Cefepime/Enmetazobactam as a Carbapenem‐Sparing Alternative: Activity Against Extended‐Spectrum β‐Lactamase‐Producing Enterobacteria With and Without Carbapenemases in Southern Spain

ABSTRACT This study aims to evaluate the activity of Cefepime/enmetazobactam (FEP/META) in a Regional Hospital in southern Spain, against a collection of ESBL‐producing Enterobacteriaceae with or without carbapenemases, comparing it with piperacillin/tazobactam (PIP/TAZ) and meropenem (MER). A total of 150 ESBL‐, KPC‐, and OXA‐48‐producing strains were selected, excluding those producing metallo‐β‐lactamases. Of these isolates, 117 (78%) were from urine cultures and 33 (22%) from rectal colonization surveillance cultures. Isolates were collected between January 1, 2022, and June 30, 2024. Overall, 23% of ESBL‐producers were resistant to PIP/TAZ. Similarly, 30% of OXA‐48 producers were resistant to PIP/TAZ. FEP/META was the most active agent (7.1% of resistance) against ESBL and OXA‐48 producers' strains. KPC‐producers were all resistant to PIP/TAZ and FEP/META, while 66.7% were resistant to MER. Considering the total group of β‐lactamase‐producing bacteria, 48.67% were resistant to PIP/TAZ, compared to 6.67% to MER and 4.67% to FEP/META ( p value < 0.0001). Pairwise comparisons showed significant differences between FEP/META and PIP/TAZ, as well as between PIP/TAZ and MER ( p < 0.0001). FEP/META represents a promising therapeutic option for the treatment of infections caused by Gram‐negative bacteria resistant to third‐generation cephalosporins. It could also be an alternative to OXA‐48 carbapenemase‐producing Enterobacteriaceae.