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

• DOI: 10.1016/j.jgar.2021.02.031
• Publication Date: 2021-03-19T04:38:20Z
• Authors: Adam Belley; Ian Morrissey; Stephen Hawser; Nimmi Kothari; Philipp Knechtle
• Keywords: Cefepime; Tazobactam; Carbapenem

This study aimed to investigate third-generation cephalosporin (3GC) resistance determinants [extended-spectrum β-lactamases (ESBLs), AmpC and OXA-type β-lactamases] in contemporary clinical Enterobacterales isolates determine the vitro activity of β-lactams β-lactam/β-lactamase inhibitor combinations, including investigational combination cefepime novel β-lactamase enmetazobactam. Antibacterial susceptibility 7168 obtained between 2016–2018 from North America Europe was determined according CLSI guidelines. Phenotypic 3GC ceftazidime (MIC ≥ 16 µg/mL) and/or ceftriaxone 4 but retaining meropenem ≤ 1 determined. β-Lactamase genotyping performed on with ceftazidime, ceftriaxone, or MIC µg/mL. 3GCs occurred 17.5% tested isolates, whereas 2.1% were resistant carbapenem meropenem. Within 3GC-resistant subgroup, 60.1% (n = 752) encoded an ESBL, 25.6% 321) AmpC-type 0.9% 11) β-lactamase. Susceptibility subgroup piperacillin/tazobactam (57.5%) ceftolozane/tazobactam (71.3%) <90% based breakpoints established by CLSI. Projected cefepime/enmetazobactam 99.6% when applying susceptible, dose-dependent breakpoint 8 Against ESBL-producing 801) confirmed genotyping, only (96.0%) (99.9%) exceeded 90%. describes antibacterial important therapies against supports development as a carbapenem-sparing option for pathogens.