Sigmoid Emax Modeling To Define the Fixed Concentration of Enmetazobactam for MIC Testing in Combination with Cefepime

The use of carbapenem antibiotics to treat infections caused by Enterobacterales expressing increasingly aggressive extended-spectrum beta-lactamases (ESBLs) has contributed to the emergence of carbapenem resistance. Enmetazobactam is a novel ESBL inhibitor being developed in combination with cefepime as a carbapenem-sparing option for infections caused by ESBL-producing Enterobacterales. Cefepime-enmetazobactam checker-board MIC profiles were obtained for a challenge panel of cefepime-resistant ESBL-producing clinical isolates of Klebsiella pneumoniae. Sigmoid maximum effect (E-max) modeling described cefepime MICs as a function of enmetazobactam concentration with no bias. A concentration of 8 mu g/ml enmetazobactam proved sufficient to restore >95% of cefepime antibacterial activity in vitro against >95% of isolates tested. These results support a fixed concentration of 8 mu g/ml of enmetazobactam for MIC testing.