) cephalosporine cefaclor
cefadroxilcefdinircefditorencefetametcefiximecefpodoximecefprozilceftibutencefuroxime (axetil)cephalexincephradine
carbacephem loracarbefmonobactams aztreonamcarbapenems doripenem
ertapenemimipenemmeropenem
For Use With M7-A6–MIC Testing M100-S15Glossary I (Part 2). Non-ββ-lactams: Class and Subclass Designation and Generic Name
Antimicrobial Class Antimicrobial Subclass Agents Included; Generic Namesaminocyclitols spectinomycin
trospectinomycinaminoglycosides amikacin
gentamicinkanamycinnetilmicinstreptomycintobramycin
ansamycins rifampinquinolones quinolone cinoxacin
garenoxacinnalidixic acid
fluoroquinolone ciprofloxacinclinafloxacinenoxacinfleroxacingatifloxacingemifloxacingrepafloxacinlevofloxacinlomefloxacinmoxifloxacinnorfloxacinofloxacinsparfloxacintrovafloxacin
folate pathway inhibitors sulfonamidestrimethoprimtrimethoprim-sulfamethoxazole
fosfomycins fosfomycinketolides telithromycinlincosamides clindamycinlipopeptides daptomycin
polymyxins colistin polymyxin B
macrolides azithromycinclarithromycindirithromycinerythromycin
nitrofurans nitrofurantoinnitroimidazoles metronidazoleoxazolidinones linezolidglycopeptides glycopeptide oritavancin
vancomycinlipoglycopeptide dalbavancin
teicoplanintelavancin
phenicols chloramphenicolstreptogramins quinupristin-dalfopristintetracyclines doxycycline
minocyclinetetracycline
glycylcycline tigecycline
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Glossary II. Abbreviations/Routes of Administration/Drug Class for Antimicrobial Agents Listedin M100-S15
Antimicrobial Agent Agent Abbreviationa Routes of Administrationb Drug ClassPO IM IV
Amikacin AN, AK, Ak, AMI, AMK
X X aminoglycoside
Amoxicillin AMX, Amx, AMOX, AC
X penicillin
Amoxicillin-clavulanic acid AMC, Amc, A/C, AUG, Aug, XL, AML
X β-lactam/β-lactamase inhibitor
Ampicillin AM, Am, AMP X X X penicillinAmpicillin-sulbactam SAM, A/S,
AMS, ABX β-lactam/β-lactamase
inhibitorAzithromycin AZM, Azi, AZI, AZ X X macrolideAzlocillin AZ, Az, AZL X X penicillinAztreonam ATM, AZT, Azt, AT, AZM X monobactam
Carbenicillin (indanyl salt)
Carbenicillin
CB, Cb, BAR X
X X
penicillin
Cefaclor CEC, CCL, Cfr, FAC, CF X cephemCefadroxil CFR, FAD X cephemCefamandole MA, CM, Cfm, FAM X X cephemCefazolin CZ, CFZ, Cfz, FAZ, KZ X X cephemCefdinir CDR, Cdn, DIN, CD, CFD X cephemCefditoren CDN X cephemCefepime FEP, Cpe, PM, CPM X X cephemCefetamet CAT, FET X cephemCefixime CFM, FIX, Cfe, IX X cephemCefmetazole CMZ, CMZS, CMT X X cephemCefonicid CID, Cfc, FON, CPO X X cephemCefoperazone CFP, Cfp, CPZ, PER, FOP,
CPX X cephem
Cefotaxime CTX, TAX, Cft, FOT, CT X X cephemCefotetan CTT, CTN, Ctn, CTE,
TANS, CNX X cephem
Cefoxitin FOX, CX, Cfx, FX X X cephemCefpodoxime CPD, Cpd, POD, PX X cephemCefprozil CPR, CPZ, FP X cephemCeftazidime CAZ, Caz, TAZ, TZ X X cephemCeftibuten CTB, TIB, CB X cephemCeftizoxime ZOX, CZX, CZ, Cz, CTZ,
TIZX X cephem
Ceftriaxone CRO, CTR, FRX, Cax, AXO, TX
X X cephem
Cefuroxime (axetil)
Cefuroxime (sodium)
CXM, CFX, ROX, Crm, FUR, XM
X
X X
cephem
Cephalexin CN, LEX, CFL X cephemCephalothin CF, Cf, CR, CL, CEP,
CE, KFX cephem
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157©Clinical and Laboratory Standards Institute. All rights reserved.
