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Antimicrobial Stewardship David Meyer, PharmD Clinical Pharmacy Manager Fairmont General Hospital. Objectives. Identify types of antimicrobial resistance Discuss multi-drug resistant organisms and possible treatment options Describe the basic framework of an antimicrobial stewardship program. - PowerPoint PPT Presentation
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Antimicrobial Stewardship
David Meyer, PharmDClinical Pharmacy ManagerFairmont General Hospital
Objectives
Identify types of antimicrobial resistance
Discuss multi-drug resistant organisms and possible treatment options
Describe the basic framework of an antimicrobial stewardship program
Antimicrobial Resistance
Clin Infect Dis. (2011) 52 (suppl 5): S397-S428.
Antimicrobial Resistance:Selective Pressure
Mulvey M R , Simor A E CMAJ 2009;180:408-415
Antimicrobial Resistance:Mechanisms of genetic resistance to antimicrobial agents
Coates A et al. Nature Reviews Drug Discovery 1, 895-910 (November 2002)
Antimicrobial Resistance:Mutation & Selection/Acquired Resistance
Enzyme Inactivation -lactamase production ESBL production Carbapenemase New Delhi Metallo- -lactamase
Examples: E. coli producing -lactamase or ESBL Klebsiella producing carbapenemase
Antimicrobial Resistance:Mutation & Selection/Acquired Resistance
Alteration of the target site Altered protein binding Altered DNA enzymes
Examples: MRSA – methicillin-resistant Staph. aureus PBP (Penicillin binding protein)-resistant Strep. pneumo Ciprofloxacin resistance in Mycobacterium
Antimicrobial Resistance:Mutation & Selection/Acquired Resistance
Decreased access to the target site Efflux pumps - Antimicrobial is pumped out of the
bacteria before it accumulates Altered structure of outer membrane proteins or porins
Example: Tetracycline TetK efflux in Staph. aureus Imipenem-resistant Pseudomonas
Examples of Common Resistant Bugs
CMAJ February 17, 2009 vol. 180 no. 4 408-415
Multi-Drug Resistant Organisms (MDROs)
Prevalent in hospitals & long-term care facilities Not as likely to cause disease in LTCF (colonization)
Cause the same infections as non-MDROs BUT Fewer antibiotic choices Isolation Increased length of stay Increased risk of ADE Increased mortality
= Increased $$$
MDRO Treatment Options: Community-acquired MRSA (Ca-MRSA)
Transmission Contaminated hands Skin-to-skin contact Crowded conditions Poor hygiene
Increased risk Athletes, military recruits, children, Pacific Islanders,
indigenous populations, men who have sex with men, animal owners, ED patients, cystic fibrosis patients, urban underserved communities, and prisoners
Clinical Microbiology Reviews, July 2010, p. 616-687, Vol. 23, No. 3
Clin Infect Dis. (2011) 52 (suppl 5): S397-S428. doi: 10.1093/cid/cir153
Mild-moderate infection Doxycycline or Minocycline
Caution with susceptibility tests Clindamycin Trimethoprim/Sulfamethoxazole
Severe infection Vancomycin - PREFERRED Daptomycin (NOT for pneumonia) Linezolid (pneumonia) Dalfopristin/Quinupristin
Limited by ADE arthralgias Tigecycline (cSSTI, intra-ab)
Low serum concentrations Telavancin (cSSTI) Ceftaroline (cSSTI)
**Use varies greatly by site of infection, refer to IDSA MRSA Guidelines 2011**
*Adjuncts: rifampin (also in combo with FQs), gentamicin, beta-lactams
Clinical Microbiology Reviews, July 2010, p. 616-687, Vol. 23, No. 3
Clin Infect Dis. (2011) 52 (suppl 5): S397-S428. doi: 10.1093/cid/cir153Gilbert DN, et al. Sanford Guide to Antimicrobial Therapy 2011, 41st ed.
