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

David Van Duin, Judith J. Lok, Michelle Earley, Eric Cober, Sandra S. Richter, Federico Perez, Robert A. Salata, Robert C. Kalayjian, Richard R. Watkins, Yohei Doi, Keith S. Kaye, Vance G. Fowler, David L. Paterson, Robert A. Bonomo, Scott Evans

Research output: Contribution to journalArticle

97 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)163-171
Number of pages9
JournalClinical Infectious Diseases
Volume66
Issue number2
DOIs
Publication statusPublished - 15-01-2018

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Colistin
Carbapenems
Enterobacteriaceae
Infection
Enterobacteriaceae Infections
Klebsiella pneumoniae
Therapeutics
Confidence Intervals
Klebsiella
Cephalosporins
Hospital Mortality
ceftazidime drug combination avibactam
Multicenter Studies
Observational Studies
Randomized Controlled Trials
Safety

All Science Journal Classification (ASJC) codes

  • Microbiology (medical)
  • Infectious Diseases

Cite this

Van Duin, D., Lok, J. J., Earley, M., Cober, E., Richter, S. S., Perez, F., ... Evans, S. (2018). Colistin Versus Ceftazidime-Avibactam in the Treatment of Infections Due to Carbapenem-Resistant Enterobacteriaceae. Clinical Infectious Diseases, 66(2), 163-171. https://doi.org/10.1093/cid/cix783
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. / Colistin Versus Ceftazidime-Avibactam in the Treatment of Infections Due to Carbapenem-Resistant Enterobacteriaceae. In: Clinical Infectious Diseases. 2018 ; Vol. 66, No. 2. pp. 163-171.
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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.",
author = "{Van Duin}, David and Lok, {Judith J.} and Michelle Earley and Eric Cober and Richter, {Sandra S.} and Federico Perez and Salata, {Robert A.} and Kalayjian, {Robert C.} and Watkins, {Richard R.} and Yohei Doi and Kaye, {Keith S.} and Fowler, {Vance G.} and Paterson, {David L.} and Bonomo, {Robert A.} and Scott Evans",
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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 2018, 'Colistin Versus Ceftazidime-Avibactam in the Treatment of Infections Due to Carbapenem-Resistant Enterobacteriaceae', Clinical Infectious Diseases, vol. 66, no. 2, pp. 163-171. https://doi.org/10.1093/cid/cix783

Colistin Versus 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.; Evans, Scott.

In: Clinical Infectious Diseases, Vol. 66, No. 2, 15.01.2018, p. 163-171.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Colistin Versus Ceftazidime-Avibactam in the Treatment of Infections Due to Carbapenem-Resistant Enterobacteriaceae

AU - Van Duin, David

AU - Lok, Judith J.

AU - Earley, Michelle

AU - Cober, Eric

AU - Richter, Sandra S.

AU - Perez, Federico

AU - Salata, Robert A.

AU - Kalayjian, Robert C.

AU - Watkins, Richard R.

AU - Doi, Yohei

AU - Kaye, Keith S.

AU - Fowler, Vance G.

AU - Paterson, David L.

AU - Bonomo, Robert A.

AU - Evans, Scott

PY - 2018/1/15

Y1 - 2018/1/15

N2 - 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.

AB - 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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