Glossary II. (Continued) Antimicrobial Agent Agent
Abbreviationa
Routes of Administrationb
Drug Class
PO IM IVCephapirin CP, HAP X X cephemCephradine RAD, CH X cephemChloramphenicol C, CHL, CL X X phenicolCinoxacin CIN, Cn X quinoloneCiprofloxacin CIP, Cp, CI X X fluoroquinoloneClarithromycin CLR, CLM,
CLA, Cla, CHX macrolide
Clinafloxacin CFN, CLX, LF X X fluoroquinoloneClindamycin CC, CM, CD, Cd, CLI,
DAX X X lincosamide
Colistin CL, CS, CT X lipopeptideDalbavancin DAL X glycopeptideDaptomycin DAP X lipopeptideDicloxacillin DX, DIC X penicillinDirithromycin DTM, DT X macrolideDoripenem DOR X carbapenemErtapenem ETP X X carbapenemErythromycin E, ERY, EM X X macrolideFleroxacin FLE, Fle, FLX, FO X X fluoroquinoloneFosfomycin FOS, FF, FO, FM X fosfomycinGarenoxacin GRN X X quinoloneGatifloxacin GAT X X fluoroquinoloneGemifloxacin GEM X fluoroquinoloneGentamicinGentamicin synergy
GM, Gm, CN, GENGM500, HLG, Gms
X X aminoglycoside
Grepafloxacin GRX, Grx, GRE, GP X fluoroquinolone
Imipenem IPM, IMI, Imp, IP X carbapenemKanamycin K, KAN, HLK, KM X X aminoglycosideLevofloxacin LVX, Lvx,
LEV, LEVO, LEX X fluoroquinolone
Linezolid LNZ, LZ, LZD X X oxazolidinoneLomefloxacin LOM, Lmf X fluoroquinoloneLoracarbef LOR, Lor, LO X cephemMecillinam MEC X penicillinMeropenem MEM, Mer, MERO,
MRP, MPX carbapenem
Methicillin DP, MET, ME, SC X X penicillinMezlocillin MZ, Mz, MEZ X X penicillinMinocycline MI, MIN, Min, MN,
MNO, MC, MHX X tetracycline
Moxalactam MOX X X cephemMoxifloxacin MXF X X fluoroquinoloneNafcillin NF, NAF, Naf X X penicillinNalidixic acid NA, NAL X quinoloneNetilmicin NET, Nt, NC X X aminoglycosideNitrofurantoin F/M, FD, Fd, FT,
NIT, NI, FX nitrofurantoin
Norfloxacin NOR, Nxn, NX X fluoroquinoloneOfloxacin OFX, OFL, Ofl, OF X X X fluoroquinoloneOritavancin ORI X glycopeptideOxacillin OX, Ox, OXS, OXA X X X penicillin
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a Abbreviations assigned to one or more diagnostic products in the U.S.b As available in the U.S.
PO per OS (oral)IM intramuscularIV intravenous
©Clinical and Laboratory Standards Institute. All rights reserved.
