Sterilizing activity of R207910 (TMC207)-containing regimens in the murine model of tuberculosis.
BACKGROUND
The diarylquinoline R207910 (TMC207) has potent bactericidal activity in a murine model of tuberculosis (TB), but its sterilizing activity has not been determined.


OBJECTIVE
To evaluate the sterilizing activity of R207910-containing combinations in the murine model of TB.


METHODS
Swiss mice were intravenously inoculated with 6 log(10) of Mycobacterium tuberculosis strain H37Rv, treated with R207910-containing regimens, and followed for 3 months to determine relapse rates (modified Cornell model).


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.
Ibrahim
Murad
M
Laboratoire de Bactériologie-Hygiène, Université Pierre et Marie Curie, Université Paris 6, Paris, France.
Truffot-Pernot
Chantal
C
Andries
Koen
K
Jarlier
Vincent
V
Veziris
Nicolas
N
D000818:Animals; D000995:Antitubercular Agents / Q000494:pharmacology*; D064687:Diarylquinolines; D004195:Disease Models, Animal; D004359:Drug Therapy, Combination; D005260:Female; D006867:Hydrolases / Q000096:biosynthesis; D007538:Isoniazid / Q000494:pharmacology; D051379:Mice; D009169:Mycobacterium tuberculosis / Q000254:growth & development / Q000378:metabolism; D011718:Pyrazinamide / Q000494:pharmacology; D011804:Quinolines / Q000494:pharmacology*; D012293:Rifampin / Q000494:pharmacology; D014376:Tuberculosis / Q000188:drug therapy* / Q000382:microbiology / Q000473:pathology; D014397:Tuberculosis, Pulmonary / Q000188:drug therapy / Q000382:microbiology / Q000473:pathology; D014400:Tuberculosis, Splenic / Q000188:drug therapy / Q000382:microbiology / Q000473:pathology
D000995:Antitubercular Agents; D064687:Diarylquinolines; D011804:Quinolines; D011718:Pyrazinamide; C493870:bedaquiline; D006867:Hydrolases; C527647:HsaD protein, Mycobacterium tuberculosis; D007538:Isoniazid; D012293:Rifampin