pa-824 and Leprosy

As measured by a proportional bactericidal technique in the mouse footpad system, the bactericidal activity against Mycobacterium leprae of R207910 was equal to that of rifapentine, rifampin, or moxifloxacin and significantly greater than those of minocycline, PA-824, and linezolid. These data suggest that R207910 may play an important role in treatment of leprosy.

Topics: Acetamides; Animals; Anti-Infective Agents; Aza Compounds; Diarylquinolines; Female; Fluoroquinolones; Leprosy; Linezolid; Mice; Moxifloxacin; Mycobacterium leprae; Nitroimidazoles; Oxazolidinones; Quinolines

Leprosy responds very slowly to the current multidrug therapy, and hence there is a need for novel drugs with potent bactericidal activity. PA-824 is a 4-nitroimidazo-oxazine that is currently undergoing phase I clinical trials for the treatment of tuberculosis. The activity of PA-824 against Mycobacterium leprae was tested and compared with that of rifampin in axenic cultures, macrophages, and two different animal models. Our results conclusively demonstrate that PA-824 has no effect on the viability of M. leprae in all three models, consistent with the lack of the nitroimidazo-oxazine-specific nitroreductase, encoded by Rv3547 in the M. leprae genome, which is essential for activation of this molecule.

Topics: Animals; Culture Media; Disease Models, Animal; Drug Resistance, Bacterial; Leprosy; Macrophages, Peritoneal; Mice; Mice, Inbred BALB C; Mice, Nude; Microbial Sensitivity Tests; Mycobacterium leprae; Nitroimidazoles