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Antimicrobial Stewardship
and Infection Prevention:
A Critical Connection
October 30, 2014
Anurag Malani, M.D.
Medical Director, Infection Prevention and
Antimicrobial Stewardship Programs
St. Joseph Mercy Health System
Adjunct Assistant Professor, University of Michigan
Outline
Reasons for urgency of Antimicrobial
Stewardship Programs (ASPs)
Understand the purpose, goals, and
provide overview of an ASP
Describe ASPs in key settings
Summary and case studies
What is Antimicrobial Stewardship?
“The selection of the optimal antimicrobial
agent, route of administration, dose, and
duration to provide maximal clinical
benefit, while minimizing unintended
consequences.”
Why Antimicrobial Stewardship?
 Up to 50% of abx use is inappropriate
 High quantity, poor quality
 Inappropriate & unnecessary abx use can lead
to selection of resistant pathogens
 Antimicrobial resistance continues to increase
 Emergence of antimicrobial resistance leads to
significant impact on pt morbidity & mortality,
health care costs
Dellit TH, et al. Clin Infect Dis 2007;44:159-77
Why Antimicrobial Stewardship in
Long Term Care?
 Implementation of ASP in LTCF has been limited
 U.S. population continues to age
 Estimated 21% of population in 2040 > 65 y
 More than 15,000 nursing homes
 High prevalance of colonization and infection
with MDRO
 Failure to control abx use in LTCF can also
affect surrounding hospitals
Rhee S, et al. Infect Dis Clin N Am 2014;28:237-46
How We Acquire Antibiotic Resistant
Organisms in Hospitals
Paterson DL. Clin Infect Dis 2006;42:S90-5
Resistance: A Public Health Crisis
www.cdc.gov/drugresistance/healthcare
Antimicrobial Resistance Continues to Increase
Wenzel et al. Infect Cont Hosp Epi 2008;29:1012-8
Emergence of KPC Infections
Urine Culture Result Positive for CRE
KPC-producing CRE in the U.S. - 2014
http://www.cdc.gov/hai/organisms/cre/TrackingCRE.html
Trends of Multi-drug Resistant Organisms
Antibacterials Approved by the FDA, 1983 - 2007
Spellberg B et al. Clin Infect Dis. 2008;46:155-164
Impending Crisis of New Antibiotics
Last new class of drugs active against
GNB, in the 1970s, – “Trimethoprim”
No new classes of antimicrobials in the
foreseeable future
No new drugs to deal with multiresistant GNB until 2018
WHO – “Antibiotic resistance” as one of
major threats to human health
1. Bartlett J. Clin Infect Dis 2011;53:S4.
2. http://www.ecdc.europa.eu/en/publications/Publications/Forms/ECDC_DispForm.aspx?ID=444.
Evolving Resistance,
The“ESKAPE” Organisms
Enterococcus faecium
Staphylococcus aureus
Klebsiella pneumoniae
Acinetobacter baumannii
Pseudomonas aeruginosa
Enterobacter species
Bartlett J. Clin Infect Dis 2011;53:S4.
.
Controlling Resistance?
A combination of BOTH
Effective antimicrobial stewardship
program
AND
Comprehensive infection control program
Have been shown to limit the emergence
and transmission of antibiotic resistant
bacteria
Dellit TH, et al. Clin Infect Dis 2007;44:159-77
Antimicrobial Stewardship Works
Impact of a Reduction in the Use of High-Risk Antibiotics on the Course of an Epidemic of
Clostridium difficile-Associated Disease Caused by the Hypervirulent NAP1/027 Strain
Valiquette L, et al. Clin Infect Dis 2007;45:112-121
Antimicrobial Stewardship Reduces Costs
Standiford H, et al. Infect Cont Hosp Epi 2012;33:338-46.
Clinical outcomes better with
antimicrobial stewardship program
Fishman N. Am J Med. 2006;119:S53.
