Evaluation of cefepime/enmetazobactam gradient strip and disk diffusion test for CTX-M-producing Enterobacterales

The global spread of extended-spectrum β-lactamase (ESBL)-producing enterobacterales represents a major clinical challenge often requiring carbapenem use with the consequent risk of selecting carbapenemase-producing strains. Recently, new β-lactam plus β-lactamase inhibitor formulations available could provide effective carbapenem-sparing alternatives. Among these, cefepime/enmetazobactam is tailored for extended-spectrum β-lactamase infection treatment. Here, we tested cefepime/enmetazobactam against a multicentre collection of 112 CTX-M-producing Escherichia coli and Klebsiella pneumoniae isolates from Northern Italy to evaluate the performance of gradient strip and disk diffusion testing compared with broth microdilution, and to assess the in vitro antimicrobial activity of this new formulation. Molecular testing for bla genes and CTX-M typing were also performed. The results showed 100% categorical agreement and no major error or very major error. All strains were susceptible to cefepime/enmetazobactam, and resistance was observed only in carbapenemase-producing strains. CTX-M-1 was predominant and several strains carried blaTEM and blaSHV. These data demonstrate good in vitro activity of cefepime/enmetazobactam against CTX-M-producing E. coli and K. pneumoniae. Moreover, disk diffusion proved reliable and reproducible for routine testing; gradient strips underestimated MIC values, which could be critical for isolates near the breakpoint.