Abstract
Rationale: Although observational studies suggest that clofaziminecontaining regimens are highly active against drug-resistant tuberculosis, the contribution of clofazimine for the treatment of this disease has never been systematically evaluated. Objectives: Our goal wasto directlycomparethe activity of a standard second-line drug regimen with or without the addition of clofaziminein a mousemodelof multidrug-resistant tuberculosis.Our comparative outcomes included time to culture conversion in the mouse lungs and the percentage of relapses after treatment cessation. Methods: Mice were aerosol-infected with an isoniazid-resistant (as a surrogate ofmultidrug-resistant) strain of Mycobacterium tuberculosis. Treatment, which was administered for 5 to 9 months, was initiated 2 weeks after infection and comprised the following second-line regimen: daily (5 d/wk) moxifloxacin, ethambutol, and pyrazinamide, supplemented with amikacin during the first 2 months. One-half of the mice also received daily clofazimine. The decline in lung bacterial load was assessed monthly using charcoal-containing agar to reduce clofazimine carryover. Relapse was assessed 6months after treatment cessation. Measurements and Main Results: After 2 months, the bacillary load in lungs was reduced from 9.74 log10 at baseline to 3.61 and 4.68 in mice treated with or without clofazimine, respectively (P , 0.001). Mice treated with clofazimine were culture-negative after 5 months, whereas all mice treatedwithout clofazimine remainedheavily culturepositive for the entire 9 months of the study. The relapse rate was 7% amongmice treated with clofazimine for 8 to 9 months. Conclusions: The clofazimine contribution was substantial in these experimental conditions.
Original language | English (US) |
---|---|
Pages (from-to) | 608-612 |
Number of pages | 5 |
Journal | American journal of respiratory and critical care medicine |
Volume | 188 |
Issue number | 5 |
DOIs | |
State | Published - Sep 1 2013 |
Keywords
- Clofazimine
- Inbred BALB/c mice
- Multidrug-resistant tuberculosis
- Tuberculosis
ASJC Scopus subject areas
- Pulmonary and Respiratory Medicine
- Critical Care and Intensive Care Medicine