In vitro activity of imipenem-relebactam against resistant phenotypes of Enterobacteriaceae and Pseudomonas aeruginosa isolated from intraabdominal and urinary tract infection samples - SMART Surveillance Europe 2015-2017.

Introduction. Infections attributable to carbapenem-resistant Gram-negative bacilli are increasing globally. New antimicrobial agents are urgently needed to treat patients with these infections. Aim. To describe susceptibility to the novel carbapenem-β-lactamase inhibitor combination imipenem-relebactam and comparators of clinical isolates of non-Proteeae Enterobacteriaceae (NPE) and Pseudomonas aeruginosa from intraabdominal infections (IAIs) and urinary tract infections (UTIs). Methods. Broth microdilution MICs were determined for isolates collected in 22 European countries in 2015-2017 and interpreted using EUCAST breakpoints; imipenem-relebactam MICs were interpreted using imipenem breakpoints. Results. For NPE, 98.4 % of isolates from IAIs ( n =10,465) and 98.5 % of UTI isolates ( n =7,446) were susceptible to imipenem-relebactam, as were 42.4 % of imipenem-nonsusceptible ( n =474), 98.6 % of Klebsiella pneumoniae carbapenemase (KPC)-positive ( n =138), and 93.9 % of multidrug-resistant (MDR) isolates ( n =4,424) from IAIs and UTIs combined. Molecular analysis demonstrated that two-thirds of imipenem-nonsusceptible isolates rendered susceptible by relebactam carried KPCs; 96 % (261/271) of imipenem-nonsusceptible isolates of NPE that remained nonsusceptible in the presence of relebactam carried metallo-β-lactamase (MBL)-type and/or OXA-48-like carbapenemases. Among P. aeruginosa , 94.4 % of IAI ( n =1,245) and 93.0 % of UTI isolates ( n =714) were susceptible to imipenem-relebactam, as were 74.4 % of imipenem-nonsusceptible ( n =469) and 79.8 % of MDR isolates ( n =595) from IAIs and UTIs combined. Among the 120 isolates of P. aeruginosa that remained nonsusceptible to imipenem upon addition of relebactam, 72 % carried MBLs. The distribution of NPE and P. aeruginosa carrying carbapenemases varied substantially across Europe, as did resistance to imipenem and imipenem-relebactam. Conclusions. Continued surveillance of antimicrobial resistance and resistance mechanisms, including the study of imipenem-relebactam as it approaches regulatory approval, appears warranted.