Are New β-Lactam/β-Lactamase Inhibitor Combinations Promising Against Carbapenem-Resistant Isolates?

BACKGROUND/OBJECTIVES: Carbapenem-resistant (CRKP) infections present a significant clinical challenge due to limited therapeutic options and high transmission potential. This study aimed to identify the resistance genes associated with carbapenemase production in CRKP isolates and evaluate the in vitro activity of ceftazidime/avibactam (CZA) and meropenem/vaborbactam (MEV), among other β-lactam/β-lactamase inhibitor combinations.

METHODS

Between October 2021 and June 2022, a total of 504 CRKP isolates were grown from patient samples in intensive care units. When duplicate patient samples were removed, the remaining 89 isolates were included in the study. Bacterial identification and antimicrobial susceptibility testing were per-formed using MALDI-TOF, Phoenix M50, and disk diffusion methods, following EUCAST guidelines. PCR analyses identified carbapenemase genes such as OXA-48, NDM, and KPC.

RESULTS

The most prevalent carbapenemase gene was OXA-48 (79.8%), followed by NDM (21.4%) and KPC (17.9%). The susceptibility rate to CZA was 82.0%, significantly higher than MEV (10.1%). All isolates were resistant to piperacillin/tazobactam and ceftolozane/tazobactam. Among MEV-resistant isolates, most carried the OXA-48 gene, while NDM was common in CZA-resistant isolates.

CONCLUSIONS

CZA demonstrates high efficacy against OXA-48-producing CRKP, making it a viable treatment option in settings where OXA-48 predominates. The limited activity of MEV in this study underscores the need for molecular surveillance of resistance mechanisms to guide empirical therapy.