title: Clofazimine shortens the duration of the first-line treatment regimen for experimental chemotherapy of tuberculosis.
abstract: A key drug for the treatment of leprosy, clofazimine has recently been associated with highly effective and significantly shortened regimens for the treatment of multidrug-resistant tuberculosis (TB). Consequently, we hypothesized that clofazimine may also shorten the duration of treatment for drug-susceptible TB. We conducted a controlled trial in the mouse model of TB chemotherapy comparing the activity of the 6-mo standard regimen for TB treatment, i.e., 2 mo of daily rifampin, isoniazid, pyrazinamide, and ethambutol followed by 4 mo of rifampin and isoniazid, with a 4-mo clofazimine-containing regimen: 2 mo of daily rifampin, isoniazid, pyrazinamide, and clofazimine followed by 2 mo of rifampin, isoniazid, and clofazimine. Treatment efficacy was assessed on the basis of Mycobacterium tuberculosis colony counts in the lungs and spleens during treatment and on the proportion of mice with culture-positive relapse 6 mo after treatment cessation. No additive effect of clofazimine was observed after the first week of treatment, but, by the second week of treatment, the colony counts were significantly lower in the clofazimine-treated mice than in the mice receiving the standard regimen. Lung culture conversion was obtained after 3 and 5 mo in mice treated with the clofazimine-containing and standard regimens, respectively, and relapse-free cure was obtained after 3 and 6 mo of treatment with the clofazimine-containing and standard regimens, respectively. Thus, clofazimine is a promising anti-TB drug with the potential to shorten the duration of TB chemotherapy by at least half (3 mo vs. 6 mo) in the mouse model of TB.
authors.affiliation: Center for Tuberculosis Research, Johns Hopkins University School of Medicine, Baltimore, MD 21231;
authors.forename: Sandeep
authors.initials: S
authors.lastname: Tyagi
authors.affiliation: Center for Tuberculosis Research, Johns Hopkins University School of Medicine, Baltimore, MD 21231; KwaZulu-Natal Research Institute for Tuberculosis and HIV, Nelson R. Mandela School of Medicine, University of KwaZulu-Natal, Durban 4001, South Africa; and.
authors.forename: Nicole C
authors.initials: NC
authors.lastname: Ammerman
authors.affiliation: Center for Tuberculosis Research, Johns Hopkins University School of Medicine, Baltimore, MD 21231;
authors.forename: Si-Yang
authors.initials: SY
authors.lastname: Li
authors.affiliation: KwaZulu-Natal Research Institute for Tuberculosis and HIV, Nelson R. Mandela School of Medicine, University of KwaZulu-Natal, Durban 4001, South Africa; and.
authors.forename: John
authors.initials: J
authors.lastname: Adamson
authors.affiliation: Center for Tuberculosis Research, Johns Hopkins University School of Medicine, Baltimore, MD 21231;
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Converse
authors.affiliation: KwaZulu-Natal Research Institute for Tuberculosis and HIV, Nelson R. Mandela School of Medicine, University of KwaZulu-Natal, Durban 4001, South Africa; and School of Laboratory Medicine and Medical Sciences, College of Health Sciences, Nelson R. Mandela School of Medicine, University of KwaZulu-Natal, Durban 4001, South Africa.
authors.forename: Rosemary V
authors.initials: RV
authors.lastname: Swanson
authors.affiliation: Center for Tuberculosis Research, Johns Hopkins University School of Medicine, Baltimore, MD 21231; KwaZulu-Natal Research Institute for Tuberculosis and HIV, Nelson R. Mandela School of Medicine, University of KwaZulu-Natal, Durban 4001, South Africa; and jgrosse4@jhmi.edu dalmeid3@jhmi.edu.
authors.forename: Deepak V
authors.initials: DV
authors.lastname: Almeida
authors.affiliation: Center for Tuberculosis Research, Johns Hopkins University School of Medicine, Baltimore, MD 21231; KwaZulu-Natal Research Institute for Tuberculosis and HIV, Nelson R. Mandela School of Medicine, University of KwaZulu-Natal, Durban 4001, South Africa; and jgrosse4@jhmi.edu dalmeid3@jhmi.edu.
authors.forename: Jacques H
authors.initials: JH
authors.lastname: Grosset
mesh_terms: D000818:Animals; D000995:Antitubercular Agents / Q000627:therapeutic use*; D002991:Clofazimine / Q000627:therapeutic use*; D004195:Disease Models, Animal; D005260:Female; D051379:Mice; D008807:Mice, Inbred BALB C; D014376:Tuberculosis / Q000188:drug therapy*
chemical_list: D000995:Antitubercular Agents; D002991:Clofazimine
keywords: clofazimine; experimental chemotherapy; mouse model; tuberculosis; tuberculosis treatment