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

• DOI: 10.1128/aac.00926-21
• Publication Date: 2021-06-13T22:38:48Z
• Authors: Philipp Knechtle; Stuart Shapiro; Ian Morrissey; Cyntia De Piano; Adam Belley
• Keywords: Cefepime; Carbapenem

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