Substitution of Moxifloxacin for Isoniazid during Intensive Phase Treatment of Pulmonary Tuberculosis


Por: Dorman, SE, Johnson, JL, Goldberg, S, Muzanye, G, Padayatchi, N, Bozeman, L, Heilig, CM, Bernardo, J, Choudhri, S, Grosset, JH, Guy, E, Guyadeen, P, Leus, MC, Maltas, G, Menzies, D, Nuermberger, EL, Villarino, M, Vernon, A, Chaisson, RE, Sanchez, F, Sambeat, MA, Coll P., TB Trials Consortium

Publicada: 1 ago 2009
Resumen:
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 ring 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.

Filiaciones:
Dorman, SE:
 Johns Hopkins Univ, Ctr TB Res, Baltimore, MD 21231 USA

Johnson, JL:
 Case Western Reserve Univ, Div Infect Dis, Dept Med, Cleveland, OH 44106 USA

 Univ Hosp Case Med Ctr, Cleveland, OH USA

Goldberg, S:
 Ctr Dis Control & Prevent, Atlanta, GA USA

Muzanye, G:
 Uganda Case Western Reserve Univ Res Collaborat, Kampala, Uganda

Padayatchi, N:
 Univ KwaZulu, CAPRISA, Kwa Zulu, South Africa

 Univ KwaZulu, Dept Community Hlth, Kwa Zulu, South Africa

Bozeman, L:
 Ctr Dis Control & Prevent, Atlanta, GA USA

Heilig, CM:
 Ctr Dis Control & Prevent, Atlanta, GA USA

Bernardo, J:
 Boston Univ, Sch Med, Boston, MA 02118 USA

Choudhri, S:
 Bayer Inc, West Haven, CT USA

Grosset, JH:
 Johns Hopkins Univ, Ctr TB Res, Baltimore, MD 21231 USA

Guy, E:
 Baylor Coll Med, Houston, TX 77030 USA

Guyadeen, P:
 WESTAT Corp, Rockville, MD 20850 USA

Leus, MC:
 Univ Med & Dent New Jersey, Newark, NJ 07103 USA

Maltas, G:
 Johns Hopkins Univ, Ctr TB Res, Baltimore, MD 21231 USA

Menzies, D:
 McGill Univ, Montreal, PQ, Canada

Nuermberger, EL:
 Johns Hopkins Univ, Ctr TB Res, Baltimore, MD 21231 USA

Villarino, M:
 Ctr Dis Control & Prevent, Atlanta, GA USA

Vernon, A:
 Ctr Dis Control & Prevent, Atlanta, GA USA

Chaisson, RE:
 Johns Hopkins Univ, Ctr TB Res, Baltimore, MD 21231 USA

Sanchez, F:
 Agència de Salut Pública de Barcelona, Barcelona, Spain

Sambeat, MA:
 Hospital de la Santa Creu i Sant Pau, Barcelona, Spain

 Universitat Autònoma de Barcelona, Cerdanyola del Valles, Spain

Coll P.:
 Hospital de la Santa Creu i Sant Pau, Barcelona, Spain
ISSN: 1073449X





AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
Editorial
AMER THORACIC SOC, 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA, Estados Unidos America
Tipo de documento: Article
Volumen: 180 Número: 3
Páginas: 273-280
WOS Id: 000268696000014
ID de PubMed: 19406981

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