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 |
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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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