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

OBJECTIVES:This 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. METHODS:A 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. RESULTS:Overall, 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. CONCLUSION:Cefepime/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.