In vitro activity of cefepime/zidebactam against sulbactam/durlobactam-susceptible and -resistant Acinetobacter baumannii clinical isolates

Objectives: To evaluate the in vitro activity of cefepime in association with a β-lactamase inhibitor (enmetazobactam) or β-lactam enhancer (BLE), zidebactam, against carbapenem-resistant Acinetobacter baumannii (CRAB) strains susceptible or resistant to sulbactam/durlobactam. Material and methods: Twenty-one CRAB clinical isolates were characterized by WGS and AST to cefepime/enmetazobactam, cefepime/zidebactam and comparators was determined. Results: Resistome analysis revealed that all CRAB carried bla OXA-23 carbapenemase genes, while bla ADC-25 and bla OXA-66 β-lactamase genes were observed exclusively in sulbactam/durlobactam-resistant strains. Analysis of penicillin-binding protein genes demonstrated the presence of specific mutations within PBP3 (N392T) previously associated to the resistance to sulbactam/durlobactam. Phenotypic analysis revealed that cefepime/enmetazobactam did not exert antibacterial activity against CRAB, while cefepime/zidebactam displayed potent bactericidal activity against both sulbactam/durlobactam-susceptible and -resistant strains. Conclusions: These results demonstrate that cefepime/zidebactam exhibited potent in vitro antibacterial activity against CRAB producing OXA carbapenemase and support its clinical use against both sulbactam/durlobactam-susceptible or -resistant isolates.