Inactivation of the pseudomonas-derived cephalosporinase-3 (PDC-3) by Relebactam

Abstract

Pseudomonas aeruginosa is a prevalent and life-threatening Gram-negative pathogen. Pseudomonas-derived cephlosporinase (PDC) is the major inducible cephalosporinase in P. aeruginosa. In this investigation, we show that relebactam, a diazabicyclooctane β-lactamase inhibitor, potently inactivates PDC-3, with a k2/K of 41,400 M-1 s-1 and a koff of 0.00095 s-1. Relebactam restored susceptibility to imipenem in 62% of multidrug-resistant P. aeruginosa clinical isolates, while only 21% of isolates were susceptible to imipenem-cilastatin alone. Relebactam promises to increase the efficacy of imipenem-cilastatin against P. aeruginosa.