Multidrug Resistant Pulmonary Tuberculosis Treatment Regimens and Patient Outcomes: An Individual Patient Data Meta-analysis of 9,153 Patients

Shama D. Ahuja, David Ashkin, Monika Avendano, Rita Banerjee, Melissa Bauer, Jamie N. Bayona, Mercedes C. Becerra, Andrea Benedetti, Marcos Burgos, Rosella Centis, Eward D. Chan, Chen Yuan Chiang, Helen Cox, Lia D'Ambrosio, Kathy DeRiemer, Nguyen Huy Dung, Donald Enarson, Dennis Falzon, Katherine Flanagan, Jennifer FloodMaria L. Garcia-Garcia, Neel Gandhi, Reuben M. Granich, Maria G. Hollm-Delgado, Timothy H. Holtz, Michael D. Iseman, Leah G. Jarlsberg, Salmaan Keshavjee, Hye Ryoun Kim, Won Jung Koh, Joey Lancaster, Christophe Lange, Wiel C M de Lange, Vaira Leimane, Chi Chiu Leung, Jiehui Li, Dick Menzies, Giovanni B. Migliori, Sergey P. Mishustin, Carole D. Mitnick, Masa Narita, Philly O'Riordan, Madhukar Pai, Domingo Palmero, Seung kyu Park, Geoffrey Pasvol, Jose Peña, Carlos Pérez-Guzmán, Maria I D Quelapio, Alfredo Ponce-de-Leon, Vija Riekstina, Jerome Robert, Sarah Royce, H. Simon Schaaf, Kwonjune J. Seung, Lena Shah, Tae Sun Shim, Sonya S. Shin, Yuji Shiraishi, José Sifuentes-Osornio, Giovanni Sotgiu, Matthew J. Strand, Payam Tabarsi, Thelma E. Tupasi, Robert van Altena, Martie van der Walt, Tjip S. van der Werf, Mario H. Vargas, Pirett Viiklepp, Janice Westenhouse, Wing Wai Yew, Jae Joon Yim

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368 Citations (Scopus)

Abstract

Background: Treatment of multidrug resistant tuberculosis (MDR-TB) is lengthy, toxic, expensive, and has generally poor outcomes. We undertook an individual patient data meta-analysis to assess the impact on outcomes of the type, number, and duration of drugs used to treat MDR-TB. Methods and Findings: Three recent systematic reviews were used to identify studies reporting treatment outcomes of microbiologically confirmed MDR-TB. Study authors were contacted to solicit individual patient data including clinical characteristics, treatment given, and outcomes. Random effects multivariable logistic meta-regression was used to estimate adjusted odds of treatment success. Adequate treatment and outcome data were provided for 9,153 patients with MDR-TB from 32 observational studies. Treatment success, compared to failure/relapse, was associated with use of: later generation quinolones, (adjusted odds ratio [aOR]: 2.5 [95% CI 1.1-6.0]), ofloxacin (aOR: 2.5 [1.6-3.9]), ethionamide or prothionamide (aOR: 1.7 [1.3-2.3]), use of four or more likely effective drugs in the initial intensive phase (aOR: 2.3 [1.3-3.9]), and three or more likely effective drugs in the continuation phase (aOR: 2.7 [1.7-4.1]). Similar results were seen for the association of treatment success compared to failure/relapse or death: later generation quinolones, (aOR: 2.7 [1.7-4.3]), ofloxacin (aOR: 2.3 [1.3-3.8]), ethionamide or prothionamide (aOR: 1.7 [1.4-2.1]), use of four or more likely effective drugs in the initial intensive phase (aOR: 2.7 [1.9-3.9]), and three or more likely effective drugs in the continuation phase (aOR: 4.5 [3.4-6.0]).Conclusions:In this individual patient data meta-analysis of observational data, improved MDR-TB treatment success and survival were associated with use of certain fluoroquinolones, ethionamide, or prothionamide, and greater total number of effective drugs. However, randomized trials are urgently needed to optimize MDR-TB treatment.Please see later in the article for the Editors' Summary.

