Activity of MK-7655 combined with imipenem against Enterobacteriaceae and Pseudomonas aeruginosa

Livermore, David ORCID: https://orcid.org/0000-0002-9856-3703, Warner, Marina and Mushtaq, Shazad (2013) Activity of MK-7655 combined with imipenem against Enterobacteriaceae and Pseudomonas aeruginosa. Journal of Antimicrobial Chemotherapy, 68 (10). pp. 2286-2290. ISSN 0305-7453

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Abstract

Objectives MK-7655 is a novel inhibitor of class A and C ß-lactamases. We investigated its potential to protect imipenem. Methods Chequerboard MICs were determined by CLSI agar dilution: (i) for Enterobacteriaceae with carbapenemases; (ii) for Enterobacteriaceae with carbapenem resistance contingent on combinations of impermeability together with an extended-spectrum ß-lactamase or AmpC enzyme; and (iii) for Pseudomonas aeruginosa and other non-fermenters. Results At a concentration of 4 mg/L, MK-7655 reduced imipenem MICs for Enterobacteriaceae with KPC carbapenemases from 16–64 mg/L to 0.12–1 mg/L. Synergy also was seen for Enterobacteriaceae with impermeability-mediated carbapenem resistance, with weaker synergy seen for isolates with the OXA-48 enzyme. On the other hand, MK-7655 failed to potentiate imipenem against Enterobacteriaceae with metallo-carbapenemases. In the case of P. aeruginosa, where endogenous AmpC confers slight protection versus imipenem, 4 mg/L MK-7655 reduced the MIC of imipenem for all isolates, except those with metallo-carbapenemases: the MICs of imipenem fell from 1–2 mg/L to 0.25–0.5 mg/L for imipenem-susceptible P. aeruginosa and from 16–64 mg/L to 1–4 mg/L for OprD-deficient strains. No potentiation was seen for chryseobacteria or for Stenotrophomonas maltophilia. Conclusions MK-7655 potentiated imipenem against Enterobacteriaceae with KPC carbapenemases or combinations of ß-lactamase and impermeability, but not those with metallo-carbapenemases. It augmented the activity of imipenem against P. aeruginosa in general and OprD mutants in particular.

Item Type:	Article
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:	25 Sep 2013 01:03
Last Modified:	24 Oct 2022 04:40
URI:	https://ueaeprints.uea.ac.uk/id/eprint/43469
DOI:	10.1093/jac/dkt178

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