Glossary II. (Continued)Antimicrobial Agent Agent
Abbreviationa
Routes of Administrationb
Drug Class
PO IM IVPenicillin P, PEN, PV X X X penicillin Piperacillin PIP, PI, PP, Pi X X penicillin Piperacillin-tazobactam TZP, PTZ, P/T, PTc X β-lactam/β-lactamase
inhibitor combinationPolymyxin B PB X lipopeptide
Quinupristin-dalfopristin SYN, Syn, QDA,RP
X streptogramin
Rifampin RA, RIF, Rif, RI,RD
X X ansamycin
Sparfloxacin SPX, Sfx, SPA, SO X fluoroquinolone
Spectinomycin SPT, SPE, SC X X aminocyclitolStreptomycin
Streptomycin synergy
S, STR,StS, SM,
ST2000, HLS
X X aminoglycoside
Sulfonamides SSS, S3 X X folate pathway antagonist(some PO only)
Teicoplanin TEC, TPN, Tei,TEI, TP, TPL
X X glycopeptide
Telavancin TLV X glycopeptideTelithromycin TEL X ketolideTetracycline TE, Te, TET, TC X X tetracyclineTicarcillin TIC, TC, TI, Ti X X penicillinTicarcillin-clavulanic acid TIM, Tim, T/C,
TCC, TLcX β-lactam/β-lactamase
inhibitorTigecycline TGC X glycylcyclineTobramycin NN, TM, TO, To,
TOBX X aminoglycoside
Trimethoprim TMP, T, TR, W X folate pathway inhibitorTrimethoprim-sulfamethoxazole
SXT, SxT, T/S, TS,COT
X X folate pathway inhibitor
Trospectinomycin X X aminocyclitolTrovafloxacin TVA, Tva, TRV, TV X X fluoroquinolone
Vancomycin VA, Va, VAN X X glycopeptide
©Clinical and Laboratory Standards Institute. All rights reserved. 159
For Use With M7-A6–MIC Testing M100-S15
Agent Abbreviation Antimicrobial Agents for Which RespectiveAbbreviation is Used
AZM Azithromycin, AztreonamAZ Azithromycin, Azlocillin
CB, Cb Ceftibuten, CarbenicillinCFR, Cfr Cefaclor, Cefadroxil
CF, Cf Cefaclor, CephalothinCM Clindamycin, Cefamandole
CFM, Cfm Cefixime, CefamandoleCZ, Cz Ceftizoxime, CefazolinCD, Cd Clindamycin, Cefdinir
CPZ Cefprozil, CefoperazoneCP, Cp Cephapirin, Cefoperazone, CiprofloxacinCN, Cn Cephalexin, Cefotetan, Cinoxacin, Gentamicin
CFX, Cfx Cefoxitin, CefuroximeCL Cephalothin, ChloramphenicolCH Clarithromycin, CephradineDX Doxycycline, DicloxacillinFO Fleroxacin, FosfomycinSC Spectinomycin, MethicillinSO Sparfloxacin, OxacillinTC Tetracycline, Ticarcillin
List of Identical Abbreviations Used for More Than One Antimicrobial Agent inU.S. Diagnostic Products
Iden
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Summary of Comments and Subcommittee Responses
M100-S14: Performance Standards for Antimicrobial Susceptibility Testing; Fourteenth InformationalSupplement (M7—MIC Testing)
General
1. It has come to my attention that there are conflicting guidelines regarding interpretation of MICs which couldresult in confusion and subsequent mistreatment, harm, and even death of patients. For example, currentCLSI/NCCLS guidelines for vancomycin susceptibility state that the organism is resistant with an MIC >1.0 ifit is a streptococcus but sensitive up to an MIC of 4.0 if it is a staphylococcus. Clearly, any organism, staph orstrep, with an MIC <5 would be inhibited by vancomycin in a patient with therapeutic levels. Current guidelinescould result in inappropriate isolation and treatment of many patients with certain strep infections. Clearly,MIC interpretations should be based more on expected tissue and serum drug concentrations.
