Antimicrobial Stewardship Jeffrey S. Gerber, MD, PhD Assistant Professor of Pediatrics University of...
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Antimicrobial Stewardship Jeffrey S. Gerber, MD, PhD Assistant Professor of Pediatrics University of Pennsylvania School of Medicine Division of Infectious
Antimicrobial Stewardship Jeffrey S. Gerber, MD, PhD Assistant
Professor of Pediatrics University of Pennsylvania School of
Medicine Division of Infectious Diseases The Childrens Hospital of
Philadelphia
Slide 2
Topics The case for Antimicrobial Stewardship Define and
Discuss Data for ASPs Examples of Stewardship
Slide 3
Magnitude of Antibiotic Use antibiotics are the second most
commonly used class of drugs in the US ($8 billion/yr) 60% of
children admitted to freestanding childrens hospitals receive
antibiotics 50% of antibiotic use is inappropriate
Slide 4
Anti-infective use in US Hospitals Hoffman et al. Am J Health
Syst Pharm. 2012 Mar 1;69(5):405-21
Slide 5
Total outpatient antibacterial use in the United States and 27
European countries in 2004 (total use for Greece, Iceland, and
Bulgaria, 2002 data for Poland, and 2003 data for Italy). Goossens
H et al. Clin Infect Dis. 2007;44:1091-1095 2007 Infectious
Diseases Society of America
Slide 6
Top 1 through 6 drug markets according to the total estimated
number of outpatient prescriptions dispensed to the US pediatric
population (ages 017 years) from US retail pharmacies, 2002 through
2010. *Statistically significant linear trend at P value =.05. Chai
G et al. Pediatrics 2012;130:23-31 2012 by American Academy of
Pediatrics
Slide 7
Adverse effects of Antibiotic use antibiotics are the most
common cause of ED visits for adverse drug events in children use
drives resistance antibiotic-resistant infections: $20 billion in
excess healthcare costs $35 billion in societal costs 8 million
additional hospital days
Slide 8
Antibiotic Resistance
Slide 9
CDC described antibiotic resistance as "one of the world's most
pressing health problems the WHO has identified antibiotic
resistance as "one of the three greatest threats to human
health."
Slide 10
Slide 11
5%25% diarrhea 1 in 1000 visit emergency department for adverse
effect of antibiotic comparable to insulin, warfarin, and digoxin 1
in 4000 chance that an antibiotic will prevent serious complication
from URI Shehab N. CID 2008:47; Linder JA. CID 2008:47 Resistance
Aside
Slide 12
Slide 13
A, Proportion of subjects developing IBD according to age and
antianaerobic antibiotic exposure status. Kronman M P et al.
Pediatrics 2012;130:e794-e803 2012 by American Academy of
Pediatrics
Slide 14
Antibiotics in early life alter the murine colonic microbiome
and adiposity Mice fed subtherapeutic doses of antibiotics
exhibited: Increased adiposity Increased hormone levels related to
metabolism Taxonomic changes of microbiome Changes in copies of key
genes involved in metabolism of carbohydrates to short-chain fatty
acids Alterations in hepatic metabolism of lipids and cholesterol
Increase in colonic levels of short chain fatty acids Cho I et al.
