• Susan E Dorman, Stefan Goldberg, Jason E Stout, Grace Muzanyi, John L Johnson, Marc Weiner, Lorna Bozeman, Charles M Heilig, Pei-Jean Feng, Ruth Moro, Masahiro Narita, Payam Nahid, Susan Ray, Edward Bates, Betial Haile, Eric L Nuermberger, Andrew Vernon, Neil W Schluger, and Tuberculosis Trials Consortium.
• Johns Hopkins University School of Medicine, Baltimore, Maryland 21231, USA. dsusan1@jhmi.edu
• J. Infect. Dis. 2012 Oct 1;206(7):1030-40.

BackgroundRifapentine administered 5 days per week has potent activity in mouse models of antituberculosis chemotherapy, but efficacy and safety data are limited in humans. We compared the antimicrobial activity and safety of rifapentine vs rifampin during the first 8 weeks of pulmonary tuberculosis treatment.MethodsIn total, 531 adults with sputum smear-positive pulmonary tuberculosis were randomized to rifapentine 10 mg/kg/dose or rifampin 10 mg/kg/dose, administered 5 days per week for 8 weeks (intensive phase), with isoniazid, pyrazinamide, and ethambutol. Coprimary outcomes were negative sputum culture on liquid and on solid media at completion of intensive phase.ResultsNegative cultures on solid media occurred in 145 of 174 participants (83.3%) in the rifampin group and 171 of 198 participants (86.4%) in the rifapentine group (difference, 3.0%; 95% confidence interval [CI]: -4.3, 10.5); negative cultures in liquid media occurred in 110 of 169 (65.1%) in the rifampin group and 133 of 196 (67.9%) in the rifapentine group (difference, 2.8%; 95% CI: -6.9, 12.4). Among 529 participants who received study therapy, 40 of 254 participants (15.7%) in the rifampin group and 40 of 275 participants (14.5%) in the rifapentine group prematurely discontinued treatment (P=.79).ConclusionsThe rifapentine regimen was safe but not significantly more active than a standard rifampin regimen, by the surrogate endpoint of culture status at completion of intensive phase. Assessment of higher exposures to rifapentine for tuberculosis treatment is warranted.Clinical Trials RegistrationNCT00694629.

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