Evaluation of the activity of cefepime/enmetazobactam against Enterobacterales bacteria collected in Europe from 2019 to 2021, including third-generation cephalosporin-resistant isolates.

Abstract

ObjectivesThis study was performed to investigate the activity of the novel ß-lactam/ß-lactamase inhibitor combination cefepime/enmetazobactam, against recently circulating Enterobacterales isolates from Europe in 2019 to 2021. MethodsA total of 2,627 isolates were collected and antimicrobial susceptibility determined according to EUCAST guidelines. Isolates with phenotypic resistance to ceftriaxone and ceftazidime (but susceptible to meropenem), and isolates non-susceptible to meropenem were screened for the presence of ß-lactamases. ResultsOverall, susceptibility to third-generation cephalosporins was 77%, and 97.3% were susceptible to meropenem. Cefepime/enmetazobactam susceptibility was 97.9% (72% of these isolates were Klebsiella pneumoniae from Italy), compared to 80.0% susceptibility to piperacillin/tazobactam and 99.4% to ceftazidime/avibactam. A total of 320 isolates (12.2%) were resistant to third-generation cephalosporins but susceptible to meropenem and virtually all (96.3%) carried an ESBL with or without an AmpC and these were all susceptible to cefepime/enmetazobactam. Most meropenem-non-susceptible isolates carried a KPC (68%) which were not inhibited by cefepime/enmetazobactam but were inhibited by ceftazidime/avibactam. Most meropenem-non-susceptible isolates carrying OXA-48 (9/12 isolates) were susceptible to cefepime/enmetazobactam. ConclusionCefepime/enmetazobactam was highly active against Enterobacterales isolates, especially those resistant to third-generation cephalosporins. These data suggest that cefepime/enmetazobactam could be used as a carbapenem sparing agent to replace piperacillin/tazobactam.