Nature 2012
Slide 15
Slide 16
Topics The case for Antimicrobial Stewardship Define and
Discuss Data for ASPs Examples of Stewardship
Slide 17
optimal selection, dosage, and duration of antimicrobial
treatment that results in the best clinical outcome for the
treatment or prevention of infection with minimal toxicity to the
patient and minimal impact on subsequent resistance Owens RC,
Pharmacotherapy 2004 Antimicrobial Stewardship: Definition
Slide 18
ASP a quality improvement initiative proven in multiple,
peer-reviewed studies to: improve patient outcomes shorten length
of stay reduce Clostridium difficile infection rates reduce
antimicrobial resistance save money Antimicrobial Stewardship
Slide 19
ASP Antimicrobial Stewardship recommended by: CDC, IDSA, SIS,
AAP, PIDS
Slide 20
establish compelling need and goals senior leadership support
effective local physician champion adequate resources pharmacy
infection prevention & control clinical labs
(microbiology/virology) information technology agreed upon process
and outcome measures Key Elements for Successful ASP
Slide 21
evidence based empiric tx early/aggressive tx narrow when
organism isolated stop if infection unlikely limit duration for
established infections based upon current evidence Principles of
Judicious Antimicrobial Use
Slide 22
Blast them: use > 1 antimicrobial to prevent the emergence
of resistance Fool them Antibiotic cycling or rotation Multi-drug
resistance and ability of antibiotics to cross select resistance
Stop irritating them reduce our antibiotic use to the bare minimum
necessary to safely treat our patients Rice LB. CID 2008 Antibiotic
Strategies to Reduce Antibiotic Resistance
Slide 23
Knowledge about duration of therapy limited Travelers diarrhea:
recommendation is for 3 days (but 1 d appears equally effective)
UTI in young females: 1-3 days Community-acquired pneumonia Minimum
of 5 days, afebrile for 48-72 hours, clinically stable
Intra-abdominal infection 5-7 days Rice LB, CID 2008 Shorter
Durations of Therapy
Slide 24
RR 2.8 (95% CI 2.1-3.8) RR 1.7 (95% CI 1.3-2.1) RR 0.2 (95% CI
0.1-0.4) Fishman N. Am J Med. 2006;119(6 suppl 1):S53-S61. ASP
Improves Clinical Outcomes
Slide 25
RR 2.8 (95% CI 2.1-3.8) RR 1.7 (95% CI 1.3-2.1) RR 0.2 (95% CI
0.1-0.4) Fishman N. Am J Med. 2006;119(6 suppl 1):S53-S61. ASP
Saves Money Annual savings (600 interventions/month)
Antibiotics:$302,400.00 Infx-assoc costs: $533,000.00 Total costs:
$4,277,000.00
Slide 26
Depicts the logistics of the prospective-audit-with-feedback
antimicrobial stewardship program developed and implemented at
Children's Mercy Hospitals and Clinics. Stach L M et al. J Ped
Infect Dis 2012;1:190-197 The Author 2012. Published by Oxford
University Press on behalf of the Pediatric Infectious Diseases
Society. All rights reserved. For Permissions, please e-mail:
[email protected]
Slide 27
Positive and negative feelings of clinicians regarding the
antimicrobial stewardship program. Stach L M et al. J Ped Infect
Dis 2012;1:190-197 The Author 2012. Published by Oxford University
Press on behalf of the Pediatric Infectious Diseases Society. All
rights reserved. For Permissions, please e-mail:
[email protected]
Slide 28
Perceived Barriers to Implementation, Development and
Improvement of an Antimicrobial Stewardship Program (ASP) No. (%)
of respondents Barrier With Current ASP (n=45) Planning ASP (n=25)
No plans For ASP (n=68) Any*36 (80)25 (100)59 (87) Loss of
prescriber autonomy14 (31)14 (56)23 (34) Lack of funding*14 (31)18
(72)35 (51) Lack of time*16 (36)17 (68)36 (53) Administration not
aware of ASP value10 (22)10 (40)17 (25) *p
CLABSI: Tx compliance EMPIRIC TX = at or above target = within
15% of Target = >15% from Target PATHOGEN TARGETED DEFINITIVE TX
DURATION of TX
Slide 34
BSI = at or above target = within 15% of Target = >15% from
Target PATHOGEN TARGETED: CA PATHOGEN TARGETED: HA EMPIRIC TX
Slide 35
Cost Savings: $714,463 Pharmacy subgroup including ASP - Supply
Chain Cost Revision team FY10
Slide 36
Topics The case for Antimicrobial Stewardship Define and
Discuss Data for ASPs Examples of Stewardship: MEASUREMENT
Slide 37
Seattle Oakland Palo Alto Madera Los Angeles Orange San Diego
Phoenix Denver Dallas Fort Worth Corpus Christi Houston Little Rock
New Orleans Birmingham Memphis Nashville Atlanta St. Petersburg
Miami Boston Hartford New York Philadelphia DC Norfolk Pittsburgh
Dayton Columbus Cincinnati Akron Buffalo Milwaukee Chicago St.
Louis Detroit Indianapolis Minnesota Omaha Kansas City PHIS
Hospitals How do we Benchmark use?
Slide 38
Benchmarking Antibiotic Use: CHA Hospitals Gerber et al.
