Antibiotic Resistance and Its Relationship to Antibiotic Use
Antimicrobial stewardship in managing septic patients...Recurrent fever Restart of antibiotic ts...
Transcript of Antimicrobial stewardship in managing septic patients...Recurrent fever Restart of antibiotic ts...
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November 11, 2017
Samuel L. Aitken, PharmD, BCPS (AQ-ID)
Clinical Pharmacy Specialist, Infectious Diseases
Antimicrobial stewardship in managing septic patients
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MD Anderson
Conflict of interest statement
I have no conflicts of interest relevant to the content of this presentation
Advisory boards within the last 12 months
• The Medicines Company
• Zavante Therapeutics
• Achaogen
• Melinta
Current / pending research support
• Merck
• The Medicines Company
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MD Anderson
Objectives
1. Identify when and why to de-escalate antibiotics in critically ill
patients
2. Discuss methods for incorporating antimicrobial stewardship
in the ICU
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MD Anderson
The guideline-driven approach to antimicrobials
Selection
• …recommend empiric broad-spectrum therapy with one or more antimicrobials
(strong, moderate)
• …recommend against combination therapy for the routine treatment of
neutropenic sepsis/bacteremia (strong, moderate)
De-escalation
• …recommend that empiric antimicrobial therapy be narrowed once pathogen
identification and sensitivities are established and/or adequate clinical
improvement is noted (BPS)
• …recommend de-escalation…within the first few days in response to clinical
improvement…this applies to both targeted…and empiric combination therapy
(BPS)
• …recommend daily assessment for de-escalation (BPS)
Rhodes S, et al. Crit Care Med 2017;45(3):486-552
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MD Anderson
Commonly used synonyms for de-escalation:
• Narrowing
• Streamlining
• Reducing
How I prefer to think of de-escalation:
• Targeting specific organisms
• Stopping unnecessary drug therapy
• One component of antimicrobial stewardship programs
De-escalation does not have a consistent definition
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MD Anderson
Rationale for broad-spectrum
antimicrobial use
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MD Anderson
Early initiation of appropriate antibiotics determines
mortality in septic patients
• Treatment directed at the likely pathogen and resistance pattern is essential
Kumar A, et al. Chest 2006;34(6):1589-96
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MD Anderson
Four primary pathogens account for half of
microbiologically-confirmed sepsis
Kumar A, et al. Chest 2009;136(5):1237-48
21.4
14.7
7.7 7.3
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E. coli S. aureus K. pneumoniae P. aeruginosa
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fectio
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• Primary pathogen identified in 71% of all cases of sepsis
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MD Anderson
Just how common is antibiotic resistance in the ICU?
• Antibiotic resistance is not as common as we think at a national level
• Resistant organisms still must be considered in empiric therapy
Sader HS, et al. Diagnostic Microbiol Infect Dis 2014;78:443-8
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MD Anderson
Like politics, all resistance is local
• Site-specific antibiograms are frequently different than national averages
• Local epidemiology is key to rational antimicrobial selection
Aitken SL. Unpublished data
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MD Anderson
Why is antibiotic de-escalation and
discontinuation important?
