Format

Send to

Choose Destination
J Antimicrob Chemother. 2013 Oct;68(10):2286-90. doi: 10.1093/jac/dkt178. Epub 2013 May 21.

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

Author information

1
Norwich Medical School, University of East Anglia, Norwich NR4 7TJ, UK.

Abstract

OBJECTIVES:

MK-7655 is a novel inhibitor of class A and C β-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 β-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 β-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.

KEYWORDS:

KPC; OXA-48; OprD porin; carbapenemases; metallo-β-lactamases

PMID:
23696619
DOI:
10.1093/jac/dkt178
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Silverchair Information Systems
Loading ...
Support Center