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.

Relebactam is a non-β-lactam, bicyclic diazabicyclooctane β-lactamase inhibitor of class A and class C β-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 μg/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.