Sigmoid E max Modelling to Define the Fixed Concentration of Enmetazobactam for MIC Testing in Combination with Cefepime

Use of carbapenem antibiotics to treat infections caused by Enterobacterales expressing increasingly aggressive extended-spectrum β-lactamases (ESBL) 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 checkerboard minimum inhibitory concentration (MIC) profiles were obtained for a challenge panel of cefepime-resistant ESBL-producing clinical isolates of Klebsiella pneumoniae. Sigmoid Emax modelling described cefepime MIC as a function of enmetazobactam concentration with no bias. A concentration of 8 μg/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 μg/ml of enmetazobactam for MIC testing.