Preclinical Testing of the Nitroimidazopyran PA-824 for Activity against Mycobacterium tuberculosis in a Series of In Vitro and In Vivo Models

• DOI: 10.1128/aac.49.6.2294-2301.2005
• Publication Date: 2005-05-25T23:07:56Z
• Authors: Anne J. Lenaerts; Veronica Gruppo; Karen S. Marietta; Christine M. Johnson; Diane K. Driscoll; Nicholas M. Tompkins; Jerry D. Rose; Robert C. Reynolds; Ian M. Orme
• Keywords: Gatifloxacin

ABSTRACT This study extends earlier reports regarding the in vitro and vivo efficacies of nitroimidazopyran PA-824 against Mycobacterium tuberculosis . was tested a broad panel multidrug-resistant clinical isolates found to be highly active all (MIC < 1 μg/ml). The activity M. also assessed grown under conditions oxygen depletion. showed significant at 2, 10, 50 μg/ml, similar that metronidazole, dose-dependent manner. In short-course mouse infection model, efficacy 50, 100, 300 mg/kg body weight formulated methylcellulose or cyclodextrin/lecithin after nine oral treatments compared with those isoniazid, rifampin, moxifloxacin. 100 as moxifloxacin isoniazid 25 slightly more than rifampin 20 mg/kg. Long-term treatment reduced bacterial load below 500 CFU lungs spleen. No differences between other single drug (isoniazid mg/kg, 10 gatifloxacin mg/kg) could observed. summary, its good models, well potentially latent state, makes an attractive candidate for therapy tuberculosis. These data indicate there is potential effective delivery