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

Susan E. Dorman, John L. Johnson, Stefan Goldberg, Grace Muzanye, Nesri Padayatchi, Lorna Bozeman, Charles M. Heilig, John Bernardo, Shurjeel Choudhri, Jacques H. Grosset, Elizabeth Guy, Priya Guyadeen, Maria Corazon Leus, Gina Maltas, Dick Menzies, Eric L. Nuermberger, Margarita Villarino, Andrew Vernon, Richard E. Chaisson, Roy D. MugerwaHarriet Mayanja-Kizza, Phineas Gitta, Alphonse Okwera, Dorcas Lamunu, Pheona Nsubuga, Moses Joloba, Karen Morgan, Yusuf Mulumba, Joseph G. Nakibali, James Kimera, Elias Ssaku, Wafaa El-Sadr, Sheila Bamber, Surie T. Christop Chinappa, Yael Hirsch-Moverman, Vikesh Naidoo, Nelisiwe Mnguni, Thokozani Mthethwa, Zevile Gumede, Kaloshnee Ganas, Marcus B. Conde, Anne Efron, Carla Loredo, Anna Grazia Marsico, Gisele Betzler De Oliveira Vieira, Stephen Weis, Barbara King, Le Turk, Gloria Stevenson, Joseph Helal, Norma Shafer, Denise Dunbar, Richard Hamill, Terry Scott, Ruby Nickson, Kathleen Goodrich, Joan A. Cayla, Jose M. Miró, Francesca Sanchez, Antonio Moreno, José A. Martinez, M. Antònia Sambeat, Jose L. López Colomés, M. Luiza De Souza, M. Angeles Jiménez, Celia Milà, Xavier Martínez Lacasa, Pere Coll, Eva Cuchi, Julian Gonzalez, Nuria Martin, Margarita Salvado, Marc H. Weiner, Richard Wing, Diane Wing, Juan Uribe, Melissa Engle, Agustin Calderin, Antonino Catanzaro, Kathleen S. Moser, Mark J. Tracy, Vivien Peach Francisco, Judy Davis, Sharon Reed, Christopher R. Peter, Brenda E. Jones, Ermelinda Rayos, Maria Brown, Bonnie P. Oamar, Samuel Sum, Randall Reves, William Burman, Jan Tapy, Robert Belknap, Grace Sanchez, Ginger Hildred, Constance Pachucki, Susan Marantz, Anna Lee, Mary Poly Samuel, Sue Kubba, Bonita T. Mangura, Lee B. Reichman, Marilyn Owens, Eileen Napolitano, Michelle Burday, Debra Sickles, Susan M. Ray, David P. Holland, Deirdre Dixon, Omar Mohamed, Kanoa Folami, Jane Bush, Paula Duran, Lee C. Sadkowski, Susan Dorman, James Fisher, Nancy Hooper, Wayne Kepron, Marian Roth, Daryl Hoban, Jussi Saukkonen, C. Robert Horsburgh, Claire Murphy, Denise Brett-Curran, Judith Westerling, Neil W. Schluger, Joseph Burzynski, Vilma Lozano, Magda Wolk, Adeleh Ebrahimzadeh, Carol Dukes Hamilton, Jason Stout, Ann Mosher, Emily Hecker, Shadia Bargothi, Mondira Bhattacharya, Susan Lippold, William Clapp, Julie Fabre, John Narwocki, Mary Klein, Yombo Tankoano, Cyrus Badshah, John Schichi, Mussa Al-Nasir, Jafar H. Razeq, Masa Narita, Debra Schwartz, Jean Pass, Payam Nahid, Philip Hopewell, Cindy Merri-field, Irina Rudoy, Jill Israel, Anna Babst, Timothy R. Sterling, Amy Kerrigan, Teresa Smith, Fred M. Gordin, Debra Benator, Donna Sepulveda Conwell, Kevin Schwartzman, Christina Greenaway, Marthe Pelletier, Chantal Valiquette, Paul Plaisir, Louise Thibert

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215 Scopus citations

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).

Original languageEnglish
Pages (from-to)273-280
Number of pages8
JournalAmerican Journal of Respiratory and Critical Care Medicine
Volume180
Issue number3
DOIs
StatePublished - 1 Aug 2009

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Keywords

  • Antitubercular agents
  • Mycobacterium infections
  • Tuberculosis

Cite this

Dorman, S. E., Johnson, J. L., Goldberg, S., Muzanye, G., Padayatchi, N., Bozeman, L., Heilig, C. M., Bernardo, J., Choudhri, S., Grosset, J. H., Guy, E., Guyadeen, P., Leus, M. C., Maltas, G., Menzies, D., Nuermberger, E. L., Villarino, M., Vernon, A., Chaisson, R. E., ... Thibert, L. (2009). Substitution of moxifloxacin for isoniazid during intensive phase treatment of pulmonary tuberculosis. American Journal of Respiratory and Critical Care Medicine, 180(3), 273-280. https://doi.org/10.1164/rccm.200901-0078OC