Dorman, Susan E.Johnson, John L.Goldberg, Stefan.Muzanye, Grace.Padayatchi, Nesri.Bozeman, Lorna.Heilig, Charles M.Bernardo, John.Choudhri, Shurjeel.Grosset, Jacques H.Guy, Elizabeth.Guyadeen, Priya.Leus, Maria Corazon.Maltas, Gina.Menzies, Dick.Nuermberger, Eric L.Villarino, Margarita.Vernon, Andrew.Chaisson, Richard E.2013-07-222013-07-2220092009Dorman, S.E., et al. 2009. Substitution of Moxifloxacin for Isoniazid during intensive phase treatment of Pulmonary Tuberculosis. American Journal of Respiratory and Critical Care Medicine 180 (3) pp. 273-280.1073-449Xhttp://dx.doi.org/10.1164/rccm.200901-0078OChttp://hdl.handle.net/10413/9343Rationale: Moxifloxacin has potent activity against Mycobacterium tuberculosis in vitro and in a mouse model of antituberculosis (TB) chemotherapy, but data regarding its activity in humans are limited. Objectives: Our objective was to compare the antimicrobial activity and safety of moxifloxacin versus isoniazid during the first 8 weeks of combination therapy for pulmonary TB. Methods: Adults with sputum smear–positive pulmonary TB were randomly assigned to receive either moxifloxacin 400 mg plus isoniazid placebo, or isoniazid 300 mg plus moxifloxacin placebo, administered 5 days/week for 8 weeks, in addition to rifampin, pyrazinamide, and ethambutol. All doses were directly observed. Sputum was collected for culture every 2 weeks. The primary outcome was negative sputum culture at completion of 8 weeks of treatment. Measurements and Main Results: Of 433 participants enrolled, 328 were eligible for the primary efficacy analysis. Of these, 35 (11%) were HIV positive, 248 (76%) had cavitation on baseline chest radiograph, and 213 (65%) were enrolled at African sites. Negative cultures at Week 8 were observed in 90/164 (54.9%) participants in the isoniazid arm, and 99/164 (60.4%) in the moxifloxacin arm (P=0.37). In multivariate analysis, cavitation and enrollment at an African site were associated with lower likelihood of Week-8 culture negativity. The proportion of participants who discontinued assigned treatment was 31/214 (14.5%) for the moxifloxacin group versus 22/205 (10.7%) for the isoniazid group (RR, 1.35; 95% CI, 0.81, 2.25).Conclusions: Substitution of moxifloxacin for isoniazid resulted in a small but statistically nonsignificant increase in Week-8 culture negativity.enTuberculosis, Pulmonary--Drug therapy.Tuberculosis, Pulmonary--Treatment.Antitubercular agents.HIV infections--Complications.Mycobacterium infections.Mycobacterium tuberculosis.Peer reviewed journal article