[Source: Antimicrobial Agents and Chemotherapy, full page: (LINK). Abstract, edited.]
In vitro activity of cefepime-enmetazobactam against Gram-negative isolates collected from United States and European hospitals during 2014-2015
Ian Morrissey, Sophie Magnet, Stephen Hawser, Stuart Shapiro, Philipp Knechtle
Enmetazobactam, formerly AAI101, is a novel penicillanic acid sulfone extended-spectrum β-lactamase inhibitor. The combination of enmetazobactam with cefepime has entered clinical trials to assess safety and efficacy in patients with complicated urinary tract infections. Here, the in vitro activity of cefepime-enmetazobactam was determined for 1,993 clinical isolates of Enterobacteriaceae and Pseudomonas aeruginosa collected in the US and Europe during 2014 and 2015. Enmetazobactam at a fixed concentration of 8 μg/ml lowered the cefepime MIC90from 16 to 0.12 μg/ml for Escherichia coli, >64 to 0.5 μg/ml for Klebsiella pneumoniae, 16 to 1 μg/ml for Enterobacter cloacae, and 0.5 to 0.25 μg/ml for Enterobacter aerogenes. Enmetazobactam did not enhance the potency of cefepime against P. aeruginosa. Applying the CLSI ‘susceptible-dose dependent’ (SDD) breakpoint of 8 μg/ml to cefepime-enmetazobactam for comparative purposes resulted in cumulative inhibitions of 99.9% for E. coli, 96.4% for K. pneumoniae, 97.0% for E. cloacae, 100% for E. aerogenes, 98.1% for all Enterobacteriaceae surveilled, and 82.8% for P. aeruginosa. Comparator susceptibilities for all Enterobacteriaceae were 99.7% for ceftazidime-avibactam, 96.2% for meropenem, 90.7% for ceftolozane-tazobactam, 87% for cefepime (SDD breakpoint), 85.7% for piperacillin-tazobactam, and 81.2% for ceftazidime. For the subset of ESBL-producing K. pneumoniae isolates, addition of 8 μg/ml enmetazobactam to cefepime lowered the MIC90 from >64 to 1 μg/ml, whereas the shift for 8 μg/ml tazobactam was from >64 to 8 μg/ml. Cefepime-enmetazobactam may represent a novel carbapenem-sparing option for empiric treatment of serious Gram-negative infections in settings where ESBL-producing Enterobacteriaceae are expected.
Copyright © 2019 Morrissey et al. This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license.
Keywords: Antibiotics; Drugs Resistance; Enterobacteriaceae; Cefepime; Enmetazobactam.