Original languageEnglish
Article numbere1001300
JournalPLoS Medicine
Volume9
Issue number8
DOIs
Publication statusPublished - Aug 2012

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Multidrug-Resistant Tuberculosis
Metadata
Pulmonary Tuberculosis
Meta-Analysis
Prothionamide
Ethionamide
Odds Ratio
Pharmaceutical Preparations
Ofloxacin
Quinolones
Therapeutics
Poisons
Fluoroquinolones
Logistics
Recurrence
Observational Studies
Logistic Models

ASJC Scopus subject areas

  • Medicine(all)

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Multidrug Resistant Pulmonary Tuberculosis Treatment Regimens and Patient Outcomes : An Individual Patient Data Meta-analysis of 9,153 Patients. / Ahuja, Shama D.; Ashkin, David; Avendano, Monika; Banerjee, Rita; Bauer, Melissa; Bayona, Jamie N.; Becerra, Mercedes C.; Benedetti, Andrea; Burgos, Marcos; Centis, Rosella; Chan, Eward D.; Chiang, Chen Yuan; Cox, Helen; D'Ambrosio, Lia; DeRiemer, Kathy; Dung, Nguyen Huy; Enarson, Donald; Falzon, Dennis; Flanagan, Katherine; Flood, Jennifer; Garcia-Garcia, Maria L.; Gandhi, Neel; Granich, Reuben M.; Hollm-Delgado, Maria G.; Holtz, Timothy H.; Iseman, Michael D.; Jarlsberg, Leah G.; Keshavjee, Salmaan; Kim, Hye Ryoun; Koh, Won Jung; Lancaster, Joey; Lange, Christophe; de Lange, Wiel C M; Leimane, Vaira; Leung, Chi Chiu; Li, Jiehui; Menzies, Dick; Migliori, Giovanni B.; Mishustin, Sergey P.; Mitnick, Carole D.; Narita, Masa; O'Riordan, Philly; Pai, Madhukar; Palmero, Domingo; Park, Seung kyu; Pasvol, Geoffrey; Peña, Jose; Pérez-Guzmán, Carlos; Quelapio, Maria I D; Ponce-de-Leon, Alfredo; Riekstina, Vija; Robert, Jerome; Royce, Sarah; Schaaf, H. Simon; Seung, Kwonjune J.; Shah, Lena; Shim, Tae Sun; Shin, Sonya S.; Shiraishi, Yuji; Sifuentes-Osornio, José; Sotgiu, Giovanni; Strand, Matthew J.; Tabarsi, Payam; Tupasi, Thelma E.; van Altena, Robert; van der Walt, Martie; van der Werf, Tjip S.; Vargas, Mario H.; Viiklepp, Pirett; Westenhouse, Janice; Yew, Wing Wai; Yim, Jae Joon.

In: PLoS Medicine, Vol. 9, No. 8, e1001300, 08.2012.

