antimicrobial stewardship in managing septic patients...recurrent fever restart of antibiotic ts...
TRANSCRIPT
November 11, 2017
Samuel L. Aitken, PharmD, BCPS (AQ-ID)
Clinical Pharmacy Specialist, Infectious Diseases
Antimicrobial stewardship in managing septic patients
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
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
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
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
MD Anderson
Rationale for broad-spectrum
antimicrobial use
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
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
0
5
10
15
20
25
E. coli S. aureus K. pneumoniae P. aeruginosa
Pe
rce
nt o
f co
nfirm
ed
in
fectio
ns
• Primary pathogen identified in 71% of all cases of sepsis
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
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
MD Anderson
Why is antibiotic de-escalation and
discontinuation important?
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
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
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)
MD Anderson
C. difficile risk increases with cumulative antibiotic use
0
5
10
15
20
25
30
35
40
< 4 4 - 7 8 - 18 > 18
Perc
en
tage
of
patien
ts
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
MD Anderson
0
10
20
30
40
50
60
70
0 days 1 - 3 days 4 - 21 daysPerc
ent
with a
ntibio
tic e
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
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
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
MD Anderson
How can stewardship be successfully
implemented in the ICU?
MD Anderson
The key to stewardship is a team-based approach
The patient!
Critical care
Infectious diseases
Antimicrobial stewardship
Clinical microbiology
Informatics
Infection control
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
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
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
MD Anderson
Antibiotic checklists are safe and effective
1.4
15.712.9
18.6
3.2
12.7
15.9
19.1
0
5
10
15
20
25
30
Admit to ICUwithin 7 days
Newdocumented
infection
Recurrent fever Restart ofantibiotic
Pe
rce
nt o
f e
ligib
le p
atie
nts
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
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
MD Anderson
The MDACC Antimicrobial Stewardship Team
• Micah Bhatti
• Farnaz Foolad
• Pat McDaneld
• Frank Tverdek
• Victor Mulanovich
Acknowledgements
November 11, 2017
Samuel L. Aitken, PharmD, BCPS (AQ-ID)
Clinical Pharmacy Specialist, Infectious Diseases
Antimicrobial stewardship in managing septic patients