Published ahead of print on April 30, 2009, doi:10.1164/rccm.200901-0078OC
© 2009 American Thoracic Society doi: 10.1164/rccm.200901-0078OC
Substitution of Moxifloxacin for Isoniazid during Intensive Phase Treatment of Pulmonary Tuberculosis1 Johns Hopkins University Center for TB Research, Baltimore, Maryland; 2 Department of Medicine, Division of Infectious Diseases, Case Western Reserve University and University Hospitals Case Medical Center, Cleveland, Ohio; 3 Centers for Disease Control and Prevention, Atlanta, Georgia; 4 Uganda-Case Western Reserve University Research Collaboration, Kampala, Uganda; 5 CAPRISA and Department of Community Health, University of KwaZulu Natal, KwaZulu Natal, South Africa; 6 Boston University School of Medicine, Boston, Massachusetts; 7 Bayer, Inc., West Haven, Connecticut; 8 Baylor College of Medicine, Houston, Texas; 9 Westat, Rockville, Maryland; 10 University of Medicine and Dentistry of New Jersey, Newark, New Jersey; and 11 McGill University, Montreal, Quebec, Canada Correspondence and requests for reprints should be addressed to Susan E. Dorman, M.D., Johns Hopkins University Center for Tuberculosis Research, 1550 Orleans Street, Room 1M-06 Baltimore, MD 21231. E-mail dsusan1{at}jhmi.edu Rationale: 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. Clinical trial registered with www.clinicaltrials.gov (NCT00144417).
Key Words: tuberculosis • antitubercular agents • mycobacterium infections
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