Sterilizing activity of R207910 (TMC207)-containing regimens in the murine model of tuberculosisSterilizing activity of R207910 (TMC207)-containing regimens in the murine model of tuberculosis
Faculty of Pharmaceutical, Biomedical and Veterinary Sciences. Pharmacy
Laboratory for Microbiology, Parasitology and Hygiene (LMPH)
2009New York, 2009
American journal of respiratory and critical care medicine. - New York, 1994, currens
180(2009):6, p. 553-557
University of Antwerp
Rationale: The diarylquinoline R207910 (TMC207) has potent bactericidal activity in a murine model of tuberculosis (TB), but its sterilizing activity has not been determined. Objectives: To evaluate the sterilizing activity of R207910-containing combinations in the murine model of TB. Methods: Swiss mice were intravenously inoculated with 6 log10 of Mycobacterium tuberculosis strain H37Rv, treated with R207910-containing regimens, and followed for 3 months to determine relapse rates (modified Cornell model). Measurements and Main Results: Quantitative lung and spleen colony-forming unit counts and bacteriological relapse rates 3 months after the end of therapy were compared for the following regimens: 2, 3, or 4 months of R207910 (J) and pyrazinamide (Z) combined with rifampin (R) or isoniazid (H) or both and 3 or 4 months of a moxifloxacin (M)-containing regimen and 6 months of the standard WHO regimen RHZ. All J-treated mice were culture negative after 4 months of therapy. The relapse rate in the group treated with 4 months of JHRZ was similar to that of mice treated for 6 months with the RHZ regimen (6 vs. 17%; P = 0.54) and lower than that of RMZ (6 vs. 42%; P = 0,03), a moxifloxacin-containing regimen that was the most active in mice on once-daily basis. Conclusions: Four months of treatment with some J-containing regimens was as effective as the 6-month standard regimen and more effective than 4 months of treatment with M-containing regimens. Supplementation of standard regimen (RHZ) with J or substitution of J for H may shorten the treatment duration needed to cure TB in patients.