Susceptibility of OXA-48-producing Enterobacterales to imipenem/relebactam, meropenem/vaborbactam and ceftazidime/avibactam

Relebactam and vaborbactam are among the newest ,B-lactamase inhibitors marketed. They were orig-inally designed to inhibit the Ambler class A carbapenemase KPC. In this study, susceptibility to imipenem/relebactam and meropenem/vaborbactam was determined against a collection of OXA-48-like-producing Enterobacterales ( n = 407). The clonality and resistomes of the isolates were deter-mined by whole-genome sequencing. Comparison was performed with other relevant antibiotics such as carbapenems alone, ceftazidime/avibactam and ceftolozane/tazobactam. Addition of relebactam and vaborbactam did not significantly modify the MIC50 and MIC90 values obtained for imipenem and meropenem alone. In contrast, addition of avibactam strongly restored ceftazidime susceptibility. Accord-ing to European Committee on Antimicrobial Susceptibility Testing (EUCAST) breakpoints, MIC50/MIC90 values were at 2/4, 2/4, 2/8, 2/8, 32/ > 32 and 0.5/2 mg/L for imipenem, imipenem/relebactam, meropenem, meropenem/vaborbactam, ceftazidime and ceftazidime/avibactam, respectively. No differ-ences were observed depending on the species. This study highlights the lack of benefit in vitro for car-bapenem/inhibitor combination compared with carbapenem alone against OXA-48-producing isolates as well as the difficulties in comparing molecules since carbapenem/inhibitor combinations were not devel-oped with the same dosage of carbapenem. (c) 2022 Elsevier Ltd and International Society of Antimicrobial Chemotherapy. All rights reserved.