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.
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.
Authors: Scott M Irwin; Veronica Gruppo; Elizabeth Brooks; Janet Gilliland; Michael Scherman; Matthew J Reichlen; Rachel Leistikow; Igor Kramnik; Eric L Nuermberger; Martin I Voskuil; Anne J Lenaerts Journal: Antimicrob Agents Chemother Date: 2014-05-05 Impact factor: 5.191
Authors: Thomas J Hwang; Svetlana Dotsenko; Azizkhon Jafarov; Karin Weyer; Dennis Falzon; Kaspars Lunte; Paul Nunn; Ernesto Jaramillo; Salmaan Keshavjee; Douglas F Wares Journal: BMJ Open Date: 2014-01-02 Impact factor: 2.692