Interactions of OP0595, a novel triple-action diazabicyclooctane, with β-lactams against OP0595-resistant Enterobacteriaceae mutants

David Livermore*, Marina Warner, Shazad Mushtaq, Neil Woodford

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

26 Citations (Scopus)

Abstract

OP0595 is a novel diazabicyclooctane which, like avibactam, inhibits class A and C β-lactamases. In addition, unlike avibactam, it has antibacterial activity, with MICs of 0.5 to 4 μg/ml for most members of the family Enterobacteriaceae, owing to inhibition of PBP2; moreover, it acts synergistically with PBP3-active β-lactams independently of β-lactamase inhibition, via an "enhancer effect." Enterobacteriaceae mutants stably resistant to 16 μg/ml OP0595 were selected on agar at frequencies of approximately 10-7. Unsurprisingly, OP0595 continued to potentiate substrate β-lactams against mutants derived from Enterobacteriaceae with OP0595-inhibited class A and C β-lactamases. Weaker potentiation of partners, especially aztreonam, cefepime, and piperacillin-less so meropenem-remained frequent for OP0595-resistant Enterobacteriaceae mutants lacking β-lactamases or with OP0595-resistant metallo-β-lactamases (MBLs), indicating that the enhancer effect is substantially retained even when antibiotic activity is lost.

Original languageEnglish
Pages (from-to)554-560
Number of pages7
JournalAntimicrobial Agents and Chemotherapy
Volume60
Issue number1
DOIs
Publication statusPublished - 1 Jan 2016

Bibliographical note

Funding Information:
Meiji Seika Pharma provided funding to David Livermore.

Publisher Copyright:
Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Fingerprint

Dive into the research topics of 'Interactions of OP0595, a novel triple-action diazabicyclooctane, with β-lactams against OP0595-resistant Enterobacteriaceae mutants'. Together they form a unique fingerprint.

Cite this