Title

Substitution of moxifloxacin for isoniazid during intensive phase treatment of pulmonary tuberculosis

Authors

Susan E. Dorman, Johns Hopkins University
John L. Johnson, University Hospitals Case Medical Center
Stefan Goldberg, Centers for Disease Control and Prevention
Grace Muzanye, Case Western Reserve University
Nesri Padayatchi, University of KwaZulu-Natal
Lorna Bozeman, Centers for Disease Control and Prevention
Charles M. Heilig, Centers for Disease Control and Prevention
John Bernardo, Boston University School of Medicine
Shurjeel Choudhri, Bayer Corporation, USA
Jacques H. Grosset, Johns Hopkins University
Elizabeth Guy, Baylor College of Medicine
Priya Guyadeen, Westat, Inc.
Maria Corazon Leus, Rutgers Biomedical and Health Sciences
Gina Maltas, Johns Hopkins University
Dick Menzies, Université McGill
Eric L. Nuermberger, Johns Hopkins University
Margarita Villarino, Centers for Disease Control and Prevention
Andrew Vernon, Centers for Disease Control and Prevention
Richard E. Chaisson, Johns Hopkins University
Roy D. Mugerwa, Case Western Reserve University
Harriet Mayanja-Kizza, Case Western Reserve University
Phineas Gitta, Case Western Reserve University
Alphonse Okwera, Case Western Reserve University
Dorcas Lamunu, Case Western Reserve University
Pheona Nsubuga, Case Western Reserve University
Moses Joloba, Case Western Reserve University
Karen Morgan, Case Western Reserve University
Yusuf Mulumba, Case Western Reserve University
Joseph G. Nakibali, Case Western Reserve University
James Kimera, Case Western Reserve University
Elias Ssaku, Case Western Reserve University
Wafaa El-Sadr, University of KwaZulu Natal-Harlem Hospital Research Collaboration

Document Type

Journal Article

Publication Date

8-1-2009

Journal

American Journal of Respiratory and Critical Care Medicine

Volume

180

Issue

3

DOI

10.1164/rccm.200901-0078OC

Keywords

Antitubercular agents; Mycobacterium infections; Tuberculosis

Abstract

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).

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