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

Antimicrob Agents Chemother. 2018 Apr 26;62(5):e02406-17. doi: 10.1128/AAC.02406-17. Print 2018 May.

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.

Keywords: AmpC; PDC-3; Pseudomonas aeruginosa; diazabicyclooctane inhibitor; imipenem; relebactam; β-lactam; β-lactamase.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Azabicyclo Compounds / pharmacology
  • Cephalosporinase / metabolism*
  • Cilastatin / pharmacology
  • Imipenem / pharmacology
  • Microbial Sensitivity Tests
  • Pseudomonas / drug effects*
  • Pseudomonas aeruginosa / drug effects*
  • beta-Lactamase Inhibitors / pharmacology
  • beta-Lactamases / metabolism

Substances

  • Azabicyclo Compounds
  • beta-Lactamase Inhibitors
  • Cilastatin
  • Imipenem
  • Cephalosporinase
  • beta-Lactamases
  • relebactam