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. Mugerwa; Harriet 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

doi:10.1164/rccm.200901-0078OC

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

Research output: Contribution to journal › Article › peer-review

236 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 language	English
Pages (from-to)	273-280
Number of pages	8
Journal	American Journal of Respiratory and Critical Care Medicine
Volume	180
Issue number	3
DOIs	https://doi.org/10.1164/rccm.200901-0078OC
State	Published - 1 Aug 2009

Keywords

Antitubercular agents
Mycobacterium infections
Tuberculosis

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10.1164/rccm.200901-0078OC

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

@article{94c48d76a0a1477287a87ea1c780bf2f,

title = "Substitution of moxifloxacin for isoniazid during intensive phase treatment of pulmonary 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).",

keywords = "Antitubercular agents, Mycobacterium infections, Tuberculosis",

author = "Dorman, {Susan E.} and Johnson, {John L.} and Stefan Goldberg and Grace Muzanye and Nesri Padayatchi and Lorna Bozeman and Heilig, {Charles M.} and John Bernardo and Shurjeel Choudhri and Grosset, {Jacques H.} and Elizabeth Guy and Priya Guyadeen and Leus, {Maria Corazon} and Gina Maltas and Dick Menzies and Nuermberger, {Eric L.} and Margarita Villarino and Andrew Vernon and Chaisson, {Richard E.} and Mugerwa, {Roy D.} and Harriet Mayanja-Kizza and Phineas Gitta and Alphonse Okwera and Dorcas Lamunu and Pheona Nsubuga and Moses Joloba and Karen Morgan and Yusuf Mulumba and Nakibali, {Joseph G.} and James Kimera and Elias Ssaku and Wafaa El-Sadr and Sheila Bamber and {Christop Chinappa}, {Surie T.} and Yael Hirsch-Moverman and Vikesh Naidoo and Nelisiwe Mnguni and Thokozani Mthethwa and Zevile Gumede and Kaloshnee Ganas and Conde, {Marcus B.} and Anne Efron and Carla Loredo and Marsico, {Anna Grazia} and Vieira, {Gisele Betzler De Oliveira} and Stephen Weis and Barbara King and Le Turk and Gloria Stevenson and Joseph Helal and Norma Shafer and Denise Dunbar and Richard Hamill and Terry Scott and Ruby Nickson and Kathleen Goodrich and Cayla, {Joan A.} and Mir{\'o}, {Jose M.} and Francesca Sanchez and Antonio Moreno and Martinez, {Jos{\'e} A.} and Sambeat, {M. Ant{\`o}nia} and {L{\'o}pez Colom{\'e}s}, {Jose L.} and {De Souza}, {M. Luiza} and Jim{\'e}nez, {M. Angeles} and Celia Mil{\`a} and Lacasa, {Xavier Mart{\'i}nez} and Pere Coll and Eva Cuchi and Julian Gonzalez and Nuria Martin and Margarita Salvado and Weiner, {Marc H.} and Richard Wing and Diane Wing and Juan Uribe and Melissa Engle and Agustin Calderin and Antonino Catanzaro and Moser, {Kathleen S.} and Tracy, {Mark J.} and Francisco, {Vivien Peach} and Judy Davis and Sharon Reed and Peter, {Christopher R.} and Jones, {Brenda E.} and Ermelinda Rayos and Maria Brown and Oamar, {Bonnie P.} and Samuel Sum and Randall Reves and William Burman and Jan Tapy and Robert Belknap and Grace Sanchez and Ginger Hildred and Constance Pachucki and Susan Marantz and Anna Lee and Samuel, {Mary Poly} and Sue Kubba and Mangura, {Bonita T.} and Reichman, {Lee B.} and Marilyn Owens and Eileen Napolitano and Michelle Burday and Debra Sickles and Ray, {Susan M.} and Holland, {David P.} and Deirdre Dixon and Omar Mohamed and Kanoa Folami and Jane Bush and Paula Duran and Sadkowski, {Lee C.} and Susan Dorman and James Fisher and Nancy Hooper and Wayne Kepron and Marian Roth and Daryl Hoban and Jussi Saukkonen and Horsburgh, {C. Robert} and Claire Murphy and Denise Brett-Curran and Judith Westerling and Schluger, {Neil W.} and Joseph Burzynski and Vilma Lozano and Magda Wolk and Adeleh Ebrahimzadeh and Hamilton, {Carol Dukes} and Jason Stout and Ann Mosher and Emily Hecker and Shadia Bargothi and Mondira Bhattacharya and Susan Lippold and William Clapp and Julie Fabre and John Narwocki and Mary Klein and Yombo Tankoano and Cyrus Badshah and John Schichi and Mussa Al-Nasir and Razeq, {Jafar H.} and Masa Narita and Debra Schwartz and Jean Pass and Payam Nahid and Philip Hopewell and Cindy Merri-field and Irina Rudoy and Jill Israel and Anna Babst and Sterling, {Timothy R.} and Amy Kerrigan and Teresa Smith and Gordin, {Fred M.} and Debra Benator and Conwell, {Donna Sepulveda} and Kevin Schwartzman and Christina Greenaway and Marthe Pelletier and Chantal Valiquette and Paul Plaisir and Louise Thibert",

