Inactivation of the Pseudomonas-Derived Cephalosporinase-3 (PDC-3) by Relebactam-Reference-Cited by-同舟云学术

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

Published:2018-05 Issue:5 Volume:62 Page:
ISSN:0066-4804
Container-title:Antimicrobial Agents and Chemotherapy
language:en
Short-container-title:Antimicrob Agents Chemother

Author:

Barnes Melissa D.¹²,Bethel Christopher R.¹,Alsop Jim³,Becka Scott A.¹,Rutter Joseph D.¹,Papp-Wallace Krisztina M.¹²⁴⁵,Bonomo Robert A.¹²⁶⁷⁴

Affiliation:

1. Research Service, Louis Stokes Cleveland Department of Veterans Affairs, Cleveland, Ohio, USA

2. Department of Medicine, Case Western Reserve University, Cleveland, Ohio, USA

3. University of Minnesota, Minneapolis, Minnesota, USA

4. Department of Biochemistry, Case Western Reserve University, Cleveland, Ohio, USA

5. Department of Proteomics, Case Western Reserve University, Cleveland, Ohio, USA

6. Department of Molecular Biology and Microbiology, Case Western Reserve University, Cleveland, Ohio, USA

7. Department of Pharmacology, Case Western Reserve University, Cleveland, Ohio, USA

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 .

Funder

Veterans Affairs Merit Grant

HHS | National Institutes of Health

Merck

Publisher

American Society for Microbiology

Subject

Infectious Diseases,Pharmacology (medical),Pharmacology

Link

https://journals.asm.org/doi/pdf/10.1128/AAC.02406-17

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