Efficacy and safety of de-escalation therapy to ertapenem for treatment of infections caused by extended-spectrum-β-lactamase-producing Enterobacteriaceae: an open-label randomized controlled trial

Pinyo Rattanaumpawan, Peerawong Werarak, Anupop Jitmuang, Pattarachai Kiratisin, Visanu Thamlikitkul, Pinyo Rattanaumpawan, Peerawong Werarak, Anupop Jitmuang, Pattarachai Kiratisin, Visanu Thamlikitkul

Abstract

Background: Carbapenem antibiotics are considered the treatment of choice for serious extended-spectrum beta-lactamase (ESBL)-producing Gram-negative bacteria (GNB) infections. The study objectives were to evaluate efficacy and safety of de-escalation therapy to ertapenem for treatment of infections caused by extended-spectrum-β-lactamase-producing Enterobacteriaceae.

Methods: We conducted a randomized controlled trial of adult patients with documented ESBL-producing Enterobacteriaceae infections who had received any group 2 carbapenem for less than 96 h. In the intervention group, the previously-prescribed group 2 carbapenem was de-escalated to ertapenem. In the control group, the group 2 carbapenem was continued.

Results: During June 2011-December 2014, 32 patients were randomized to the de-escalation group and 34 to the control group. Most common sites of infection were urinary tract infection (42%). Characteristics of both groups were comparable. By using a 15% predefined margin, ertapenem was non-inferior to control group regarding the clinical cure rate (%Δ = 14.0 [95% confidence interval: -2.4 to 31.1]), the microbiological eradication rate (%Δ = 4.1 [-5.0 to 13.4]), and the superimposed infection rate (%Δ = -16.5 [-38.4 to 5.3]). Patients in the de-escalation group had a significantly lower 28-day mortality rate (9.4% vs. 29.4%; P = .05), a significantly shorter median length of stay (16.5 days [4.0-73.25] vs. 20.0 days [1.0-112.25]; P = .04), and a significantly lower defined daily dose of carbapenem use (12.9 ± 8.9 vs. 18.4 ± 12.6; P = .05).

Conclusions: Ertapenem could be safely used as de-escalation therapy for ESBL-producing Enterobacteriaceae infections, once the susceptibility profiles are known. Future studies are needed to investigate ertapenem efficacy against ESBL-producing Enterobacteriaceae pneumonia to determine its applicability in life-threatening conditions.

Trial registration: ClinicalTrials.gov identifier: NCT01297842 . Registered on 14 February 2011. First patient enrolled on 27 June 2011.

Keywords: Carbapenem; De-escalation; ESBL; Enterobacteriaceae; Ertapenem.

Figures

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Fig. 1
Study flow chart

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