Pediatrics 2010
Slide 39
Antibiotic Use at Childrens Hospitals, by Service Line
Slide 40
Variability of Antibiotic Use Across Hospitals, Top Four
APR-DRGs Each circle represents one hospital. Size of circles
corresponds to number of discharges with diagnosis receiving
antibiotics. Red lines represent median values. Broad-spectrum
anti-MRSA coverage: vancomycin, linezolid, tigecycline, daptomycin
Broad-spectrum anti-pseudomonal coverage: imipenem, meropenem,
cefepime, piperacillin, ticarcillin, piperacillin-tazobactam,
ticarcillin-clavulanate, ceftazidime
Slide 41
CHOP ASP: Intranet Site
Slide 42
Implementation of a CAP Guideline Newman RE et al. Pediatrics
2012
Slide 43
Topics The case for Antimicrobial Stewardship Define and
Discuss Data for ASPs Examples of Stewardship: SURGERY
Slide 44
Antibiotic Use at Childrens Hospitals, by Service Line
Slide 45
Slide 46
surgical AMP is used to reduce the microbial burden of skin
colonization that may contribute to intraoperative contamination 2
nd most common Healthcare Associated Infection (HAI) SSIs cause
harm, prolong hospitalizations, can cause readmissions, and can
increases mortality rate Prophylaxis; not treatment When
appropriately used, AMP reduces SSI rate by 50-70% Surgical
Antimicrobial Prophylaxis
Slide 47
PREoperative INTRAoperative POSToperative Prevent Surgical Site
Infections identify MRSA (MDRO) home baths (+/- CHG) choice of
antiseptic periop antibiotics temperature/glucose hand hygiene
wound assessment approp. hair removal temperature/glucose dressing
changes room traffic skin colonization environment physiology wound
care physiology surgical technique Prevent SSI: Driver Diagram
Slide 48
I. Clean: An uninfected operative wound in which no
inflammation is encountered and the respiratory, alimentary,
genital, or uninfected urinary tracts are not entered II.
Clean-Contaminated: Operative wounds in which the respiratory,
alimentary, genital, or urinary tracts are entered under controlled
conditions and without unusual contamination III. Contaminated:
Open, fresh, accidental wounds; operations with major breaks in
sterile technique or gross spillage from GI tract, and incisions in
which acute, nonpurulent inflammation is encountered IV. Dirty or
Infected: Includes old traumatic wounds with retained devitalized
tissue and those that involve existing clinical infection or
perforated viscera Surgical Wound Classes
Slide 49
Goal is to have peak antibiotic serum/tissue levels at the time
of incision. Therefore, complete antibiotic infusion 0 - 60 minutes
prior to incision Start 0-60 minutes prior to incision for agents
with brief infusion times Start 60-120 minutes prior to incision
for vancomycin and fluoroquinolones For longer procedures or with
excessive blood loss, antibiotic(s) may require intraop re-dosing
Antimicrobial Prophylaxis: Timing
Slide 50
Slide 51
Staphylococcus aureus is most common cause of SSI Cefazolin has
activity against most strains of S. aureus; therefore, Cefazolin is
the empiric choice for most procedures However, Cefazolin may not
always be the appropriate choice 1.procedures involving organs with
alternate or additional colonizing bacteria (e.g. GI tract)
2.patients with cephalosporin allergy 3.patients known to be
colonized with resistant bacteria Antimicrobial Choice
Slide 52
Recommendations for choice, timing, dose, and re-dose timing of
AMP for children are available on CHOP intranet and in all ORs
http://intranet.chop.edu/sites/anti microbial/periop-antibiotic-
prophylaxis.html Please call the CHOP Antimicrobial Stewardship
Program, pager 10201, with any questions
SurgeryAntibioticAlternative for Penicillin and/or Cephalosporin
allergy MRSA History of colonization or infection Cardiothoracic
Generalcefazolinclindamycinvancomycin 1 + cefazolin High-risk
implants (pacemaker, ICD, L- VAD) vancomycin + cefazolin vancomycin
+ gentamicinvancomycin 1 + cefazolin Lung transplanttargeted
therapy 2 vancomycin 1 + targeted therapy 2 Gastrointestinal
Appendectomy 3 ceftriaxone + metronidazole ciprofloxacin +
metronidazole vancomycin 1 + ceftriaxone + metronidazole
Esophageal, gastroduodenal, jejunal cefazolinclindamycin +
gentamicinvancomycin 1 + cefazolin Colorectal 3 ceftriaxone and
metronidazole ciprofloxacin + metronidazole vancomycin 1 +
ceftriaxone + metronidazole Liver transplantpiperacillin/tazobac
