Let’s Really Implement Antimicrobial Stewardship Chris Gentry, Pharm.D., BCPS Clinical Coordinator...
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Transcript of Let’s Really Implement Antimicrobial Stewardship Chris Gentry, Pharm.D., BCPS Clinical Coordinator...
Let’s Really Implement Antimicrobial Stewardship
Chris Gentry, Pharm.D., BCPSClinical Coordinator and Clinical Specialist, Infectious DiseasesOklahoma 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 vancomycin-
resistant 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/niceRed = resistant/mean
Effect of narrow-spectrum antibiotics on microbial ecosystems
Light Green = susceptible/niceDark Green = resistant/niceRed = 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:• 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 broad-spectrum 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. ColiSusceptibility & 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. ColiSusceptibility & 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
ColistinBack 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:
• 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 stewardshipteam and the hospital infection control and pharmacy andtherapeutics committees or their equivalents is essential (A-III).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
ASP
ID MD
ID PharmD
Micro
IT ICP
Epi
Pharmacist level of impact
Education IV to PO Renal dosing
Clinical practice guidelines
Resistance & Case-specific expertise
STAFF
GENERALCLINICAL
ID-TRAINED
Stewardship Strategies – Restriction enforcement model
• Prospective audit• Maintains prescriber
autonomy• Avoids potential delays
in timely therapy• Recommendations
may be optional• By drug, by culture, by
disease state
• 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)
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 funnelGram positiveGram positive/ Gram negative Fungal
DaptomycinLinezolid Telavancin Quinopristin/ Dalfopristin
Vancomycin
CefazolinNafcillin
Penicillin
Meropenem, Imipenem & Doripenem
Piperacillin/tazobactamCefepime & Ceftazidime
Fluoroquinolones
ErtapenemCeftriaxone
Amp/sulbactamCefoxitin
CefazolinAmpicillin
Amphotericin
VoriconazolePosaconazole
Echinocandins
Itraconazole
FluconazoleNONE
Types of interventions
Trade one broad-spectrum regimen for another
Narrow the spectrum based on culture and susceptibility results
Patients doing well; change to po and/or discharge
Patient cured; discontinue therapy
Resistance effect Cost effectiveness
Little effect Little effect
Large effect Large effect
Large effect Enormous effect
Large effect Large effect
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:– 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.