Moxifloxacin versus ethambutol in the first 2 months of treatment for pulmonary tuberculosis.

RATIONALE Moxifloxacin has promising preclinical activity against Mycobacterium tuberculosis, but has not been evaluated in multidrug treatment of tuberculosis in humans. OBJECTIVE To compare the impact of moxifloxacin versus ethambutol, both in combination with isoniazid, rifampin, and pyrazinamide, on sputum culture conversion at 2 mo as a measure of the potential sterilizing activity of alternate induction regimens. METHODS Adults with smear-positive pulmonary tuberculosis were randomized in a factorial design to receive moxifloxacin (400 mg) versus ethambutol given 5 d/wk versus 3 d/wk (after 2 wk of daily therapy). All doses were directly observed. MEASUREMENTS The primary endpoint was sputum culture status at 2 mo of treatment. RESULTS Of 336 patients enrolled, 277 (82%) were eligible for the efficacy analysis, 186 (67%) were male, 175 (63%) were enrolled at African sites, 206 (74%) had cavitation on chest radiograph, and 60 (22%) had HIV infection. Two-month cultures were negative in 71% of patients (99 of 139) treated with moxifloxacin versus 71% (98 of 138) treated with ethambutol (p = 0.97). Patients receiving moxifloxacin, however, more often had negative cultures after 4 wk of treatment. Patients treated with moxifloxacin more often reported nausea (22 vs. 9%, p = 0.002), but similar proportions completed study treatment (88 vs. 89%). Dosing frequency had little effect on 2-mo culture status or tolerability of therapy. CONCLUSIONS The addition of moxifloxacin to isoniazid, rifampin, and pyrazinamide did not affect 2-mo sputum culture status but did show increased activity at earlier time points.