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
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