Research output: Contribution to journalArticle

Ahuja, SD, Ashkin, D, Avendano, M, Banerjee, R, Bauer, M, Bayona, JN, Becerra, MC, Benedetti, A, Burgos, M, Centis, R, Chan, ED, Chiang, CY, Cox, H, D'Ambrosio, L, DeRiemer, K, Dung, NH, Enarson, D, Falzon, D, Flanagan, K, Flood, J, Garcia-Garcia, ML, Gandhi, N, Granich, RM, Hollm-Delgado, MG, Holtz, TH, Iseman, MD, Jarlsberg, LG, Keshavjee, S, Kim, HR, Koh, WJ, Lancaster, J, Lange, C, de Lange, WCM, Leimane, V, Leung, CC, Li, J, Menzies, D, Migliori, GB, Mishustin, SP, Mitnick, CD, Narita, M, O'Riordan, P, Pai, M, Palmero, D, Park, SK, Pasvol, G, Peña, J, Pérez-Guzmán, C, Quelapio, MID, Ponce-de-Leon, A, Riekstina, V, Robert, J, Royce, S, Schaaf, HS, Seung, KJ, Shah, L, Shim, TS, Shin, SS, Shiraishi, Y, Sifuentes-Osornio, J, Sotgiu, G, Strand, MJ, Tabarsi, P, Tupasi, TE, van Altena, R, van der Walt, M, van der Werf, TS, Vargas, MH, Viiklepp, P, Westenhouse, J, Yew, WW & Yim, JJ 2012, 'Multidrug Resistant Pulmonary Tuberculosis Treatment Regimens and Patient Outcomes: An Individual Patient Data Meta-analysis of 9,153 Patients', PLoS Medicine, vol. 9, no. 8, e1001300. https://doi.org/10.1371/journal.pmed.1001300
Ahuja, Shama D. ; Ashkin, David ; Avendano, Monika ; Banerjee, Rita ; Bauer, Melissa ; Bayona, Jamie N. ; Becerra, Mercedes C. ; Benedetti, Andrea ; Burgos, Marcos ; Centis, Rosella ; Chan, Eward D. ; Chiang, Chen Yuan ; Cox, Helen ; D'Ambrosio, Lia ; DeRiemer, Kathy ; Dung, Nguyen Huy ; Enarson, Donald ; Falzon, Dennis ; Flanagan, Katherine ; Flood, Jennifer ; Garcia-Garcia, Maria L. ; Gandhi, Neel ; Granich, Reuben M. ; Hollm-Delgado, Maria G. ; Holtz, Timothy H. ; Iseman, Michael D. ; Jarlsberg, Leah G. ; Keshavjee, Salmaan ; Kim, Hye Ryoun ; Koh, Won Jung ; Lancaster, Joey ; Lange, Christophe ; de Lange, Wiel C M ; Leimane, Vaira ; Leung, Chi Chiu ; Li, Jiehui ; Menzies, Dick ; Migliori, Giovanni B. ; Mishustin, Sergey P. ; Mitnick, Carole D. ; Narita, Masa ; O'Riordan, Philly ; Pai, Madhukar ; Palmero, Domingo ; Park, Seung kyu ; Pasvol, Geoffrey ; Peña, Jose ; Pérez-Guzmán, Carlos ; Quelapio, Maria I D ; Ponce-de-Leon, Alfredo ; Riekstina, Vija ; Robert, Jerome ; Royce, Sarah ; Schaaf, H. Simon ; Seung, Kwonjune J. ; Shah, Lena ; Shim, Tae Sun ; Shin, Sonya S. ; Shiraishi, Yuji ; Sifuentes-Osornio, José ; Sotgiu, Giovanni ; Strand, Matthew J. ; Tabarsi, Payam ; Tupasi, Thelma E. ; van Altena, Robert ; van der Walt, Martie ; van der Werf, Tjip S. ; Vargas, Mario H. ; Viiklepp, Pirett ; Westenhouse, Janice ; Yew, Wing Wai ; Yim, Jae Joon. / Multidrug Resistant Pulmonary Tuberculosis Treatment Regimens and Patient Outcomes : An Individual Patient Data Meta-analysis of 9,153 Patients. In: PLoS Medicine. 2012 ; Vol. 9, No. 8.
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title = "Multidrug Resistant Pulmonary Tuberculosis Treatment Regimens and Patient Outcomes: An Individual Patient Data Meta-analysis of 9,153 Patients",
