Rapid emergence of resistance to broad-spectrum direct antimicrobial activity of avibactam.

ABSTRACT: Avibactam (AVI) is a diazabicyclooctane (DBO) β-lactamase inhibitor used clinically in combination with ceftazidime. At concentrations higher than those typically achieved in vivo, it also has broad-spectrum direct antibacterial activity against Enterobacterales strains, including metallo-β-lactamase-producing isolates, mediated by inhibition of penicillin-binding protein 2 (PBP2). This activity has some mechanistic similarities to that of more potent novel DBOs (zidebactam and nacubactam) in late clinical development. We found that resistance to AVI emerged readily, with a mutation frequency of 2 × 10^-6 to 8 × 10^-5. Whole-genome sequencing of resistant isolates revealed a heterogeneous mutational target that permitted bacterial survival and replication

SUBMITTER: Nageli M 

PROVIDER: S-EPMC12323667 | biostudies-literature | 2025 Aug

REPOSITORIES: biostudies-literature