• CLSI/NCCLS interpretive criteria are established using a combination of microbiologic (e.g., populationdistribution data), pharmacokinetic/pharmacodynamic, and clinical response data. A drug can havedifferent levels of activity against one genus versus another for several reasons, among which are thelocation of the target site in the cell, the accessibility of the drug to the target site, and whether the drugexhibits cidal or static activity. Because of this, there are no universal breakpoints that are appropriatefor all organisms. In addition, when there is no known resistance to a particular drug, the susceptiblebreakpoint is usually set just above the upper MIC range of the normal or wild type population so thatemerging resistant populations can be detected. For example, the MICs of vancomycin for the wild typepopulation of streptococci are less than 1 µg/mL, whereas the wild type population of staphylococciincludes strains with vancomycin MICs of 2 or 4 µg/ml. Therefore, the susceptible vancomycinbreakpoint has been set at 1 µg/mL for streptococci and 4 µg/ml for staphylococci. If strains ofstreptococci were to develop vancomycin MICs >1 µg/mL, then it would be appropriate to thenreevaluate clinical and microbiological data and possibly adjust the interpretive criteria.
2. Amoxicillin-sulbactam is marketed and prescribed in more than 20 countries all over the world. The breakpointscannot be extrapolated from the results of amoxicillin-clavulanate or ampicillin-sulbactam, even though crosssusceptibility among these drugs does exist. We feel that this point should be clarified in CLSI/NCCLSrecommendations.
• Clinical and Laboratory Standards Institute is able to establish interpretive criteria only forantimicrobial agents which have been presented and discussed at CLSI meetings. If sufficient dataconforming to CLSI/NCCLS document M23—Development of In Vitro Susceptibility Testing Criteria andQuality Control Parameters for amoxicillin-sulbactam were presented to the subcommittee, we wouldconsider a request for interpretive criteria for that compound.
3. Sodium fosfomycin (not trometamol) is commonly used in Latin America for the treatment of severalinfections. Seven Latin American countries use cefoperazone-sulbactam for severe infections. No breakpointsare available for either compound.
• There are breakpoints in the current documents for Enterococcus faecalis and Escherichia coli for oralfosfomycin. If sufficient data conforming to CLSI/NCCLS document M23—Development of In VitroSusceptibility Testing Criteria and Quality Control Parameters for sodium fosfomycin and forcefoperazone-sulbactam were presented to the subcommittee, we would consider a request forinterpretive criteria for those compounds.
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Table 2A
4. In South America, azithromycin (AZ) is at present largely used for the treatment of bacterial gastroenteritis dueto Salmonella spp. or Shigella spp. Breakpoints for the assay of AZ against these isolates should be included.
• If data conforming to CLSI/NCCLS document M23—Development of In Vitro Susceptibility TestingCriteria and Quality Control Parameters are presented to the subcommittee, we would consider addinginterpretive criteria for azithromycin for these organisms.
5. In South America, ESBLs are frequently found in Proteus mirabilis, Salmonella (non-typhi) and Shigella spp.Why does Clinical and Laboratory Standards Institute consider only E. coli and Klebsiella spp. for ESBLdetection? Use of cefotaxime, ceftazidime and cefepime should be encouraged for the phenotypic detection ofESBLs.
• We have recently carried out a study to determine the suitability of the ESBL screening and confirmationtests for P. mirabilis and that organism has been added to the ESBL table in Table 2A in M2 and M7 alongwith E. coli, K. pneumoniae, and K. oxytoca. Although the use of cefepime for characterizing ESBLs hasbeen described, criteria for the use of cefepime with and without clavulanate has not been studiedsufficiently to date to be included in the document. The same is true for Salmonella and Shigella spp.,which precludes adding them to the list at this time.
Table 2C
6. We currently do not perform any definitive identification testing on any coagulase-negative staphylococci(CoNS). We do a rapid latex, and if negative, report as CoNS. In M100-S14, the text states that testing for mecAor PBP 2a is to be performed on non-S. epidermidis isolates. Are you then saying that I must now performdefinitive identification for all coagulase-negative staphylococci?