Antimicrobial Stewardship Program Goals
 Ensure appropriate antimicrobial use
- Optimal selection, dose, duration
 Reduce or attenuate advancing antimicrobial
resistance
 Improve patient outcomes and reduce adverse
events related to antimicrobials
- Decrease Clostridium difficile infection
- Decrease morbidity and mortality
- Decrease length of stay
 Decrease healthcare expenditures and antimicrobial
costs
Dellit TH, et al. Clin Infect Dis 2007;44:159-77
Ohl CA. Seminar Infect Control 2001;1:210-21
Antimicrobial Stewardship Interventions
 Prospective audit with intervention and
feedback
 Formulary restriction and preauthorization
 Educations
 Streamlining and de-escalating
 Dose optimization
 Guidelines and clinical pathways
 Parenteral to oral conversion
Dellit TH, et al. Clin Infect Dis 2007;44:159-77
Antimicrobial Stewardship Partners
Information Technology
ID Physicians &
Fellows
Pharmacy and
Therapeutics
Committee
Abx Subcommittee
Clinical Pharmacists
Antimicrobial
Stewardship Team
Clinicians & Residents
Administration
Infection Control
Microbiology Lab
SJMAA Antimicrobial Stewardship
Program
 Focus on restricted abx
- New starts, duration
 Interventions
- Approve
- Stop abx
- Change/Narrow abx
- Obtain ID Consult
- Against ASP advice
SJMAA Antimicrobial Stewardship Program
Outcomes from SJMAA ASP (2009-10)
Demographic and clinical characteristics and outcomes
of patients pre-ASP compared to patients post-ASP
Multivariable analysis for association of ASP
and patient outcomes
Malani AN, et al. Am J Infect Control 2013;41:145-8.
Flow Diagram of Outcomes from ASP
Malani AN, et al. Am J Infect Control 2013;41:145-8.
Antimicrobial Costs by Fiscal Year
FY 2009 FY 2010 FY 2011 FY 2012
Percent
Change
Antimicrobial
agents total costs
1,503,748
1,274,837
1,231,079
1,221,275
-18.8
(-784,053)
Total patient days
147,955
144,783
146,332
146,310
Antimicrobial
costs per patient
day (average)
10.16
8.81
8.41
8.35
-17.8
462,404
297,851
278,998
342,997
-25.8
(-467,360)
Targeted
antimicrobial
agents
Annual Mortality Rate
per Million Population
# of CDI Cases per 100,000 Discharges
Incidence and mortality of CDI
are increasing in US
1. Elixhauser A, et al. Healthcare Cost and Utilization Project: Statistical Brief #50. April
2008. Available at: http://www.hcup-us.ahrq.gov/reports/statbriefs/sb50.pdf.
2. Redelings MD, et al. Emerg Infect Dis. 2007;13:1417-1419.
National Efforts on Antimicrobial
Stewardship
 SHEA Task Force
 IDSA and PIDS
 CDC Get Smart Campaign – Core Elements
www.cdc.gov/getsmart/
 JTC National Patient Safety Goals
(NPSG) 07.03.01
 California Senate Bill 739
 22% of 135 surveyed CA hospitals influenced to
initiate an ASP
Trivedi K, Rosenberg J. Infect Cont Hosp Epi 2013;34:379-84.
Role of the Infection Preventionist
Daily activities of IPs/HEs vital for ASP
Implementation of evidenced-based
practice and prevention care bundles
(hand hygiene, isolation precautions,
environmental cleaning, etc)
No transmission of infection = Avoidance
of abx
Role of the Infection Preventionist
 Identification and surveillance of MDROs
 Monitoring and reporting of trends of MDROs
 Promote high compliance with hand hygiene
 Track and analyze trends in antimicrobial
resistance
 Educate multidisciplinary rounding teams about
NHSN surveillance definitions of HAIs
 Partners for accountability – share findings with
and progress to stakeholders and providers
Moody J, et al Infect Cont Hosp Epi 2012;33:328-30.
Barriers for Antimicrobial Stewardship
in Long Term Care
 Limited staffing and infrastructure
 Having clinical providers off-site
 Decision-making based on communications from
front-line staff
 Limited diagnostic testing on-site leads to delays
in obtaining, processing, and specimen results
Trivedi K, et al. Infect Dis Clin N Am 2014;28:281-89.
Recommendations for Antimicrobial
Stewardship in Long Term Care
 Composition of ASP team are different
 Staff pharmD, IP, Administration – Med. Director,
DON, rep. from nursing/medical staff
 When available: ID physician (telemedicine)
 Development of ASP in settings with limited
resources should be approached as “menu of
interventions and strategies”
 Successful ASPs have been implemented in
variety of nonuniversity settings
Trivedi K, et al. Infect Dis Clin N Am 2014;28:281-89.
