Transcript 2012 ABX Stewardship - EPIC Epidemiologists and Preventionists in

Let’s Really Implement
Antimicrobial Stewardship
Chris Gentry, Pharm.D., BCPS
Clinical Coordinator and
Clinical Specialist, Infectious Diseases
Oklahoma City VA Medical Center
Unintended consequences
• Pt seen for approval of piperacillin/tazobactam, linezolid,
daptomycin.
• 79 yo MALE w/ h/o CKD, CHF, DM originally transferred
from outside hospital 12/31 with ARF, new onset A.fib,
and right pleural effusion.
• Hospital course complicated by development of HCAP,
HIT, NSTEMI, solar keratosis with hemorrhage.
– HCAP treated empirically with pip/tazo 1/12-1/22; no
opportunity to de-escalate due to lack of microbial
etiology necessitating broad-spectrum therapy
Unintended consequences
• Transferred to MICU 1/29 for altered mental status, GPC
bacteremia & presumed nosocomial pneumonia.
• Pip/tazo and ciprofloxacin added to vancomycin.
• Trach aspirate and BAL culture grew a pip/tazo-resistant
Enterobacter cloacae.
• Patient's GPC bacteremia was found to be vancomycinresistant Enterococcus faecium.
– Vancomycin changed to daptomycin & linezolid for
Gram positive bacteremia & pneumonia.
• Patient also has purulent UA with culture growing
Candida albicans.
Unintended consequences
• Recommended dc pip/tazo since E. cloacae was
pip/tazo-resistant. Given good MIC of the E. cloacae to
ciprofloxacin, treated with ciprofloxacin monotherapy,
increasing dose to 400 mg IV q12hr.
• Recommended treating VRE bacteremia with either
linezolid or daptomycin, but not both. In this
circumstance either was appropriate but linezolid has
confirmed activity against this isolate.
• Recommended starting fluconazole for Candida albicans
in urine.
Effect of broad-spectrum antibiotics
on microbial ecosystems
Green = susceptible/nice
Red = resistant/mean
Effect of narrow-spectrum antibiotics
on microbial ecosystems
Light Green = susceptible/nice
Dark Green = resistant/nice
Red = resistant/mean
Inactive pipeline
Lack of unique classes
From: Extendingthecure.org, RW Johnson Foundation, 2007
Gram negative antibiotic pipeline
Gram negative antibiotic pipeline
• Nada
Gram negative antibiotic pipeline
• Nada
• Nothing
Gram negative antibiotic pipeline
• Nada
• Nothing
• Zilch
Gram negative antibiotic pipeline
•
•
•
•
Nada
Nothing
Zilch
Non-existent
Why Antimicrobial Stewardship ?
• Resistant organisms lead to poorer outcomes in
efficacy:
– Vancomycin-resistant enterococci
– Glycopeptide intermediate or resistant
Staphylococcus aureus
– Penicillin-resistant Streptococcus pneumoniae
– Extended-spectrum beta-lactamase producing
Klebsiella pneumoniae and E. Coli
– Multidrug-resistant Acinetobacter sp and
Pseudomonas aeruginosa
– Candidemia
Why Antimicrobial Stewardship ?

Resistant organisms lead to poorer outcomes
in safety, leading to ↑ use of:
•
•
•
•
•
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Aminoglycosides
Carbapenems
Colistin
Linezolid
Voriconazole
Amphotericin
Why Antimicrobial Stewardship ?
• Resistant organisms lead to increased lengths
of stay
Why Antimicrobial Stewardship ?
• Resistant organisms
lead to more broadspectrum antibiotic
use
– Which, in turn, leads
to more resistant
organisms
Multi-drug resistant
Gram negative infections
• ESBL-producing Klebsiella sp. and E Coli
• Acinetobacter sp. and Pseudomonas sp.
– Cases being seen that are PAN-resistant
• Necessitating the rapid increase in use of
carbapenems, tigecycline, and colistin
ICU Gram negative bacilli bloodstream
infections
Wisplinghoff H, et al. Clin Infect
Dis 2004;39:309-317
2009 ICU Gram negative bacilli
susceptibilities
Bertrand, Dowzicky. Clin Ther 2012;34:124-137
ESBL-producing K. pneumoniae and E. Coli
Susceptibility & Resistance Characteristics
• Resistant to:
– All penicillins
• Questionable activity for piperacillin/tazobactam
– First, second and third generation cephalosporins
• Questionable activity for cefepime
– Aztreonam
– Fluoroquinolones
• Susceptibility rates of ~25%
– TMP-sulfamethoxazole
– Aminoglycosides
• Tobramycin and amikacin can be susceptible
ESBL-producing K. pneumoniae and E. Coli
Susceptibility & Resistance Characteristics
• Susceptible to:
– Carbapenems
• Some level of concern for ertapenem
– Tigecycline
– Colistin
ESBL incidence
• Klebsiella sp. ESBL rates increased from ~10%
in 2003 to ~15% thru 2008.
• E.coli ESBL rates increased from ~3% in 2003
to 7% thru 2008
• Proteus mirabilus ESBL rates have been ~4%.
Castanheira M, et al. American Society for Microbiology General Meeting.
