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

Background: Carbapenem antibiotics are considered the treatment of choice for serious extended-spectrum betalactamase (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-beta-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 (%Delta = 14.0 [ 95% confidence interval: -2.4 to 31.1]), the microbiological eradication rate (%Delta = 4.1 [-5.0 to 13.4]), and the superimposed infection rate (%Delta = -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.