Inactivation of the Pseudomonas-Derived Cephalosporinase-3 (PDC-3) by Relebactam

2018/03/08 by Melissa D. Barnes, Christopher R. Bethel, Jim Alsop +6
Biochemistry, Genetics and Molecular Biology · Medicine · Environmental Science · #Antibiotic Resistance in Bacteria #Antibiotics Pharmacokinetics and Efficacy #Pharmaceutical and Antibiotic Environmental Impacts

paper · pdf · doi:10.1128/aac.02406-17

Abstract

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 k 2 / K of 41,400 M −1 s −1 and a k off 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 .

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