Strategies for Antimicrobial
Stewardship in Long Term Care
 Education – complete ASP educational offering
 Incorporate high-abx prescribing disciplines in
ASP (i.e. hospitalist)
 Use nonphysician HCP as extenders of ASP
 Develop, calculate, track basic metrics
 Antimicrobial cost/pt day
 MDRO and CDI trends
 Prepare an annual antibiogram
 Allow pharmacy to make automatic conversions
(IV to PO; dosing: aminoglycoside/vanc,renal)
Trivedi K, et al. Infect Dis Clin N Am 2014;28:281-89.
Strategies for Antimicrobial
Stewardship in Long Term Care
 Incorporate evidenced-based guidelines into
order sets and protocols
 Loeb criteria proposed to improve abx use
 McGeer criteria – surveillance definitions in LTCF
Trivedi K, et al. Infect Dis Clin N Am 2014;28:281-89.
How to start Antimicrobial Stewardship
in Long Term Care
 Identify all interested parties
 Buy-in from administration
 Medical director, DON
 Understand current institutional approaches for
treating infectious disease syndromes
 Identify physician champions
 Target 2 to 4 abx-related issues
 Formulary restriction, etc
Trivedi K, et al. Infect Dis Clin N Am 2014;28:281-89.
Stewardship at Transitions of Care
 All pts to get parenteral abx seen by ID
prior to d/c at Cleveland Clinic
 244 CoPat consultations
 175 (72%) approved
 66 (28%) avoided
 11% consults avoided abx
 Targeting pts at transitions of care
(hospital to community) is an AS strategy
Shrestha , et al Infect Cont Hosp Epi 2012;33:401-04.
Current State of Stewardship at SJMAA
 Track all restricted antimicrobials
 Track all antimicrobials in high risk pts
 Use software for surveillance, tracking, clinical
decision support
 Development of bundles for specific
infections/syndromes
 Use of antimicrobial timeouts and rapid
diagnostic testing
 Lead quality initiatives related to abx use (i.e.
SCIP)
Surgical Care Improvement Project (SCIP)
Infection-Prevention Measures
1. Stulberg JJ, et al. JAMA 2010;303:2479-2485.
2. File T, et al. Clin Infect Dis. 2011;53:S15-22.
Clostridium difficle Infection Powerplan
Antimicrobial Management Page
Summary
 Primary mission of ASPs is patient safety
 Goals of ASPs are to ensure that there are
systems and support to help providers use
antibiotics optimally
 ASPs can improve pt outcomes, reduce tx
costs, reduce CDI, & reduce or slow the
development of resistant organisms
 ASPs can and must be implemented across
continuum of care
Case # 1
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49 y/o F, hx of Downs
Recurrent hospitalizations, most recently 1 wk prior
Hx of recent clogging of J-tube
No fevers
WBC 4.5
U/A shows + LE, + nitrites, 10 WBC
Urine cx shows MDRO
Case # 1
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49 y/o F, hx of Downs
Recurrent hospitalizations, most recently 1 wk prior
Hx of recent clogging of J-tube
No fevers
WBC 4.5
U/A shows + LE, + nitrites, 10 WBC
Urine cx shows MDRO
* Final Report *
URINE CULTURE + SUSCEPTIBILITY
Source: URINE
Collected: 04/17/11 1219
--------------------------------------------Culture (Final)
COLONY COUNT: >100,000 CFU/ML
Escherichia coli
THIS ORGANISM PRODUCES AN EXTENDED SPECTRUM BETALACTAMASE (ESBL). IT SHOULD BE REGARDED AS RESISTANT
TO ALL CEPHALOSPORINS, REGARDLESS OF THE RESULTS OF
ROUTINE SUSCEPTIBILITY TESTING.
E.coli
______
MIC 0006054646
___ __________
AMIKACIN
AMPICILL/SULBAC
AMPICILLIN
AZTREONAM
CEFAZOLIN
CEFEPIME
CEFTRIAXONE
CIPROFLOXACIN
ERTAPENEM
ESBL
GENTAMICIN
MEROPENEM
NITROFURANTOIN
TOBRAMYCIN
TRIMETH-SULFA
>=16
4
>=32
>=32
>=64
>=64
16
>=64
>=4
<=0.5
POSITIVE
>=16
<=0.25
<=16
S
R
R
R
R
R
R
R
S
>=320
R
R
S
S
R
Case # 1
Start Ertapenem.