abstract = "Background: Treatment of multidrug resistant tuberculosis (MDR-TB) is lengthy, toxic, expensive, and has generally poor outcomes. We undertook an individual patient data meta-analysis to assess the impact on outcomes of the type, number, and duration of drugs used to treat MDR-TB. Methods and Findings: Three recent systematic reviews were used to identify studies reporting treatment outcomes of microbiologically confirmed MDR-TB. Study authors were contacted to solicit individual patient data including clinical characteristics, treatment given, and outcomes. Random effects multivariable logistic meta-regression was used to estimate adjusted odds of treatment success. Adequate treatment and outcome data were provided for 9,153 patients with MDR-TB from 32 observational studies. Treatment success, compared to failure/relapse, was associated with use of: later generation quinolones, (adjusted odds ratio [aOR]: 2.5 [95{\%} CI 1.1-6.0]), ofloxacin (aOR: 2.5 [1.6-3.9]), ethionamide or prothionamide (aOR: 1.7 [1.3-2.3]), use of four or more likely effective drugs in the initial intensive phase (aOR: 2.3 [1.3-3.9]), and three or more likely effective drugs in the continuation phase (aOR: 2.7 [1.7-4.1]). Similar results were seen for the association of treatment success compared to failure/relapse or death: later generation quinolones, (aOR: 2.7 [1.7-4.3]), ofloxacin (aOR: 2.3 [1.3-3.8]), ethionamide or prothionamide (aOR: 1.7 [1.4-2.1]), use of four or more likely effective drugs in the initial intensive phase (aOR: 2.7 [1.9-3.9]), and three or more likely effective drugs in the continuation phase (aOR: 4.5 [3.4-6.0]).Conclusions:In this individual patient data meta-analysis of observational data, improved MDR-TB treatment success and survival were associated with use of certain fluoroquinolones, ethionamide, or prothionamide, and greater total number of effective drugs. However, randomized trials are urgently needed to optimize MDR-TB treatment.Please see later in the article for the Editors' Summary.",
author = "Ahuja, {Shama D.} and David Ashkin and Monika Avendano and Rita Banerjee and Melissa Bauer and Bayona, {Jamie N.} and Becerra, {Mercedes C.} and Andrea Benedetti and Marcos Burgos and Rosella Centis and Chan, {Eward D.} and Chiang, {Chen Yuan} and Helen Cox and Lia D'Ambrosio and Kathy DeRiemer and Dung, {Nguyen Huy} and Donald Enarson and Dennis Falzon and Katherine Flanagan and Jennifer Flood and Garcia-Garcia, {Maria L.} and Neel Gandhi and Granich, {Reuben M.} and Hollm-Delgado, {Maria G.} and Holtz, {Timothy H.} and Iseman, {Michael D.} and Jarlsberg, {Leah G.} and Salmaan Keshavjee and Kim, {Hye Ryoun} and Koh, {Won Jung} and Joey Lancaster and Christophe Lange and {de Lange}, {Wiel C M} and Vaira Leimane and Leung, {Chi Chiu} and Jiehui Li and Dick Menzies and Migliori, {Giovanni B.} and Mishustin, {Sergey P.} and Mitnick, {Carole D.} and Masa Narita and Philly O'Riordan and Madhukar Pai and Domingo Palmero and Park, {Seung kyu} and Geoffrey Pasvol and Jose Pe{\~n}a and Carlos P{\'e}rez-Guzm{\'a}n and Quelapio, {Maria I D} and Alfredo Ponce-de-Leon and Vija Riekstina and Jerome Robert and Sarah Royce and Schaaf, {H. Simon} and Seung, {Kwonjune J.} and Lena Shah and Shim, {Tae Sun} and Shin, {Sonya S.} and Yuji Shiraishi and Jos{\'e} Sifuentes-Osornio and Giovanni Sotgiu and Strand, {Matthew J.} and Payam Tabarsi and Tupasi, {Thelma E.} and {van Altena}, Robert and {van der Walt}, Martie and {van der Werf}, {Tjip S.} and Vargas, {Mario H.} and Pirett Viiklepp and Janice Westenhouse and Yew, {Wing Wai} and Yim, {Jae Joon}",
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month = "8",
doi = "10.1371/journal.pmed.1001300",
language = "English",
volume = "9",
journal = "Nature Methods",
issn = "1548-7091",
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TY - JOUR