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MD Anderson
Definitive combination therapy with aminogylcosides for
bacteremia likely does more harm than good
• Nephrotoxicity 64% lower in monotherapy group (number needed to harm: 15)
• Similar results seen in pediatric patients
Paul M,, et al. BMJ 2004;328(7441):668Tamma PD, et al. JAMA Pediatr 2013;167(10):903-10
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MD Anderson
Combination therapy is no better as definitive therapy
even for P. aeruginosa infections
• Other studies show no benefit of definitive combination therapy in P. aeruginosa
ventilator-associated pneumonia
• Role of combination empiric therapy is still being debated
Paul M, et al. Clin Infect Dis 2013;57(2):217-20Garnacho-Montero J, et al. Crit Care Med 2007;35(8):1888-95
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MD Anderson
Vancomycin and piperacillin-tazobactam are
synergistically nephrotoxic
• Onset of nephrotoxicity is sooner than with vancomycin and other β-lactams
• Limited data in critically ill patients, but overall findings are similar
• Critically ill pediatric patients also see increased nephrotoxicity
Luther M, et al. Crit Care Med 2017;ePub ahead of print (Oct. 28)Holsen MR, et al. Pediatr Crit Care Med 2017;ePub ahead of print (Sep. 12)
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MD Anderson
C. difficile risk increases with cumulative antibiotic use
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Duration of antibiotic therapy
CDI Cases Non-CDI Controls
Stevens V, et al. Clin Infect Dis 2011;53(1):42
• Cumulative number of antibiotics used also increases CDI risk
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0 days 1 - 3 days 4 - 21 daysPerc
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xposure
Duration of prior imipenem exposure
Colonized Non-colonized
Prolonged carbapenem use leads to colonization with
carbapenem-resistant Gram negatives
• Majority of resistance occurred through non-transmissible mechanisms
Armand-Lefèvre, et al. Antimicrob Agents Chemother 2013;57(3):1488-95
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MD Anderson
Infection with resistant organisms is a predictable
consequence of prolonged antibiotic use
Percent with prior receipt of antibiotics
MDR
P. aeruginosa
No MDR
P. aeruginosa
p-value
Carbapenem, > 3 days 27 13 0.002
Fluoroquinolone, > 4 days 27 13 0.001
Aminoglycoside, >5 days 32 16 <0.001
Cefepime, > 9 days 16 5 0.001
Pip-tazo, > 12 days 34 17 <0.001
MDR – multidrug resistant
• If antibiotics aren’t needed, stop them as soon as possible
• “Just in case” can have serious consequences down the road
Lodise TP, et al. Antimicrob Agents Chemother 2007;51(2):417-22Lodise TP, et al. Infect Control Hosp Epidemiol 2007;28(8):959-65
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MD Anderson
But is antibiotic de-escalation actually safe in the ICU?
• All studies performed to this point have major bias
• The data on downstream development of resistance are terrible
Tabah A, et al. Clin Infect Dis 2016;62(8):1009-17
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MD Anderson
How can stewardship be successfully
implemented in the ICU?
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MD Anderson
The key to stewardship is a team-based approach
The patient!
Critical care
Infectious diseases
Antimicrobial stewardship
Clinical microbiology
Informatics
Infection control
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MD Anderson
The MD Anderson approach to stewardship - ABX
Targeted antibiotics
Daptomycin
Linezolid
Meropenem
Tigecycline
Vancomycin
Ceftazidime-avibactam
Ceftolozane-tazobactam
Targeted services
Leukemia
Stem cell transplantation
Lymphoma / myeloma
All ID consultant services
Aitken SL, ICAAC 2015Tverdek FP, et al. J Antimicrob Stewardship 2017; in press
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MD Anderson
A completely passive email reduces antibiotic use
Aitken SL, ICAAC 2015Tverdek FP, et al. J Antimicrob Stewardship 2017; in press
• No active enforcement or verification of responses
• Semi-regular compliance summaries provided at the departmental level
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MD Anderson
Time for a time-out?
• Anyone on the team can do a checklist assessment
• Can easily be customized to meet your needs
Aitken SL, ECCMID 2016
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MD Anderson
Antibiotic checklists are safe and effective
1.4
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Admit to ICUwithin 7 days
Newdocumented
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Recurrent fever Restart ofantibiotic
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Checklist Historic controls
p = 0.50 p = 0.62 p = 0.57 p = 0.62
• Antibiotic discontinuation rate at day 3 increased from 56% to 73% with checklist
• Required active maintenance and “nudging” to force use
Aitken SL, ECCMID 2016
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MD Anderson
• Broad-spectrum antibiotics frequently are not needed
• Prolonged use of any antibiotic can have serious downstream
consequences
• De-escalation may help prevent some of these bad outcomes
• Stewardship needs to be individualized to the patient and the hospital
Conclusions
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MD Anderson
The MDACC Antimicrobial Stewardship Team
• Micah Bhatti
• Farnaz Foolad
• Pat McDaneld
• Frank Tverdek
• Victor Mulanovich
Acknowledgements
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November 11, 2017
Samuel L. Aitken, PharmD, BCPS (AQ-ID)
Clinical Pharmacy Specialist, Infectious Diseases
Antimicrobial stewardship in managing septic patients