• The Clinical and Laboratory Standards Institute does not require identification of coagulase-negativestaphylococci to the species level, with two exceptions: 1) laboratories should identify S. saprophyticus inurinary isolates for which susceptibility testing is not recommended; and 2) laboratories should identifyS. lugdunensis, an uncommon pathogen, but one that can cause endocarditis. For laboratories that do notwish to identify all coagulase-negative staphylococci to species level, S. saprophyticus and S. lugdunensiscan be easily identified using a few simple tests (Clinical Microbiology Procedures Handbook, 2nd edition,2004, ASM Press; Manual of Clinical Microbiology, 8th edition 2003, ASM Press). S. saprophyticus isnovobiocin resistant at ≤≤ 16 mm on Mueller-Hinton agar. S. lugdunensis can be identified usingpyrrolidonyl arylamidase and ornithine decarboxylase. S. lugdunensis is strongly PYR positive andornithine decarboxylase positive. A simple scheme for identification of S. lugdunensis has also beenproposed by Schnitzler, et al. (J Clin Microbiol, 36:812-13;1998).
7. If we have a patient with pure culture of coagulase-negative staphylococci from a lower respiratory specimen,a wound, or a catheter tip, are you suggesting that because these are not sterile sites, we should not beperforming the mecA testing? Is this mecA test ONLY for sterile site specimens, or is it for serious infectionsand sites? You know that a terminology of “serious infection” falls into a gray zone.
• The definition of serious infection should be institution-specific. Laboratories, in consultation withinfectious disease clinicians, should decide which specimens warrant additional testing of CoNS for mecAor PBP 2a. For example, isolates from endocarditis and osteomyelitis would fall into this category.
8. I have a question regarding the use of the cefoxitin disk to predict for oxacillin resistance in Staphylococcusspecies as outlined in M100-S14. The following two statements in the document are in themselves easilyunderstood.
M100-S14, page 104, Warning 2, states, “For oxacillin-resistant Staphylococcus aureus and coagulase-negativestaphylococci, all penicillins, cephems, and other ß-lactams...may appear active in vitro but are not effectiveclinically. Results for these drugs should be reported as resistant or should not be reported.” C
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M100-S14, page 105, comment 10, states, “For oxacillin-susceptible strains, results for parenteral and oralcephems, ß-lactam/ß-lactamase inhibitor combinations, and carbapenems, if tested, should be reportedaccording to the results generated using routine interpretative criteria.”
It is when I attempt to combine the information that I am becoming confused.
Let’s say that I have a Staphylococcus species with MICs for oxacillin and cefazolin which interpret as resistant,but the cefoxitin disk diffusion interpretation is susceptible. Do I change the cephems, and other ß-lactams tosusceptible as well, following the logic of page 104, warning 2, or do I leave the cephems and other ß-lactamsas resistant in accordance with comment 10 on page 105?
• Testing of staphylococci against cefazolin and cefoxitin using an MIC method is not recommended.Determination of oxacillin susceptibility is best done with oxacillin when using an MIC method and bycefoxitin when doing disk diffusion. These phenotypic test methods correlate best with the presence orabsence of the mecA gene, which is associated with oxacillin resistance. Susceptibility to cefazolin andother cephems should be predicted using oxacillin when performing an MIC test or cefoxitin (foroxacillin) when performing disk diffusion.
9. If I were to not perform any definitive identification on coagulase-negative staphylococci isolates andperformed the mecA test, what are the implications if the isolate was truly an S. epidermidis?
• Tests for mecA and the gene product PBP 2a are accurate and rapid methods for detecting oxacillinresistance in S. aureus and coagulase-negative staphylococci including S. epidermidis.
10. In Table 2C (M7), comment 10, is this mecA testing for coagulase-negative staphylococci isolates only, or is italso for S. aureus?
• See the response to comment 9.
11. I have a question regarding the testing of coagulase-negative staphylococci isolates with cefoxitin. We use anautomated system and this particular drug is not on the conventional panel that we test. Dropping a disk wouldinvolve keeping Mueller-Hinton agar on hand and performing QC on the disks. Is this testing for sterile sitesonly? Is this a rule or just a recommendation? We would appreciate any guidance on this matter.
• Determination of oxacillin susceptibility is best done with oxacillin when using an MIC method and bycefoxitin when performing disk diffusion. These phenotypic test methods correlate best with the presenceor absence of the mecA gene, which mediates oxacillin resistance. When using an automated system, avalidation study should be performed prior to routine use to determine if it accurately predicts oxacillinsusceptibility.
