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

Publication ,  Journal Article
van Duin, D; Lok, JJ; Earley, M; Cober, E; Richter, SS; Perez, F; Salata, RA; Kalayjian, RC; Watkins, RR; Doi, Y; Kaye, KS; Fowler, VG ...
Published in: Clin Infect Dis
January 6, 2018

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.

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Published In

Clin Infect Dis

DOI

EISSN

1537-6591

Publication Date

January 6, 2018

Volume

66

Issue

2

Start / End Page

163 / 171

Location

United States

Related Subject Headings

  • beta-Lactamase Inhibitors
  • Treatment Outcome
  • Survival Analysis
  • Prospective Studies
  • Middle Aged
  • Microbiology
  • Male
  • Humans
  • Female
  • Enterobacteriaceae Infections
 

Citation

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van Duin, D., Lok, J. J., Earley, M., Cober, E., Richter, S. S., Perez, F., … Antibacterial Resistance Leadership Group. (2018). Colistin Versus Ceftazidime-Avibactam in the Treatment of Infections Due to Carbapenem-Resistant Enterobacteriaceae. Clin Infect Dis, 66(2), 163–171. https://doi.org/10.1093/cid/cix783
Duin, David van, Judith J. Lok, Michelle Earley, Eric Cober, Sandra S. Richter, Federico Perez, Robert A. Salata, et al. “Colistin Versus Ceftazidime-Avibactam in the Treatment of Infections Due to Carbapenem-Resistant Enterobacteriaceae.Clin Infect Dis 66, no. 2 (January 6, 2018): 163–71. https://doi.org/10.1093/cid/cix783.
van Duin D, Lok JJ, Earley M, Cober E, Richter SS, Perez F, et al. Colistin Versus Ceftazidime-Avibactam in the Treatment of Infections Due to Carbapenem-Resistant Enterobacteriaceae. Clin Infect Dis. 2018 Jan 6;66(2):163–71.
van Duin, David, et al. “Colistin Versus Ceftazidime-Avibactam in the Treatment of Infections Due to Carbapenem-Resistant Enterobacteriaceae.Clin Infect Dis, vol. 66, no. 2, Jan. 2018, pp. 163–71. Pubmed, doi:10.1093/cid/cix783.
van Duin D, Lok JJ, Earley M, Cober E, Richter SS, Perez F, Salata RA, Kalayjian RC, Watkins RR, Doi Y, Kaye KS, Fowler VG, Paterson DL, Bonomo RA, Evans S, Antibacterial Resistance Leadership Group. Colistin Versus Ceftazidime-Avibactam in the Treatment of Infections Due to Carbapenem-Resistant Enterobacteriaceae. Clin Infect Dis. 2018 Jan 6;66(2):163–171.
Journal cover image

Published In

Clin Infect Dis

DOI

EISSN

1537-6591

Publication Date

January 6, 2018

Volume

66

Issue

2

Start / End Page

163 / 171

Location

United States

Related Subject Headings

  • beta-Lactamase Inhibitors
  • Treatment Outcome
  • Survival Analysis
  • Prospective Studies
  • Middle Aged
  • Microbiology
  • Male
  • Humans
  • Female
  • Enterobacteriaceae Infections