B. Start Amikacin.
C. Start Meropenem.
D. No treatment.
A.
Case # 1
Take Home Points
 No need to treat asymptomatic bacteriuria
- No urinary tract signs or symptoms
- Typical pathogens (not contaminants)
- Urine appropriately collected
Treatment of Positive Urine Cultures in Hospitalized Patients:
A Key Driver of Inappropriate Antimicrobial Use – SJMH AA
145 patients with a positive urine culture,
defined by having any growth of bacteria or
yeast on a urine culture
75 had a UTI based on
guideline review
70 with
asymptomatic
bacteriuria
43 treated
for a UTI
27 not treated for
a UTI
Treatment of Positive Urine Cultures in Hospitalized Patients:
A Key Driver of Inappropriate Antimicrobial Use – Livingston
145 patients with a positive urine culture,
defined by having any growth of bacteria or
yeast on a urine culture
88 had a UTI based on
guideline review
57 with
asymptomatic
bacteriuria
37 treated
for a UTI
20 not treated for
a UTI
Case # 2
 83 year old male s/p AAA repair
 Extubated in PACU and tx to the 2000 unit
 4 days later, develops respiratory distress, SICU
tx, and reintubation.
 Further evaluation:
New infiltrate on CXR
WBC 26.5
Tmax 101.9
Case # 2
 Started on Cefepime and Vancomycin.
Has PCN allergy (rash).
 After 1 wk, WBC decreased to 13.7
 Final culture & sensitivities from sputum show:
 Direct Smear: Moderate neutrophils, GNB
Culture (Final): Enterobacter aerogenes
Enterobacter aerogenes
Ampicillin/Sulb
Ampicillin
Aztreonam
Cefazolin
Cefepime
Ceftriaxone
Ciprofloxacin
Gentamicin
Meropenem
Piper/Tazobac
Tobramycin
Trimeth-Sulfa

MIC
INT
8
16
<=1
>=64
<=1
<=1
<=0.25
<=1
<=0.25
<=4
<=1
<=20
R
R
S
R
S
S
S
S
S
S
S
S
Case # 2
 Pt received 72 hours of Cefepime/Vancomycin
 Readdress abx regimen given cx results
Continue Cefepime and Vancomycin
B. Continue Cefepime. D/C Vancomycin.
C. De-escalate Cefepime to a different abx. D/C
Vancomycin.
A.
Case # 2
Take Home Points
 Antibiotic Timeout (reasons for abx use)
 Streamlining and de-escalating
 Duration for abx course
 Clear plans when transitions of care (tx to/from
ICUs/discharge summaries/ECFs)
Case # 3
Case # 3
 88 y/o male, hx of dementia, presented with
confusion/weakness
 Recent stay at an ECF, presented with foley
 WBC 13.4
 Started on Ceftriaxone  Cefepime/Vancomycin
 Blood cx: ¾ CNS
 Urine cx: alpha hemolytic streptococcus
 U/A 57 WBC, + LE
Case # 3
 No fevers, exam significant for L knee
effusion/pain
 ID c/s stopped all abx
 Underwent arthrocentesis  Pseudogout
 A few days later, started on IV flagyl for CDI
 Changed over to PO flagyl
 D/C back to ECF
Case # 3
 While at ECF, receives ertapenem for ESBL
E. Coli bacteriuria, and then nitrofurantoin for
VRE bacteriuria
 Presents 1 month from previous admission with
abdominal pain, diarrhea, lethargy, WBC 15.9
 Started on IV ceftriaxone/flagyl
 Seen by ID
Case # 3
Add po Vancomycin
B. D/C Ceftriaxone, add po Vancomycin.
C. Change abx to Zosyn
D. No treatment
A.
Case # 3
 Severe CDI
 Pt eventually goes on hospice despite maximal
medical tx for a wk
Case # 3
Take Home Points
 Aware of adverse effects of abx including CDI,
MDRO, etc
 Improved abx use improves pt outcomes
 AS through continuum of care is critical