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

Livermore, David M. ORCID: https://orcid.org/0000-0002-9856-3703, Warner, Marina, Mushtaq, Shazad and Woodford, Neil (2016) Interactions of OP0595, a novel triple-action diazabicyclooctane, with β-lactams against OP0595-resistant Enterobacteriaceae mutants. Antimicrobial Agents and Chemotherapy, 60 (1). pp. 554-560. ISSN 0066-4804

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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 0.5-4 μg/ml for most Enterobacteriaceae, owing to inhibition of PBP2; moreover it synergizes 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 approx. 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, indicating that the enhancer effect is substantially retained even when antibiotic activity is lost.

Item Type:	Article
Uncontrolled Keywords:	avibactam,synergy,carbapenemase,esbl,ampc enzyme,pbp2
Faculty \ School:	Faculty of Medicine and Health Sciences > Norwich Medical School
UEA Research Groups:	Faculty of Medicine and Health Sciences > Research Groups > Epidemiology and Public Health Faculty of Medicine and Health Sciences > Research Groups > Public Health and Health Services Research (former - to 2023)
Depositing User:	Pure Connector
Date Deposited:	05 Jan 2016 14:00
Last Modified:	22 Oct 2022 00:24
URI:	https://ueaeprints.uea.ac.uk/id/eprint/56015
DOI:	10.1128/AAC.02184-15

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