Available online 18 August 2022, 106660

A large collection of OXA-48-like producing isolates were tested for their susceptibilities to relebactam and vaborbactam

Susceptibility rates of imipenem was at 75.7% whereas it was at 81.3% for imipenem/relebactam combination

95.1 % of total isolates were susceptible to meropenm/vaborbactam combination whereas it was at 63.9% for meropenem at standard dosage but increased to 94.% at high exposure of meropenem

Ceftazidime/avibactam remains the best therapeutic option with a susceptibility rate at 99.5%

Relebactam and vaborbactam are among the last β-lactamase inhibitors marketed. They were originally designed to inhibit the Ambler class A carbapenemase KPC.

Here, imipenem-relebactam and meropenem-vaborbactam susceptibilities were determined on a collection of 407 OXA-48-like-producing Enterobacterales. The clonality and resistomes of the isolates were determined by WGS. Comparison was performed with other relevant antibiotics such as carbapenems alone, ceftazidime-avibactam or ceftolozane-tazobactam.

Addition of relebactam and vaborbactam did not significantly modify the MIC50 and MIC90 obtained for imipenem and meropenem alone. At the opposite, addition of avibactam strongly restored the ceftazidime susceptibility. According to EUCAST breakpoints, MIC50/MIC90 were at 2/4 mg/L, 2/4 mg/L, 2/8 mg/L, 2/8 mg/L, 32/>32 mg/L, and 0.5/2 mg/L for imipenem, imipenem-relebactam, meropenem, meropenem-vaborbactam, ceftazidime, and ceftazidime-avibactam, respectively. No differences were observed depending on the species.

This study highlighted the lack of benefit in vitro for carbapenem-inhibitor combination compared to carbapenem alone on OXA-48-producing isolates as well as the difficulties to compared molecules since carbapenem-inhibitor combinations were not developed with the same dosage of carbapenem.

Carbapenemase

beta-lactamase

beta-lactamase inhibitor

DBO

ceftolozane-tazobactam

© 2022 Published by Elsevier Ltd.