MDRO Treatment Options: Community-acquired MRSA (Ca-MRSA)
MDRO Treatment Options:Penicillin-Resistant Strep. Pneumoniae (PRSP)
Causes respiratory tract infections and meningitis
Resistant to: Penicillin G
*due to alteration in penicillin-binding proteins (PBPs)
Variable resistance to cephalosporins, macrolides, tetracyclines, clindamycin
Alternatives: Amoxicillin/clavulanate Ceftriaxone, cefotaxime Respiratory quinolones Linezolid Vancomycin +/- Rifampin
Am J Respir Crit Care Med ; 2005 ; 171 : 388 -416 Gilbert DN, et al. Sanford Guide to Antimicrobial Therapy 2011, 41st ed.
MDRO Treatment Options: Vancomycin-resistant Enterococci (VRE)
Usually Enterococcus faecium Resistant to:
Vancomycin, Aminoglycosides, Penicillins, Quinolones Treatment options:
Linezolid Quinupristin/dalfopristin
Faecium only Combination therapy recommended
Tigecycline Daptomycin Site Specific– Urinary Tract Infections
Nitrofurantoin Fosfomycin
CMI 16:555,2010 Gilbert DN, et al. Sanford Guide to Antimicrobial Therapy 2011, 41st ed.
Clin Infect Dis. (2010) 51 (1): 79-84 http://emedicine.medscape.com/article/216993-treatment
MDRO Treatment Options:Pseudomonas aeruginosa
Resistant to: Meropenem, Imipenem
Alternatives: Possible evidence for extended-infusion carbapenems Fluoroquinolones – cipro > levo Anti-pseudomonal aminoglycosides (APAG) Anti-pseudomonal penicillins +/- APAG Ceftazidime, Cefepime +/- APAG Aztreonam Combos of Doripenem + Polymyxin B +/- Rifampin Fosfomycin + APAG Polymyxin B Colistin
Lister PD, Wolter DJ Clin Infect Dis 2005;40:S105-114 Livermore DM. Clin Infect Dis 2002;34:634-40Am J Respir Crit Care Med ; 2005 ; 171 : 388 -416 Gilbert DN, et al. Sanford Guide to Antimicrobial Therapy 2011, 41st ed.Antimicrob Agents Chemother. 2008 October; 52(10): 3795–3800
MDRO Treatment Options:Extended Spectrum Beta Lactamase (ESBL)-Producing Organisms
Risk Factors for ESBLs in non-hospitalized patients Recent antibiotic use Residence in long-term care facility Recent hospitalization Age >65 years Male
34% of ESBL-producing isolates from patients with no recent health care contact
Ben-Ami R et al. Clin Infect Dis 2009;49:682-90
MDRO Treatment Options: ESBL-producing Organisms
Most commonly Klebsiella or E.coli
Resistant to: 2nd/3rd generation Cephalosporins Aztreonam Aminoglycosides Fluoroquinolones
Alternatives: Carbapenems (some emerging resistance)
Ertapenem for E. coli In-vitro: Cefepime, Piperacillin/tazobactam, Tigecycline Colistin Fosfomycin
Am J Respir Crit Care Med ; 2005 ; 171 : 388 -416 Gilbert DN, et al. Sanford Guide to Antimicrobial Therapy 2011, 41st ed.
MDRO Treatment Options:Carbapenemase and New Delhi Metallo
KPC = CRE Most commonly Klebsiella or E.coli NDM-1 found in water samples in India Resistant to:
All Carbapenems Aminoglycosides Fluoroquinolones
Alternatives: Tigecycline Colistin
MDRO Treatment Options: Acinetobacter
Up and coming “superbug”
Found in soil and water
Can live on skin & surfaces for days
Predominately a colonizing organism
Therapy: ID Consult!