May 2010. San Diego, CA
KPCs
Susceptibility & Resistance Characteristics
• Resistant to:
– Penicillins
– Cephalosporins
– Aztreonam
– Carbapenems
• Usually
• Carbapenemase activity may not provide resistance if
other mechanisms are not present
– Fluoroquinolones
• Usually
KPCs
Susceptibility & Resistance Characteristics
• Susceptible to:
– Tigecycline
– Colistin
– Aminoglycosides
MDR P. aeruginosa, Acinetobacter sp.,
and other non-fermenters
MDR P. aeruginosa, Acinetobacter sp.,
and other non-fermenters
• Susceptible to:
– Colistin
• Use with an anti-pseudomonal carbapenem or rifampin
may produce synergistic killing and reduce emergence
of colistin resistance
– Amikacin
– Acinetobacter sp. may be susceptible to:
• Ampicillin-sulbactam
• Minocycline
• Tigecycline
Colistin and Tigecycline
Colistin
Back to the Future
• Polymixin E
– look at your triple antibiotic ointment tube
• 2.5-5 mg/kg/day, divided into 2 or 3 doses
• Revived due to ICU outbreaks of multidrug resistant
P. aeruginosa and Acinetobacter sp. infections
• Should use in combination with carbapenem
or rifampin to minimize emergence of colistin
resistance
• Nephrotoxicity in ~20-30%
• Neurotoxicity (NMB) in ~10%
Tigecycline
• New class: Glycylcycline
– similar to tetracyclines without similar resistance
• Very unique – good AND bad - microbiologic profile
– Gram negative bacilli EXCEPT for:
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•
•
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Pseudomonas aeruginosa
Proteus mirabilus
Providencia sp.
Serratia marcescens
– Gram positive cocci INCLUDING:
• MRSA
• VRE
• MDR Streptococcus pneumoniae
– Anaerobic activity
Tigecycline
• 100 mg IV load, then 50 mg IV q12h
• Very low serum concentrations
– Limits role in serious infections (along with being
bacteristatic)
• Reasonable volume of distribution
• Primarily biliary excreted
– Limits role in UTI’s
• High rate of nausea (20-30%) and vomiting (10%)
– Limited primarily to first couple of days
IDSA/SHEA Guidelines: Executive
Summary
1. Core members of a multidisciplinary antimicrobial
stewardship team include an infectious diseases
physician and a clinical pharmacist with infectious
diseases training (A-II) who should be compensated for
their time (A-III), with the inclusion of..... Because
antimicrobial stewardship, an important component of
patient safety, is considered to be a medical staff function,
the program is usually directed by an infectious diseases
physician or codirected by an infectious diseases
physician and a clinical pharmacist with infectious
diseases training (A-III).
IDSA/SHEA Guidelines: Executive
Summary
2. Collaboration between the antimicrobial stewardship
team and the hospital infection control and pharmacy and
therapeutics committees or their equivalents is essential (AIII).
4. The infectious diseases physician and the head of
pharmacy, as appropriate, should negotiate with hospital
administration to obtain adequate authority, compensation,
and expected outcomes for the program (A-III).
Antimicrobial Stewardship Program:
Personnel
ID MD
Epi
ID PharmD
ASP
IT
ICP
Micro
Pharmacist level of impact
ID-TRAINED
GENERAL
CLINICAL
STAFF
Education
Resistance &
Case-specific expertise
Clinical practice guidelines
IV to PO
Renal dosing
Stewardship Strategies –
Restriction enforcement model
• Preauthorization
• Use of “experts” at
outset of therapy
• May delay initiation of
therapy
• 24/7/365
• unless exceptions
for after-hours are
in place (ie, first
dose sent)
• Prospective audit
• Maintains prescriber
autonomy
• Avoids potential delays
in timely therapy
• Recommendations
may be optional
• By drug, by culture, by
disease state
Stewardship Strategies, cont’d.
• Education
– Not very effective when used alone
• IV to PO
– Traditionally big bang-for-the-buck intervention,
but physicians are doing this better on their own.
• Clinical practice guidelines
– Development
– Dissemination
– Enforcement
– Updating
• Antimicrobial order forms
– Good for initial empiric therapy, but then what?
Stewardship Strategies, cont’d.
• De-escalation
– Most effective with good quality, positive cultures
– What about empiric therapy?
– What if there are no culture data?
• Dose optimization
– Optimizes outcomes?
– Doesn’t alter broad-spectrum activity
• Antimicrobial cycling
– Largely dismissed now, no real effect on resistance
Anti-infective spectrum funnel
Gram positive Gram positive/ Gram negative
Fungal
Meropenem, Imipenem
Daptomycin
Amphotericin
& Doripenem
Linezolid
Telavancin
Piperacillin/tazobactam
Voriconazole
Cefepime & Ceftazidime
Quinopristin/
Posaconazole
Fluoroquinolones
Dalfopristin
Vancomycin
Ertapenem
Ceftriaxone
Echinocandins
Amp/sulbactam
Cefazolin
Cefoxitin
Nafcillin
Itraconazole
Penicillin
Cefazolin
Ampicillin
NONE
Fluconazole
Types of
interventions
Resistance effect Cost
effectiveness
Trade one broad-spectrum Little effect
regimen for another
Little effect
Days 2-3
Narrow the spectrum
based on culture and
susceptibility results
Large effect
Large effect
Days 4-5
Patients doing well;
change to po and/or
discharge
Large effect
Enormous effect
Days 7-14
Patient cured;
discontinue therapy
Large effect
Large effect
Day 1
Antibiotic outcome timeline
Conclusions
• MDR bacteria threaten
our ability to treat
outpatient infections with
oral antibiotics and our
ability to treat inpatient
infections with
intravenous antibiotics
• Totality of evidence
points only to increasing
trends in the prevalence
of MDR bacteria with
current practices
Conclusions, cont’d
• The antibiotics we are forced to use to treat MDR
bacterial infections are:
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–
–
–
limited in number
potentially less effective
generally less safe
generally more broad-spectrum (feeds vicious cycle)
• The antibiotic pipeline looks dismal for the foreseeable
future
• Efforts need to focus on preventing infections and
maximizing the durability of available treatment
options with antimicrobial stewardship.