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.

Automated summary

This study demonstrates that the addition of relebactam and vaborbactam did not significantly modify the susceptibility of OXA-48-like-producing Enterobacterales to imipenem and meropenem. However, the addition of avibactam strongly restored ceftazidime susceptibility.