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Biochemical Insights into Imipenem Collateral Susceptibility Driven by ampC Mutations Conferring Ceftolozane/Tazobactam Resistance in Pseudomonas aeruginosa.

Gabriel CabotKi-Hun KimBrian L MarkAntonio OliverMazdak Khajehpour
Published in: Antimicrobial agents and chemotherapy (2023)
Several Pseudomonas aeruginosa AmpC mutants have emerged that exhibit enhanced activity against ceftazidime and ceftolozane, while also evading inhibition by avibactam. Interestingly, P. aeruginosa strains harboring these AmpC mutations fortuitously exhibit enhanced carbapenem susceptibility. This acquired susceptibility was investigated by comparing the degradation of imipenem by wild-type and cephalosporin-resistant AmpC. We show that cephalosporin-resistant AmpC enzymes lose their efficacy for hydrolyzing imipenem and suggest that this may be due to their increased flexibility and dynamics relative to the wild type.
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