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.
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Xu et al. (2012) studied this question.