Colistin vs. Ceftazidime-avibactam in the Treatment of Infections due to Carbapenem-Resistant Enterobacteriaceae

van Duin, David, Lok, Judith J., Earley, Michelle, Cober, Eric, Richter, Sandra S., Perez, Federico, Salata, Robert A., Kalayjian, Robert C., Watkins, Richard R., Doi, Yohei, Kaye, Keith S., Fowler, Vance G., Paterson, David L., Bonomo, Robert A. and Evans, Scott (2017) Colistin vs. Ceftazidime-avibactam in the Treatment of Infections due to Carbapenem-Resistant Enterobacteriaceae. Clinical Infectious Diseases, 66 2: 163-171. doi:10.1093/cid/cix783

Author van Duin, David
Lok, Judith J.
Earley, Michelle
Cober, Eric
Richter, Sandra S.
Perez, Federico
Salata, Robert A.
Kalayjian, Robert C.
Watkins, Richard R.
Doi, Yohei
Kaye, Keith S.
Fowler, Vance G.
Paterson, David L.
Bonomo, Robert A.
Evans, Scott
Title Colistin vs. Ceftazidime-avibactam in the Treatment of Infections due to Carbapenem-Resistant Enterobacteriaceae
Journal name Clinical Infectious Diseases   Check publisher's open access policy
ISSN 1537-6591
Publication date 2017-09-04
Year available 2017
Sub-type Article (original research)
DOI 10.1093/cid/cix783
Open Access Status Not yet assessed
Volume 66
Issue 2
Start page 163
End page 171
Total pages 9
Place of publication Cary, NC United States
Publisher Oxford University Press
Language eng
Subject 2726 Microbiology (medical)
2725 Infectious Diseases
Abstract The efficacy of ceftazidime-avibactam - a cephalosporin-β-lactamase inhibitor combination with in vitro activity against Klebsiella pneumoniae carbapenemase (KPC)-producing carbapenem-resistant Enterobacteriaceae (CRE) - as compared to colistin remains unknown.

Patients initially treated with either ceftazidime-avibactam or colistin for CRE infections were selected from the Consortium on resistance against carbapenems in Klebsiella and other Enterobacteriaceae (CRACKLE), a prospective, multicenter, observational study. Efficacy, safety and benefit:risk analyses were performed using intent-to-treat analyses with partial credit and the desirability of outcome ranking (DOOR) approaches. The ordinal efficacy outcome was based on disposition at day 30 after starting treatment (home vs. not home but not observed to die in the hospital vs. hospital death). All analyses were adjusted for confounding using inverse probability of treatment weighting (IPTW).

Thirty-eight patients were treated first with ceftazidime-avibactam and 99 with colistin. Most patients received additional anti-CRE agents as part of their treatment. Bloodstream (n=63, 46%) and respiratory (n=30, 22%) infections were most common. In patients treated with ceftazidime-avibactam vs colistin, IPTW-adjusted all-cause hospital mortality at 30-days after starting treatment was 9% vs. 32%, respectively (Difference 23% [95% bootstrap CI: 9-35%], p=0.0012). When analyzing disposition at 30 days, patients treated with ceftazidime-avibactam had an IPTW-adjusted 64% (95% CI 57%-71%) probability of a better outcome as compared to patients treated with colistin. Partial credit analyses indicated uniform superiority of ceftazidime-avibactam to colistin.

Ceftazidime-avibactam may be a reasonable alternative to colistin in the treatment of KPC-producing CRE infections. These findings require confirmation in a randomized controlled trial.
Keyword Klebsiella pneumoniae
carbapenem-resistant Enterobacteriaceae
Q-Index Code C1
Q-Index Status Provisional Code
Grant ID R21 AI114508
UM1 AI104681
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: UQ Centre for Clinical Research Publications
HERDC Pre-Audit
Version Filter Type
Citation counts: Scopus Citation Count Cited 3 times in Scopus Article | Citations
Google Scholar Search Google Scholar
Created: Wed, 15 Nov 2017, 12:15:00 EST