year = "2009",

month = aug,

day = "1",

doi = "10.1164/rccm.200901-0078OC",

language = "English",

volume = "180",

pages = "273--280",

journal = "American Journal of Respiratory and Critical Care Medicine",

issn = "1073-449X",

publisher = "American Thoracic Society",

number = "3",

}

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, Mugerwa, RD, Mayanja-Kizza, H, Gitta, P, Okwera, A, Lamunu, D, Nsubuga, P, Joloba, M, Morgan, K, Mulumba, Y, Nakibali, JG, Kimera, J, Ssaku, E, El-Sadr, W, 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, GBDO, Weis, S, King, B, Turk, L, Stevenson, G, Helal, J, Shafer, N, Dunbar, D, Hamill, R, Scott, T, Nickson, R, Goodrich, K, Cayla, JA, Miró, JM, Sanchez, F, Moreno, A, Martinez, JA, Sambeat, MA, López Colomés, JL, De Souza, ML, Jiménez, MA, 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, Pachucki, C, Marantz, S, Lee, A, Samuel, MP, Kubba, S, Mangura, BT, Reichman, LB, Owens, M, Napolitano, E, Burday, M, Sickles, D, Ray, SM, Holland, DP, Dixon, D, Mohamed, O, Folami, K, Bush, J, Duran, P, Sadkowski, LC, Dorman, S, Fisher, J, Hooper, N, Kepron, W, Roth, M, Hoban, D, Saukkonen, J, Horsburgh, CR, 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, Klein, M, Tankoano, Y, Badshah, C, Schichi, J, Al-Nasir, M, Razeq, JH, Narita, M, Schwartz, D, Pass, J, Nahid, P, Hopewell, P, Merri-field, C, Rudoy, I, Israel, J, Babst, A, Sterling, TR, Kerrigan, A, Smith, T, Gordin, FM, Benator, D, Conwell, DS, Schwartzman, K, Greenaway, C, Pelletier, M, Valiquette, C, Plaisir, P & Thibert, L 2009, 'Substitution of moxifloxacin for isoniazid during intensive phase treatment of pulmonary tuberculosis', American Journal of Respiratory and Critical Care Medicine, vol. 180, no. 3, pp. 273-280. https://doi.org/10.1164/rccm.200901-0078OC

TY - JOUR

T1 - Substitution of moxifloxacin for isoniazid during intensive phase treatment of pulmonary tuberculosis

AU - Dorman, Susan E.

AU - Johnson, John L.

AU - Goldberg, Stefan

AU - Muzanye, Grace

AU - Padayatchi, Nesri

AU - Bozeman, Lorna

AU - Heilig, Charles M.

AU - Bernardo, John

AU - Choudhri, Shurjeel

AU - Grosset, Jacques H.

AU - Guy, Elizabeth

AU - Guyadeen, Priya

AU - Leus, Maria Corazon

AU - Maltas, Gina

AU - Menzies, Dick

AU - Nuermberger, Eric L.

AU - Villarino, Margarita

AU - Vernon, Andrew

AU - Chaisson, Richard E.

AU - Mugerwa, Roy D.

AU - Mayanja-Kizza, Harriet

AU - Gitta, Phineas

AU - Okwera, Alphonse

AU - Lamunu, Dorcas

AU - Nsubuga, Pheona

AU - Joloba, Moses

AU - Morgan, Karen

AU - Mulumba, Yusuf

AU - Nakibali, Joseph G.

AU - Kimera, James

AU - Ssaku, Elias

AU - El-Sadr, Wafaa

AU - Bamber, Sheila

AU - Christop Chinappa, Surie T.

AU - Hirsch-Moverman, Yael

AU - Naidoo, Vikesh

AU - Mnguni, Nelisiwe

AU - Mthethwa, Thokozani

AU - Gumede, Zevile

AU - Ganas, Kaloshnee

AU - Conde, Marcus B.

