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Int J Tuberc Lung Dis. 2012 Aug;16(8):1119-25. doi: 10.5588/ijtld.11.0752. Epub 2012 Jun 12.

In vitro and in vivo activity of clofazimine against Mycobacterium tuberculosis persisters.

Author information

1
Department of Pharmacology, Beijing Tuberculosis and Thoracic Tumour Research Institute, Beijing Chest Hospital, Capital Medical University, Beijing, China.

Abstract

OBJECTIVE:

To assess the activity of clofazimine (CFZ) against Mycobacterium tuberculosis persisters using an oxygen depletion model and a low-dose aerosol mouse model of chronic tuberculosis (TB).

DESIGN:

In in vitro experiments, CFZ showed much better activity than isoniazid under anaerobic conditions. In a low-dose aerosol mouse model of TB, we evaluated the efficacy of CFZ and moxifloxacin at different doses following treatment durations of 30, 60 and 90 days.

RESULTS:

CFZ showed significant bactericidal activity in the mouse model over the wide dose range of 2-200 mg/kg. CFZ activity was dose-dependent. The bacilli were eradicated in the CFZ 200 mg/kg group after treatment for 60 days, and in the CFZ 20 mg/kg group after 90 days of treatment.

CONCLUSION:

CFZ exhibits dose-dependent, sustained bactericidal activity against M. tuberculosis persisters, and thus warrants further study to demonstrate its potential to contribute significantly in a novel treatment-shortening regimen.

PMID:
22691726
DOI:
10.5588/ijtld.11.0752
[Indexed for MEDLINE]

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