Third-generation cephalosporin resistance in clinical isolates of Enterobacterales collected between 2016–2018 from USA and Europe: genotypic analysis of β-lactamases and comparative in vitro activity of cefepime/enmetazobactam

•Phenotypic resistance to third-generation cephalosporins (3GCs) seen in 17.5% of 7168 Enterobacterales clinical isolates.•Within the 3GC-resistant subgroup, 60.1% (n = 752) of isolates encoded an extended-spectrum β-lactamase (ESBL).•Susceptibility of 3GC-resistant subgroup to piperacillin/tazobactam and ceftolozane/tazobactam was <90%.•Projected susceptibility to investigational combination cefepime/enmetazobactam was 99.6%, comparable with meropenem (96%).•For 801 ESBL-producing isolates confirmed by genotyping, only meropenem & cefepime/enmetazobactam susceptibility was >90%.