In vitro antimicrobial activity of six novel β-lactam and β-lactamase inhibitor combinations and cefiderocol against NDM-producing Enterobacterales in China.

Abstract

Introduction: To date, the global prevalence of New Delhi metallo-β-lactamase (NDM) in carbapenem-resistant Enterobacterales (CRE) has been of concern, which is not inhibited by classical β-lactamase inhibitors (BLIs). In this study, we investigated the newly developed antimicrobial agents or inhibitors against NDM-producing Enterobacterales (NPEs).

Methods: The in vitro activities of cefiderocol, cefepime/taniborbactam, meropenem/taniborbactam, cefepime/zidebactam, meropenem/nacubactam, aztreonam/nacubactam and aztreonam/avibactam were analyzed in 204 NPE strains collected in China. The potential resistance mechanisms were identified by whole genome sequencing.

Results: Of 204 NPE strains, 18.1% (37/204) were resistant to cefiderocol, in which cirA deleterious alteration, PBP3 insertion and NDM production were taken as potential resistance mechanisms; 28.9% (59/204) were resistant to cefepime/zidebactam, involving K. pneumoniae with ompK35 deleterious alteration; 22.5% (46/204) were resistant to cefepime/taniborbactam, in which YRIN or YRIK inserted in PBP3 and altered ompC are more frequently detected in the resistant E. coli isolates; 27.9% (57/204) were resistant to meropenem/taniborbactam. Aztreonam/avibactam and aztreonam/nacubactam exhibited excellent activity against NPE. However, meropenem/nacubactam had the lowest activity, with only 49.0% (100/204) of all isolates having MICs of <4/4 mg/L.

Conclusions: Aztreonam/avibactam and aztreonam/nacubactam showed the highest activity against NPE. The potential resistance mechanisms of novel antimicrobial agents against NPE should be under active surveillance.