Agents: Carbapenems (building resistance as of 2005)
Susceptibility 32% to >90% Ampicillin/sulbactam +/- Meropenem Tigecycline - in combination only (e.g. + Amikacin) Polymyxin B + Imipenem/cilastatin + Rifampin Colistin
Susceptibility 55% to >80%
Other treatment therapies and combinations but Acinetobacter infections very MDRO: Mortality 20-50%
MDRO Treatment Options: Acinetobacter
Landman D et al. Arch Intern Med 2002;162:1515-20 Kopterides P et al. Int J Antimicrob Agents 2007;30:409-14
Clin Infect Dis. (2010) 51 (1): 79-84 Am J Respir Crit Care Med ; 2005 ; 171 : 388 -416Gilbert DN, et al. Sanford Guide to Antimicrobial Therapy 2011, 41st ed.
Antimicrobial Stewardship
http://www.hhnmag.com/hhnmag/gateFold/PDF/05_2012/HHN_May2012Cover.pdf
IDSA Definition
Antimicrobial Stewardship is an activitythat promotes:
– The appropriate selection of antimicrobials.– The appropriate dosing of antimicrobials.– The appropriate route and duration of antimicrobial therapy.
What is an Antimicrobial Stewardship Program (ASP)
Dellit TH, Owens RC, McGowan JE Jr et al. Infectious Diseases Society of America and the Society for Healthcare Epidemiology of America guidelines for 1. developing an institutional program to enhance antimicrobial stewardship. Clin Infect Dis. 2007; 44:159-77
Antimicrobial Stewardship – Why?
Boucher et al. Clin Inf Dis 2009
Not much in the pipeline
World Health Organization (WHO) 10 x ’20 Initiative
Published in early 2010 by IDSA
WHO identified antimicrobial resistance as a major issue
Clin Infect Dis. (2011) 52 (suppl 5): S397-S428. doi: 10.1093/cid/cir153
Clin Infect Dis 2010;50:1081-83.
Antimicrobial Stewardship Programs (ASP)
Plethora of literature on resistance and ASP Refer to local Antibiograms for most accurate resistant patterns
leadstewardship.org and ASHP Educational Webinars under Infectious Diseases subsection
Existing Webinars Summarize IDSA Guidelines (2007)
http://cid.oxfordjournals.org/content/44/2/159.full ASP-supportive literature Success stories
Personal & in literature
Our focus: Key points, focused approach, resources
Purpose
Optimize clinical outcomes
Minimize unintended consequences of antimicrobial use Toxicity Selection of pathogenic organisms (e.g. C. diff) Emergence of resistance
2007 IDSA ASP Guidelines: Dellit TH. Clin Infect Dis 2007;44:159-77.
ASP Guidelines Core Strategies Core Strategies
Prospective audit with intervention and feedback Looking at antibiotic orders as they come, adjusting per pre-set guidelines
Formulary restriction with pre-authorization UKMC: negative impact (let first dose go thru, intervene after)
Supplemental Strategies Education, Education, Education Guidelines and clinical pathways Antimicrobial order forms (CPOE systems) Combination therapy De-escalation Dose optimization IV to PO conversion Antimicrobial cycling (least evidence, most controversial)
2007 IDSA ASP Guidelines: Dellit TH. Clin Infect Dis 2007;44:159-77.ASHP Midyear 2010 CE Presentation – Antimicrobial Stewardship: Building the Case and Overcoming Barriers in your Institutionhttp://www.ashpmedia.org/symposia/4cpe/stewardship/
CDC: Methods to Improve Antimicrobial Use
Passive prescriber education Standardized order forms Formulary restrictions Pre-authorization Pharmacy substitution Multidisciplinary DUE Performance feedback CPOE
CDC: http://www.cdc.gov/ncidod/dhqp/pdf/ar/mdroGuideline2006.pdf
Guiding Tenets of ABX Use
1. Severe infection – start broad Get it wrong = in trouble
2. Get it IN the patient quickly (actual administration) First dose = most important
3. De-escalation of therapy is a necessity Right drug = narrowest-spectrum with successful
response, causing the least collateral damage
4. Treat only as long as appropriate
ASHP Midyear 2010 – Antimicrobial Stewardship: Building the Case and Overcoming Barriers in your Institution: http://www.ashpmedia.org/symposia/4cpe/stewardship/
ASP Team Members Multidisciplinary problem that cannot be solved by
one person
Core members (eventual compensation is ideal) ID MD ID Pharmacist
Adjunct members Microbiologist IT/Data Specialist Infection Control Professional and/or Epidemiologist
