In vitro activity of imipenem-relebactam against clinical isolates of gram-negative bacilli isolated in hospital laboratories in the United States as part of the SMART 2016 program

Abstract

Relebactam is a non--lactam, bicyclic diazabicyclooctane -lactamase inhibitor of class A and class C -lactamases, including Klebsiella pneumoniae carbapenemases (KPCs). It is in phase 3 clinical development in combination with imipenem/cilastatin. The in vitro activities of imipenem-relebactam, imipenem, and comparators were determined using the Clinical and Laboratory Standards Institute (CLSI) reference broth microdilution method for isolates of Enterobacteriaceae (n 3,419) and Pseudomonas aeruginosa (n 896) collected in 2016 by 21 U.S. hospital laboratories participating in the SMART (Study for Monitoring Antimicrobial Resistance Trends) global surveillance program. Relebactam was tested at a fixed concentration of 4 g/ml. Imipenem-relebactam MICs were interpreted using CLSI breakpoints for imipenem. Rates of susceptibility to imipenem-relebactam and imipenem for non-Proteeae Enterobacteriaceae (n 3,143) and P. aeruginosa were 99.1% (3,115/3,143) and 95.9% (3,013/3,143) and were 94.4% (846/896) and 74.7% (669/ 896), respectively. Relebactam restored imipenem susceptibility to 78.5% (102/130) of imipenem-nonsusceptible non-Proteeae Enterobacteriaceae and to 78.0% (177/227) of imipenem-nonsusceptible P. aeruginosa isolates. Susceptibility to imipenem-relebactam was 98.2% (444/452) and 82.2% (217/264) for multidrug-resistant (MDR) non-Proteeae Enterobacteriaceae and MDR P. aeruginosa, respectively. Given the ability of relebactam to restore susceptibility to imipenem in nonsusceptible isolates of both non-Proteeae Enterobacteriaceae and P. aeruginosa and to demonstrate potent activity against current MDR isolates of both non-Proteeae Enterobacteriaceae and P. aeruginosa, further development of imipenem-relebactam appears warranted.