tam ciprofloxacin + metronidazole vancomycin 1 +
piperacillin/tazobactam NECpiperacillin/tazobac tam nonevancomycin
1 + piperacillin/tazobactam Biliary tract Open and laparoscopic
procedures cefazolinclindamycin + gentamicinvancomycin 1 +
cefazolin Head and Neck Cleannone With implantcefazolinclindamycin
+ gentamicinvancomycin 1 + cefazolin
Clean-contaminatedcefazolinclindamycin + gentamicinvancomycin 1 +
cefazolin Obstetric or Gynecologic Cesarean sectioncefazolin or
cefoxitin clindamycin + gentamicinvancomycin 1 + cefazolin
Orthopedic Generalcefazolinclindamycinvancomycin 1 + cefazolin
High-risk implants (spinal rods, VEPTR) vancomycin + cefazolin (+/-
gentamicin) 4 vancomycin + gentamicinVancomycin 1 + cefazolin (+/-
gentamicin) 4 Neurosurgery cefazolinvancomycinvancomycin 1 +
cefazolin Urologic Generalcefazolinclindamycin +
gentamicinvancomycin 1 + cefazolin Cystourethroscopytargeted
therapy 5 vancomycin 1 + targeted therapy 5 Antimicrobial
Selection: Using CHOP Guidelines
antimicrobial tx of established infection should be limited to
47 days, unless difficult to achieve adequate source control
Intra-abdominal Infections: duration
Slide 61
acute appendicitis without evidence of perforation, abscess, or
local peritonitis requires only prophylactic administration of
narrow spectrum regimens; treatment should be discontinued within
24h Intra-abdominal Infections: prophylaxis
Slide 62
Topics The case for Antimicrobial Stewardship Define and
Discuss Data for ASPs Examples of Stewardship: PRIMARY CARE
Slide 63
Antimicrobial Stewardship Programs recommended for hospitals
most antibiotic use (and misuse) occurs in the outpatient setting
is outpatient stewardship achievable? Antimicrobial
Stewardship
Slide 64
5 urban, academic 24 private practices urban, suburban, rural
common EHR Study Setting: CHOP Care Network
antibiotic prescribing at sick visits varies significantly
across practice sites broad-spectrum antibiotic prescribing at sick
visits varies significantly across practice sites adherence to
prescribing guidelines for AOM, sinusitis, GAS pharyngitis, and pna
varies significantly across practice sites Summary: Outpatient
Variability
Slide 69
cluster-randomized controlled trial bundled intervention vs. no
intervention unit of observation will be the practitioner but
randomized at practice level natural distribution of physicians
avoids intra-practice contamination Study Design
Slide 70
1.guideline development 2.education 3.prescribing audit and
feedback Intervention
Slide 71
5 urban, academic 24 private urban suburban rural Study
Setting: CHOP Care Network
Slide 72
VIRAL common cold URI acute bronchitis tonsillitis pharyngitis
(non-strep) VIRAL common cold URI acute bronchitis tonsillitis
pharyngitis (non-strep) no antibiotics BACTERIAL acute sinusitis
Strep pharyngitis pneumonia BACTERIAL acute sinusitis Strep
pharyngitis pneumonia penicillin/amoxicillin Outcomes
Slide 73
ICD9 codes for common infections (+/- GAS testing, antibiotic
use) verified by chart review and provider feedback Excluding:
antibiotic allergy visit within prior 3 months with antibiotic
concurrent bacterial infection AOM, SSTI, UTI, lyme, acne, chronic
sinusitis, mycoplasma, scarlet fever, animal bite, proph, oral
infections, pertussis, STD, bone/joint children with complex
chronic diseases Case Definitions
Slide 74
12 months of audit/feedback 12 months after feedback ends 12
months baseline data Site presentation Feedback reports
Intervention: Timeline
Broad-Spectrum for Specific Diagnoses Excluding: preventive
visits, CCC, antibiotic allergy, prior antibiotics Standardized by:
age, sex, age-sex, race, Medicaid
Slide 78
History of Antimicrobial Use 1940 A.D. That potion is snake
oil. Here, take this penicillin; its a miracle drug. 1985 A.D.
Penicillin is worthless. Here, take this new antibiotic; its bigger
and better. 2000 A.D. Those antibiotics dont work any more. Here
eat this root. 2000 B.C. Here, eat this root. 1000 A.D. That root
is heathen. Here, say this prayer. 1850 A.D. That prayer is
superstition. Here, drink this potion. History of Antimicrobial
Use
Slide 79
ASPs improve outcomes, reduce use, and save money. Probably
reduce resistance. ASP requires coordinated team effort,
administrative support, and DATA Pediatric surgery and primary care
are potential targets for ASP; look at the data Summary/Future
Directions
