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Clin Infect Dis. 2018 Jan 6;66(2):163-171. doi: 10.1093/cid/cix783.

Colistin Versus Ceftazidime-Avibactam in the Treatment of Infections Due to Carbapenem-Resistant Enterobacteriaceae.

Author information

1
Division of Infectious Diseases, University of North Carolina, Chapel Hill.
2
Department of Biostatistics and the Center for Biostatistics in AIDS Research, Harvard T. H. Chan School of Public Health, Boston, Massachusetts.
3
Department of Infectious Diseases, Cleveland Clinic, Cleveland, Ohio.
4
Department of Laboratory Medicine, Cleveland Clinic, Cleveland, Ohio.
5
Research Service, Louis Stokes Cleveland Department of Veterans Affairs Medical Center, Cleveland, Ohio.
6
Division of Infectious Diseases and HIV Medicine, Department of Medicine, Case Western Reserve University School of Medicine, Cleveland, Ohio.
7
Department of Medicine, MetroHealth Medical Center, Cleveland, Ohio.
8
Department of Internal Medicine, Northeast Ohio Medical University, Rootstown, Ohio.
9
Division of Infectious Diseases, Cleveland Clinic Akron General, Ohio.
10
Division of Infectious Diseases, University of Pittsburgh School of Medicine, Pennsylvania.
11
Division of Infectious Diseases, University of Michigan, Ann Arbor.
12
Duke Clinical Research Institute, Duke University, Durham, North Carolina.
13
Division of Infectious Diseases, Duke University, Durham, North Carolina.
14
University of Queensland Centre for Clinical Research, Royal Brisbane and Women's Hospital Campus, Australia.
15
Department of Molecular Biology and Microbiology, Case Western Reserve University School of Medicine, Cleveland, Ohio.
16
Department of Pharmacology, Case Western Reserve University School of Medicine, Cleveland, Ohio.

Abstract

Background:

The efficacy of ceftazidime-avibactam-a cephalosporin-β-lactamase inhibitor combination with in vitro activity against Klebsiella pneumoniae carbapenemase-producing carbapenem-resistant Enterobacteriaceae (CRE)-compared with colistin remains unknown.

Methods:

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 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).

Results:

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 versus colistin, IPTW-adjusted all-cause hospital mortality 30 days after starting treatment was 9% versus 32%, respectively (difference, 23%; 95% bootstrap confidence interval, 9%-35%; P = .001). In an analysis of disposition at 30 days, patients treated with ceftazidime-avibactam, compared with those treated within colistin, had an IPTW-adjusted probability of a better outcome of 64% (95% confidence interval, 57%-71%). Partial credit analyses indicated uniform superiority of ceftazidime-avibactam to colistin.

Conclusions:

Ceftazidime-avibactam may be a reasonable alternative to colistin in the treatment of K. pneumoniae carbapenemase-producing CRE infections. These findings require confirmation in a randomized controlled trial.

KEYWORDS:

Klebsiella pneumoniae; benefit-risk; carbapenem-resistant Enterobacteriaceae; ceftazidime-avibactam; colistin

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