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Relebactam is a non-β-lactam, bicyclic diazabicyclooctane β-lactamase inhibitor of class A and class C β-lactamases, includingKlebsiella pneumoniae carbapenemases (KPCs). It is in phase 3 clinical development in combination with imipenem/cilastatin. Thein vitro activities of imipenem-relebactam, imipenem, and comparators were determined using the Clinical and Laboratory Standards Institute (CLSI) reference broth microdilution method for isolates ofEnterobacteriaceae (n = 3,419) andPseudomonas 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) andP. 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-nonsusceptibleP. aeruginosa isolates. Susceptibility to imipenem-relebactam was 98.2% (444/452) and 82.2% (217/264) for multidrug-resistant (MDR) non-Proteeae Enterobacteriaceae and MDRP. aeruginosa , respectively. Given the ability of relebactam to restore susceptibility to imipenem in nonsusceptible isolates of both non-Proteeae Enterobacteriaceae andP. aeruginosa and to demonstrate potent activity against current MDR isolates of both non-Proteeae Enterobacteriaceae andP. aeruginosa , further development of imipenem-relebactam appears warranted.

antimicrobial agents and chemotherapy

<i>In Vitro</i> 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

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