AU - Efron, Anne

AU - Loredo, Carla

AU - Marsico, Anna Grazia

AU - Vieira, Gisele Betzler De Oliveira

AU - Weis, Stephen

AU - King, Barbara

AU - Turk, Le

AU - Stevenson, Gloria

AU - Helal, Joseph

AU - Shafer, Norma

AU - Dunbar, Denise

AU - Hamill, Richard

AU - Scott, Terry

AU - Nickson, Ruby

AU - Goodrich, Kathleen

AU - Cayla, Joan A.

AU - Miró, Jose M.

AU - Sanchez, Francesca

AU - Moreno, Antonio

AU - Martinez, José A.

AU - Sambeat, M. Antònia

AU - López Colomés, Jose L.

AU - De Souza, M. Luiza

AU - Jiménez, M. Angeles

AU - Milà, Celia

AU - Lacasa, Xavier Martínez

AU - Coll, Pere

AU - Cuchi, Eva

AU - Gonzalez, Julian

AU - Martin, Nuria

AU - Salvado, Margarita

AU - Weiner, Marc H.

AU - Wing, Richard

AU - Wing, Diane

AU - Uribe, Juan

AU - Engle, Melissa

AU - Calderin, Agustin

AU - Catanzaro, Antonino

AU - Moser, Kathleen S.

AU - Tracy, Mark J.

AU - Francisco, Vivien Peach

AU - Davis, Judy

AU - Reed, Sharon

AU - Peter, Christopher R.

AU - Jones, Brenda E.

AU - Rayos, Ermelinda

AU - Brown, Maria

AU - Oamar, Bonnie P.

AU - Sum, Samuel

AU - Reves, Randall

AU - Burman, William

AU - Tapy, Jan

AU - Belknap, Robert

AU - Sanchez, Grace

AU - Hildred, Ginger

AU - Pachucki, Constance

AU - Marantz, Susan

AU - Lee, Anna

AU - Samuel, Mary Poly

AU - Kubba, Sue

AU - Mangura, Bonita T.

AU - Reichman, Lee B.

AU - Owens, Marilyn

AU - Napolitano, Eileen

AU - Burday, Michelle

AU - Sickles, Debra

AU - Ray, Susan M.

AU - Holland, David P.

AU - Dixon, Deirdre

AU - Mohamed, Omar

AU - Folami, Kanoa

AU - Bush, Jane

AU - Duran, Paula

AU - Sadkowski, Lee C.

AU - Dorman, Susan

AU - Fisher, James

AU - Hooper, Nancy

AU - Kepron, Wayne

AU - Roth, Marian

AU - Hoban, Daryl

AU - Saukkonen, Jussi

AU - Horsburgh, C. Robert

AU - Murphy, Claire

AU - Brett-Curran, Denise

AU - Westerling, Judith

AU - Schluger, Neil W.

AU - Burzynski, Joseph

AU - Lozano, Vilma

AU - Wolk, Magda

AU - Ebrahimzadeh, Adeleh

AU - Hamilton, Carol Dukes

AU - Stout, Jason

AU - Mosher, Ann

AU - Hecker, Emily

AU - Bargothi, Shadia

AU - Bhattacharya, Mondira

AU - Lippold, Susan

AU - Clapp, William

AU - Fabre, Julie

AU - Narwocki, John

AU - Klein, Mary

AU - Tankoano, Yombo

AU - Badshah, Cyrus

AU - Schichi, John

AU - Al-Nasir, Mussa

AU - Razeq, Jafar H.

AU - Narita, Masa

AU - Schwartz, Debra

AU - Pass, Jean

AU - Nahid, Payam

AU - Hopewell, Philip

AU - Merri-field, Cindy

AU - Rudoy, Irina

AU - Israel, Jill

AU - Babst, Anna

AU - Sterling, Timothy R.

AU - Kerrigan, Amy

AU - Smith, Teresa

AU - Gordin, Fred M.

AU - Benator, Debra

AU - Conwell, Donna Sepulveda

AU - Schwartzman, Kevin

AU - Greenaway, Christina

AU - Pelletier, Marthe

AU - Valiquette, Chantal

AU - Plaisir, Paul

AU - Thibert, Louise

PY - 2009/8/1

Y1 - 2009/8/1

N2 - 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).

AB - 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).

KW - Antitubercular agents

KW - Mycobacterium infections

KW - Tuberculosis

UR - http://www.scopus.com/inward/record.url?scp=67749086328&partnerID=8YFLogxK

U2 - 10.1164/rccm.200901-0078OC

DO - 10.1164/rccm.200901-0078OC

M3 - Article

C2 - 19406981

AN - SCOPUS:67749086328

SN - 1073-449X

VL - 180

SP - 273

EP - 280

JO - American Journal of Respiratory and Critical Care Medicine

JF - American Journal of Respiratory and Critical Care Medicine

IS - 3

ER -

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

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