2007 IDSA ASP Guidelines: Dellit TH. Clin Infect Dis 2007;44:159-77.
Roles of the Team Members
Physician Champion Knowledgeable in Infectious Diseases Willing to teach untrained Pharmacist Willing to help promote cause Willing to work together Respected by peers Able to form working relationship with hospital administrator and
pharmacy director
*sometimes the largest hurdle to overcome
2007 IDSA ASP Guidelines: Dellit TH. Clin Infect Dis 2007;44:159-77.
Roles of the Team Members
Clinical Pharmacist ID-trained or strong willingness to learn backed by
a solid foundation in antibiotics Helps establish program structure and protocol Aids in creating and/or overseeing Antibiograms Performs daily interventions Continually educates medical and pharmacy staff Raises pharmacy awareness and rallies support
2007 IDSA ASP Guidelines: Dellit TH. Clin Infect Dis 2007;44:159-77.
Roles of the Team Members
Microbiologist Provides surveillance data for Antibiogram Develops combination antibiotic Antibiograms Reviews current diagnostic tests and investigates
pros and cons of incorporating new, novel tests
2007 IDSA ASP Guidelines: Dellit TH. Clin Infect Dis 2007;44:159-77.
Roles of the Team Members
Infection Control and/or Epidemiologist Implement/improve infection control measures Collect data regarding adherence and outcomes Monitor healthcare-acquired infection rates Investigate local outbreaks Share daily reports with pharmacist
Isolation due to MDROs
2007 IDSA ASP Guidelines: Dellit TH. Clin Infect Dis 2007;44:159-77.
Roles of the Team Members
IT/Data Manager Establish method for obtaining data Develop/adapt database to record interventions Prepare annual reports for administrative arm Aid in statistical analysis of program
*most programs lack this member and the pharmacist picks up the slack
2007 IDSA ASP Guidelines: Dellit TH. Clin Infect Dis 2007;44:159-77.
Performance Measures
Essential in showing value of Stewardship program
Examples: Antibiogram
Performed at least annually
Medication Use Evaluations (MUE) Utilization/Purchasing Data quarterly MDRO rates Blood contamination Rates Quality Measures
Can this be done at smaller hospitals?
120 bed hospital in Monroe, LA ID MD, clinical PharmD, infection control, microbiologist
*paid MD and PharmD
Concurrent chart review 3 days/week (limited resources) Study period = 1 year (all the way back in 2000)
Targeted patients Multiple, prolonged, or high-cost antibiotics
Initial pushback from medical staff 69% recommendation acceptance 19% reduction in antibiotic expenditures (saved $177,000!)
LaRocco et al. CID 2003.
Tier System Approach
Different approaches for different budgets/personnel
Low-lying fruit Start small, simple, and smart Identify “Problem Child” units or antibiotics Easy “wins” Build ASP credibility IV to PO Conversions; De-escalation of therapy; Pre-printed
order sets
Raising awareness costs = $0 Improve the systems you already have in place
CDC’s 4 Principles:
1. Infection prevention•Catheters , VAP
2. Accurate and prompt diagnosis and treatment•Etiology of infectious process
3. Prudent use of antimicrobials
4. Prevention of transmission •Hand washing, isolation, etc.
CDC: http://www.cdc.gov/ncidod/dhqp/pdf/ar/mdroGuideline2006.pdf
A Few Examples:Management of MDRO in Healthcare Settings
A Few Examples:Restriction vs. Facilitation
Consider Facilitation vs. Restriction
The goal of an ASP is NOT to limit appropriate use of antibiotics
More restricted antibiotics = sicker patient usually is More delay More pushback from medical staff Mixed signal of ASP
The only dose proven to save lives in the first one! Allow according to restriction protocol, then adjust prn
ASHP Midyear 2010 – Antimicrobial Stewardship: Building the Case and Overcoming Barriers in your Institution:http://www.ashpmedia.org/symposia/4cpe/stewardship/
Many Available Resources
ASHP – ashp.org IDSA – idsociety.org CDC – cdc.gov CID – cid.oxfordjournals.org
Available for purchase Sanford Guide to Antimicrobial Therapy Johns Hopkins ABX Guide
hopkins-abxguide.org
ASP: Why now?
