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Am J Respir Crit Care Med. 2009 Aug 1;180(3):273-80. doi: 10.1164/rccm.200901-0078OC. Epub 2009 Apr 30.

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

Collaborators (182)

Johnson JL, Mugerwa RD, Mayanja-Kizza H, Muzanye G, Gitta P, Okwera A, Lamunu D, Nsubuga P, Joloba M, Morgan K, Mulumba Y, Nakibali JG, Kimera J, Ssaku E, El-Sadr W, Padayatchi N, Bamber S, Christop Chinappa ST, Hirsch-Moverman Y, Naidoo V, Mnguni N, Mthethwa T, Gumede Z, Ganas K, Conde MB, Efron A, Loredo C, Marsico AG, Vieira GB, Weis S, King B, Turk L, Stevenson G, Helal J, Shafer N, Dunbar D, Hamill R, Guy E, Scott T, Nickson R, Goodrich K, Cayla JA, Miró JM, Sanchez F, Moreno A, Martinez JA, Sambeat A, Colomés JL, de Souza L, Jiménez A, Milà C, Lacasa XM, Coll P, Cuchi E, Gonzalez J, Martin N, Salvado M, Weiner MH, Wing R, Wing D, Uribe J, Engle M, Calderin A, Catanzaro A, Moser KS, Tracy MJ, Francisco VP, Davis J, Reed S, Peter CR, Jones BE, Rayos E, Brown M, Oamar BP, Sum S, Reves R, Burman W, Tapy J, Belknap R, Sanchez G, Hildred G, Marantz S, Lee A, Samuel MP, Kubba S, Mangura BT, Reichman LB, Leus MC, Owens M, Napolitano E, Burday M, Sickles D, Ray SM, Holland DP, Dixon D, Mohamed O, Folami K, Bush J, Weiner MH, Engle M, Duran P, Sadkowski LC, Dorman S, Chaisson RE, Maltas G, Fisher J, Nancy Hooper NH, Kepron W, Roth M, Hoban D, Bernardo J, Saukkonen J, Horsburgh R Jr, Murphy C, Brett-Curran D, Westerling J, Schluger NW, Burzynski J, Lozano V, Wolk M, Ebrahimzadeh A, Hamilton CD, Stout J, Mosher A, Hecker E, Bargothi S, Bhattacharya M, Lippold S, Clapp W, Fabre J, Narwocki J, El-Sadr W, Klein M, Tankoano Y, Badshah C, Schichi J, Al-Nasir M, Razeq JH, Narita M, Schwartz D, Pass J, Nahid P, Hopewell P, Merrifield C, Rudoy I, Israel J, Babst A, Sterling TR, Kerrigan A, Smith T, Gordin FM, Benator D, Conwell DS, Hooper N, Menzies D, Schwartzman K, Greenaway C, Pelletier M, Valiquette C, Plaisir P, Thibert L, Borisov A, Sharma A, Bozeman L, Bliven E, Guyadeen P, Carter C, Fagley M, Gross L, Henderson C, Jackson M, Bozeman L, Diem L, Metchock B, Morlock G, Sikes D, Cowan L, Temporado D, Toney S, Neaton J, Kaplan J, Ashkin D.

Author information

1
Johns Hopkins University Center for Tuberculosis Research, Baltimore, Maryland 21231, USA. dsusan1@jhmi.edu

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.

TRIAL REGISTRATION:

ClinicalTrials.gov NCT00144417.

PMID:
19406981
DOI:
10.1164/rccm.200901-0078OC
[Indexed for MEDLINE]

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