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

TL;DR

This study shows that cefepime combined with zidebactam effectively fights drug-resistant Acinetobacter bacteria in lab tests.

Contribution

The novel finding is that cefepime/zidebactam shows potent activity against both sulbactam/durlobactam-susceptible and -resistant Acinetobacter baumannii.

Findings

Cefepime/zidebactam displayed potent bactericidal activity against CRAB strains.

Resistance to sulbactam/durlobactam was linked to specific PBP3 mutations and β-lactamase genes.

Cefepime/enmetazobactam lacked antibacterial activity against CRAB.

Abstract

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.

Twenty-one CRAB clinical isolates were characterized by WGS and AST to cefepime/enmetazobactam, cefepime/zidebactam and comparators was determined.

Resistome analysis revealed that all CRAB carried blaOXA-23 carbapenemase genes, while blaADC-25 and blaOXA-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.

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.

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