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Abstract

Infections attributable to carbapenem-resistant Gram-negative bacilli are increasing globally. New antimicrobial agents are urgently needed to treat patients with these infections.

To describe susceptibility to the novel carbapenem-β-lactamase inhibitor combination imipenem-relebactam and comparators of clinical isolates of non-Proteeae (NPE) and from intraabdominal infections (IAIs) and urinary tract infections (UTIs).

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.

For NPE, 98.4 % of isolates from IAIs (=10,465) and 98.5 % of UTI isolates (=7,446) were susceptible to imipenem-relebactam, as were 42.4 % of imipenem-nonsusceptible (=474), 98.6 % of carbapenemase (KPC)-positive (=138), and 93.9 % of multidrug-resistant (MDR) isolates (=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 , 94.4 % of IAI (=1,245) and 93.0 % of UTI isolates (=714) were susceptible to imipenem-relebactam, as were 74.4 % of imipenem-nonsusceptible (=469) and 79.8 % of MDR isolates (=595) from IAIs and UTIs combined. Among the 120 isolates of that remained nonsusceptible to imipenem upon addition of relebactam, 72 % carried MBLs. The distribution of NPE and carrying carbapenemases varied substantially across Europe, as did resistance to imipenem and imipenem-relebactam.

Continued surveillance of antimicrobial resistance and resistance mechanisms, including the study of imipenem-relebactam as it approaches regulatory approval, appears warranted.

Funding
This study was supported by the:
  • Not Applicable , Merck
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/content/journal/jmm/10.1099/jmm.0.001142
2020-01-24
2020-02-28
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