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 | |
| State | Published - 1 Aug 2009 |
Keywords
- Antitubercular agents
- Mycobacterium infections
- Tuberculosis
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Substitution of moxifloxacin for isoniazid during intensive phase treatment of pulmonary tuberculosis. / Dorman, Susan E.; Johnson, John L.; Goldberg, Stefan; Muzanye, Grace; Padayatchi, Nesri; Bozeman, Lorna; Heilig, Charles M.; Bernardo, John; Choudhri, Shurjeel; Grosset, Jacques H.; Guy, Elizabeth; Guyadeen, Priya; Leus, Maria Corazon; Maltas, Gina; Menzies, Dick; Nuermberger, Eric L.; Villarino, Margarita; Vernon, Andrew; Chaisson, Richard E.; Mugerwa, Roy D.; Mayanja-Kizza, Harriet; Gitta, Phineas; Okwera, Alphonse; Lamunu, Dorcas; Nsubuga, Pheona; Joloba, Moses; Morgan, Karen; Mulumba, Yusuf; Nakibali, Joseph G.; Kimera, James; Ssaku, Elias; El-Sadr, Wafaa; Bamber, Sheila; Christop Chinappa, Surie T.; Hirsch-Moverman, Yael; Naidoo, Vikesh; Mnguni, Nelisiwe; Mthethwa, Thokozani; Gumede, Zevile; Ganas, Kaloshnee; Conde, Marcus B.; Efron, Anne; Loredo, Carla; Marsico, Anna Grazia; Vieira, Gisele Betzler De Oliveira; Weis, Stephen; King, Barbara; Turk, Le; Stevenson, Gloria; Helal, Joseph; Shafer, Norma; Dunbar, Denise; Hamill, Richard; Scott, Terry; Nickson, Ruby; Goodrich, Kathleen; Cayla, Joan A.; Miró, Jose M.; Sanchez, Francesca; Moreno, Antonio; Martinez, José A.; Sambeat, M. Antònia; López Colomés, Jose L.; De Souza, M. Luiza; Jiménez, M. Angeles; Milà, Celia; Lacasa, Xavier Martínez; Coll, Pere; Cuchi, Eva; Gonzalez, Julian; Martin, Nuria; Salvado, Margarita; Weiner, Marc H.; Wing, Richard; Wing, Diane; Uribe, Juan; Engle, Melissa; Calderin, Agustin; Catanzaro, Antonino; Moser, Kathleen S.; Tracy, Mark J.; Francisco, Vivien Peach; Davis, Judy; Reed, Sharon; Peter, Christopher R.; Jones, Brenda E.; Rayos, Ermelinda; Brown, Maria; Oamar, Bonnie P.; Sum, Samuel; Reves, Randall; Burman, William; Tapy, Jan; Belknap, Robert; Sanchez, Grace; Hildred, Ginger; Pachucki, Constance; Marantz, Susan; Lee, Anna; Samuel, Mary Poly; Kubba, Sue; Mangura, Bonita T.; Reichman, Lee B.; Owens, Marilyn; Napolitano, Eileen; Burday, Michelle; Sickles, Debra; Ray, Susan M.; Holland, David P.; Dixon, Deirdre; Mohamed, Omar; Folami, Kanoa; Bush, Jane; Duran, Paula; Sadkowski, Lee C.; Dorman, Susan; Fisher, James; Hooper, Nancy; Kepron, Wayne; Roth, Marian; Hoban, Daryl; Saukkonen, Jussi; Horsburgh, C. Robert; Murphy, Claire; Brett-Curran, Denise; Westerling, Judith; Schluger, Neil W.; Burzynski, Joseph; Lozano, Vilma; Wolk, Magda; Ebrahimzadeh, Adeleh; Hamilton, Carol Dukes; Stout, Jason; Mosher, Ann; Hecker, Emily; Bargothi, Shadia; Bhattacharya, Mondira; Lippold, Susan; Clapp, William; Fabre, Julie; Narwocki, John; Klein, Mary; Tankoano, Yombo; Badshah, Cyrus; Schichi, John; Al-Nasir, Mussa; Razeq, Jafar H.; Narita, Masa; Schwartz, Debra; Pass, Jean; Nahid, Payam; Hopewell, Philip; Merri-field, Cindy; Rudoy, Irina; Israel, Jill; Babst, Anna; Sterling, Timothy R.; Kerrigan, Amy; Smith, Teresa; Gordin, Fred M.; Benator, Debra; Conwell, Donna Sepulveda; Schwartzman, Kevin; Greenaway, Christina; Pelletier, Marthe; Valiquette, Chantal; Plaisir, Paul; Thibert, Louise.
In: American Journal of Respiratory and Critical Care Medicine, Vol. 180, No. 3, 01.08.2009, p. 273-280.Research output: Contribution to journal › Article › peer-review
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
VL - 180
SP - 273
EP - 280
JO - American Journal of Respiratory and Critical Care Medicine
JF - American Journal of Respiratory and Critical Care Medicine
SN - 1073-449X
IS - 3
ER -