12. Why is Clinical and Laboratory Standards Institute moving to the cefoxitin disk screen test for oxacillinresistance detection in staphylococci? It is clear that there is better correlation between oxacillin resistance andmecA detection or the latex test for PBP 2a. This information should be stated in the CLSI recommendations.
• For S. aureus and S. lugdunensis, the cefoxitin disk test is comparable to the oxacillin disk test forprediction of mecA-mediated resistance to oxacillin; however, the cefoxitin disk test is easier to read andtherefore it is the preferred method. For coagulase-negative staphylococci, oxacillin interpretive criteriacorrelate with the presence or absence of the gene encoding oxacillin resistance (mecA) in S. epidermidis;however, these interpretive criteria may overcall resistance for other coagulase-negative staphylococci(e.g., S. saprophyticus). For coagulase-negative staphylococci, the cefoxitin disk test has greater specificitythan oxacillin and equal sensitivity, although it may miss some strains of mecA-positive S. simulans. It istrue, however, that mecA detection and the latex test for PBP 2a are the most accurate predictors ofmecA-mediated resistance and these tests should be used when available and clinically relevant. However,not all laboratories have the resources to perform these tests. Please also see the response to comment 11.
Com
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t Sum
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IC
©Clinical and Laboratory Standards Institute. All rights reserved. 163
Vol. 25 No. 1 M100-S15
Related CLSI/NCCLS Publications*
M2-A8 Performance Standards for Antimicrobial Disk Susceptibility Tests; Approved Standard—Eighth Edition (2003).This standard contains updated recommended techniques, interpretive criteria, and quality control parameters for disk susceptibility testing.
M7-A6 Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria That Grow Aerobically; ApprovedStandard—Sixth Edition (2003). This standard provides updated reference methods for the determination of minimalinhibitory concentrations (MICs) for aerobic bacteria by broth macrodilution, broth microdilution, and agar dilution.
M11-A6 Methods for Antimicrobial Susceptibility Testing of Anaerobic Bacteria; Approved Standard—Sixth Edition(2004). This standard provides reference methods for the determination of minimal inhibitory concentrations (MICs)of anaerobic bacteria by broth microdilution and agar dilution.
M23-A2 Development of In Vitro Susceptibility Testing Criteria and Quality Control Parameters; Approved Guideline—Second Edition (2001). This document addresses the required and recommended data needed for the selection ofappropriate interpretive standards and quality control guidelines for antimicrobial agents.
M31-A2 Performance Standards for Antimicrobial Disk and Dilution Susceptibility Tests for Bacteria Isolated fromAnimals; Approved Standard—Second Edition (2002). This document provides the currently recommendedtechniques for antimicrobial agent disk and dilution susceptibility testing, criteria for quality control testing, andinterpretive criteria for veterinary use.
M37-A2 Development of In Vitro Susceptibility Testing Criteria and Quality Control Parameters for VeterinaryAntimicrobial Agents; Approved Guideline—Second Edition (2002). This document addresses the required andrecommended data needed for selection of appropriate interpretative standards and quality control guidance for newveterinary antimicrobial agents.
M39-A Analysis and Presentation of Cumulative Antimicrobial Susceptibility Test Data; Approved Guideline (2002).This document describes methods for the recording and analysis of antimicrobial susceptibility test data, consisting ofcumulative and ongoing summaries of susceptibility patterns of epidemiologically significant microorganisms.
_____________* Proposed- and tentative-level documents are being advanced through the Clinical and Laboratory Standards Institute consensusprocess; therefore, readers should refer to the most recent editions.
January 2005 M100-S15
©Clinical and Laboratory Standards Institute. All rights reserved.164
NOTES
Vol. 25 No. 1 M100-S15
©Clinical and Laboratory Standards Institute. All rights reserved. 165
NOTES
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©Clinical and Laboratory Standards Institute. All rights reserved.166
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©Clinical and Laboratory Standards Institute. All rights reserved. 167
NOTES
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