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Antimicrob Agents Chemother. 2015 Jan;59(1):673-6. doi: 10.1128/AAC.04019-14. Epub 2014 Oct 20.

Verapamil increases the bactericidal activity of bedaquiline against Mycobacterium tuberculosis in a mouse model.

Author information

1
Center for Tuberculosis Research, Department of Medicine, Johns Hopkins University, Baltimore, Maryland, USA Howard Hughes Medical Institute, Chevy Chase, Maryland, USA.
2
Center for Tuberculosis Research, Department of Medicine, Johns Hopkins University, Baltimore, Maryland, USA.
3
Center for Tuberculosis Research, Department of Medicine, Johns Hopkins University, Baltimore, Maryland, USA Howard Hughes Medical Institute, Chevy Chase, Maryland, USA wbishai@jhmi.edu.

Abstract

Bedaquiline is a newly approved drug for the treatment of multidrug-resistant tuberculosis, but there are concerns about its safety in humans. We found that the coadministration of verapamil with subinhibitory doses of bedaquiline gave the same bactericidal effect in mice as did the full human bioequivalent bedaquiline dosing. Adding verapamil to bedaquiline monotherapy also protected against the development of resistant mutants in vivo. The adjunctive use of verapamil may permit use of lower doses of bedaquiline to be used and thereby reduce its dose-related toxicities in tuberculosis patients.

PMID:
25331694
PMCID:
PMC4291418
DOI:
10.1128/AAC.04019-14
[Indexed for MEDLINE]
Free PMC Article

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