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.

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.

• Authors: Pinyo Rattanaumpawan, Peerawong Werarak, Anupop Jitmuang, Pattarachai Kiratisin, Visanu Thamlikitkul
• Journal: BMC infectious diseases (BMC Infect Dis) Vol. 17 Issue 1 Pg. 183 (03 01 2017) ISSN: 1471-2334 [Electronic] England
• PMID: 28249572 (Publication Type: Journal Article, Randomized Controlled Trial)

Chemical References

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

Topics

• Adult
• Aged
• Anti-Bacterial Agents (therapeutic use)
• Carbapenems (therapeutic use)
• Enterobacteriaceae (genetics, pathogenicity)
• Enterobacteriaceae Infections (drug therapy, microbiology)
• Ertapenem
• Female
• Humans
• Male
• Middle Aged
• Treatment Outcome
• Urinary Tract Infections (drug therapy)
• beta-Lactamases (metabolism)
• beta-Lactams (administration & dosage, therapeutic use)