In vitro antimicrobial activity of six novel β-lactam and β-lactamase inhibitor combinations and cefiderocol against NDM-producing Enterobacterales in China
Xinmeng Liu, Ziyao Li, Feilong Zhang, Xinrui Yang, Zichen Lei, Li Chen, Yongli Wu, Jiankang Zhao, Yulin Zhang, Yanning Hu, FangFang Shen, Pingbang Wang, Junwen Yang, Yulei Liu, Huihui Shi, Binghuai Lu
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.