1. Antimicrobial overuse/misuse affects resistance
2. Antimicrobial resistance is at unprecedented levels
3. Typically financially self-supporting Although this should be a secondary goal
4. It’s the RIGHT THING TO DO
ASHP Midyear 2010 – Antimicrobial Stewardship: Building the Case and Overcoming Barriers in your Institution: http://www.ashpmedia.org/symposia/4cpe/stewardship/
What is the status of ASP in your institution?
Question posed by speaker at ASHP Midyear Meeting 2010
10% No ASP, no plans to pursue one 20% No ASP, need to establish one 30% Currently discussing need for an ASP 20% The ASP we have is not very effective 20% The ASP we have is highly regarded
So if you don’t have an ASP, you’re not alone but you may be soon
ASHP Midyear 2010 – Antimicrobial Stewardship: Building the Case and Overcoming Barriers in your Institution:
http://www.ashpmedia.org/symposia/4cpe/stewardship/
Barriers to Establishing ASPs1. Lack of funding
ASPs often function in personnel’s spare time initially
2. Shortage of adequately-trained ID MDs and Pharmacists
3. Lack of pharmacy leadership support
4. MD autonomy
5. Competition for funding Money is going to go to programs that are mandated
6. Antagonistic colleagues
ASHP Midyear 2010 – Antimicrobial Stewardship: Building the Case and Overcoming Barriers in your Institution: http://www.ashpmedia.org/symposia/4cpe/stewardship/
Owens RC, Shorr AF, Deschambeault AL. Antimicrobial stewardship: shepherding precious resources. Am J Health-Syst Pharm. 2009; 66(Supp 4):S15-22
Building your Case
1. Current situation is likely costing institution unnecessary dollars
2. Clinical issues make timely program implementation compelling
3. A formal business plan is essential
4. Need to demonstrate return on investment (ROI) over a reasonable time period
ASHP Midyear 2010 – Antimicrobial Stewardship: Building the Case and Overcoming Barriers in your Institution:http://www.ashpmedia.org/symposia/4cpe/stewardship/
Conclusion:Baby Steps
Avoid making cost-reduction your #1 goal
Educate personnel on ASP Basics
Identify glaring problem areas and establish areas of improvement
Work on multidisciplinary development of evidence-based guidelines Based on national guidelines, tailored to institution based on resistance patterns
Work to ensure de-escalation and antibiotic stop dates
Improve efficiency of pharmacy distribution system Facilitation vs. Restriction
ASHP Midyear 2010 – Antimicrobial Stewardship: Building the Case and Overcoming Barriers in your Institution:
http://www.ashpmedia.org/symposia/4cpe/stewardship/
Conclusion:Needs identified by IDSA in 2011 publication
National Funding
Legislative action
Research and Development ASPs Novel Antibiotics Resistance, especially as it relates to MDROs
Clin Infect Dis. (2011) 52 (suppl 5): S397-S428. doi: 10.1093/cid/cir153
ASP Resources
Online Webinars http://www.ashp.org/menu/Education/OnlinePrograms.aspx http://leadstewardship.org/activities.php
ASP-specific Websites Nebraska Medical Center
www.nebraskamed.com/asp Univ. of Kentucky
www.hosp.uky.edu/pharmacy/AMT/default.html Univ. of Pennsylvania
www.uphs.upenn.edu/bugdrug
Goff, DA. ASHP Advantage Newsletter. CE in the Mornings. Working Together: Implementing Interdisciplinary Antimicrobial Stewardship Programs. March 2010.
Questions?