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Moxifloxacin versus Ethambutol in the First 2 Months of Treatment for Pulmonary Tuberculosis

Denver Public Health and the Department of Medicine, University of Colorado Health Sciences; National Jewish Medical and Research Center, Denver, Colorado; Division of Tuberculosis Elimination, Centers for Disease Control and Prevention, Atlanta, Georgia; Department of Medicine, Division of Infectious Diseases, Case Western Reserve University and University Hospitals of Cleveland, Cleveland, Ohio; Uganda–Case Western Reserve University Research Collaboration, Kampala, Uganda; South Texas Veterans Health Care System, San Antonio, Texas; Duke University Medical Center, Durham, North Carolina; Bayer, Inc., West Haven, Connecticut; New York City Department of Health and Mental Hygiene, New York, New York; and Johns Hopkins University Center for TB Research, Baltimore, Maryland

Correspondence and requests for reprints should be addressed to William J. Burman, M.D., 605 Bannock Street, Denver, CO 80204. E-mail: bburman{at}dhha.org

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.

Key Words: efficacy • moxifloxacin • randomized trial • toxicity • tuberculosis

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