Ertapenem for the treatment of bloodstream infections due to ESBL-producing Enterobacteriaceae: a multinational pre-registered cohort study

J Antimicrob Chemother. 2016 Jun;71(6):1672-80. doi: 10.1093/jac/dkv502. Epub 2016 Feb 22.

Abstract

Objectives: Data about the efficacy of ertapenem for the treatment of bloodstream infections (BSI) due to ESBL-producing Enterobacteriaceae (ESBL-E) are limited. We compared the clinical efficacy of ertapenem and other carbapenems in monomicrobial BSI due to ESBL-E.

Methods: A multinational retrospective cohort study (INCREMENT project) was performed (ClinicalTrials.gov identifier: NCT01764490). Patients given monotherapy with ertapenem or other carbapenems were compared. Empirical and targeted therapies were analysed. Propensity scores were used to control for confounding; sensitivity analyses were performed in subgroups. The outcome variables were cure/improvement rate at day 14 and all-cause 30 day mortality.

Results: The empirical therapy cohort (ETC) and the targeted therapy cohort (TTC) included 195 and 509 patients, respectively. Cure/improvement rates were 90.6% with ertapenem and 75.5% with other carbapenems (P = 0.06) in the ETC and 89.8% and 82.6% (P = 0.02) in the TTC, respectively; 30 day mortality rates were 3.1% and 23.3% (P = 0.01) in the ETC and 9.3% and 17.1% (P = 0.01) in the TTC, respectively. Adjusted ORs (95% CI) for cure/improvement with empirical and targeted ertapenem were 1.87 (0.24-20.08; P = 0.58) and 1.04 (0.44-2.50; P = 0.92), respectively. For the propensity-matched cohorts it was 1.18 (0.43-3.29; P = 0.74). Regarding 30 day mortality, the adjusted HR (95% CI) for targeted ertapenem was 0.93 (0.43-2.03; P = 0.86) and for the propensity-matched cohorts it was 1.05 (0.46-2.44; P = 0.90). Sensitivity analyses were consistent except for patients with severe sepsis/septic shock, which showed a non-significant trend favouring other carbapenems.

Conclusions: Ertapenem appears as effective as other carbapenems for empirical and targeted therapy of BSI due to ESBL-E, but further studies are needed for patients with severe sepsis/septic shock.

Publication types

  • Clinical Trial
  • Comparative Study
  • Multicenter Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Aged
  • Anti-Bacterial Agents / therapeutic use*
  • Carbapenems / therapeutic use*
  • Enterobacteriaceae / enzymology*
  • Enterobacteriaceae / isolation & purification
  • Enterobacteriaceae Infections / drug therapy*
  • Enterobacteriaceae Infections / microbiology
  • Ertapenem
  • Female
  • Humans
  • Male
  • Middle Aged
  • Retrospective Studies
  • Sepsis / drug therapy*
  • Sepsis / microbiology
  • Survival Analysis
  • Treatment Outcome
  • beta-Lactamases / metabolism*
  • beta-Lactams / therapeutic use*

Substances

  • Anti-Bacterial Agents
  • Carbapenems
  • beta-Lactams
  • beta-Lactamases
  • Ertapenem

Associated data

  • ClinicalTrials.gov/NCT01764490