T1 - Multidrug Resistant Pulmonary Tuberculosis Treatment Regimens and Patient Outcomes

T2 - An Individual Patient Data Meta-analysis of 9,153 Patients

AU - Ahuja, Shama D.

AU - Ashkin, David

AU - Avendano, Monika

AU - Banerjee, Rita

AU - Bauer, Melissa

AU - Bayona, Jamie N.

AU - Becerra, Mercedes C.

AU - Benedetti, Andrea

AU - Burgos, Marcos

AU - Centis, Rosella

AU - Chan, Eward D.

AU - Chiang, Chen Yuan

AU - Cox, Helen

AU - D'Ambrosio, Lia

AU - DeRiemer, Kathy

AU - Dung, Nguyen Huy

AU - Enarson, Donald

AU - Falzon, Dennis

AU - Flanagan, Katherine

AU - Flood, Jennifer

AU - Garcia-Garcia, Maria L.

AU - Gandhi, Neel

AU - Granich, Reuben M.

AU - Hollm-Delgado, Maria G.

AU - Holtz, Timothy H.

AU - Iseman, Michael D.

AU - Jarlsberg, Leah G.

AU - Keshavjee, Salmaan

AU - Kim, Hye Ryoun

AU - Koh, Won Jung

AU - Lancaster, Joey

AU - Lange, Christophe

AU - de Lange, Wiel C M

AU - Leimane, Vaira

AU - Leung, Chi Chiu

AU - Li, Jiehui

AU - Menzies, Dick

AU - Migliori, Giovanni B.

AU - Mishustin, Sergey P.

AU - Mitnick, Carole D.

AU - Narita, Masa

AU - O'Riordan, Philly

AU - Pai, Madhukar

AU - Palmero, Domingo

AU - Park, Seung kyu

AU - Pasvol, Geoffrey

AU - Peña, Jose

AU - Pérez-Guzmán, Carlos

AU - Quelapio, Maria I D

AU - Ponce-de-Leon, Alfredo

AU - Riekstina, Vija

AU - Robert, Jerome

AU - Royce, Sarah

AU - Schaaf, H. Simon

AU - Seung, Kwonjune J.

AU - Shah, Lena

AU - Shim, Tae Sun

AU - Shin, Sonya S.

AU - Shiraishi, Yuji

AU - Sifuentes-Osornio, José

AU - Sotgiu, Giovanni

AU - Strand, Matthew J.

AU - Tabarsi, Payam

AU - Tupasi, Thelma E.

AU - van Altena, Robert

AU - van der Walt, Martie

AU - van der Werf, Tjip S.

AU - Vargas, Mario H.

AU - Viiklepp, Pirett

AU - Westenhouse, Janice

AU - Yew, Wing Wai

AU - Yim, Jae Joon

PY - 2012/8

Y1 - 2012/8

N2 - Background: Treatment of multidrug resistant tuberculosis (MDR-TB) is lengthy, toxic, expensive, and has generally poor outcomes. We undertook an individual patient data meta-analysis to assess the impact on outcomes of the type, number, and duration of drugs used to treat MDR-TB. Methods and Findings: Three recent systematic reviews were used to identify studies reporting treatment outcomes of microbiologically confirmed MDR-TB. Study authors were contacted to solicit individual patient data including clinical characteristics, treatment given, and outcomes. Random effects multivariable logistic meta-regression was used to estimate adjusted odds of treatment success. Adequate treatment and outcome data were provided for 9,153 patients with MDR-TB from 32 observational studies. Treatment success, compared to failure/relapse, was associated with use of: later generation quinolones, (adjusted odds ratio [aOR]: 2.5 [95% CI 1.1-6.0]), ofloxacin (aOR: 2.5 [1.6-3.9]), ethionamide or prothionamide (aOR: 1.7 [1.3-2.3]), use of four or more likely effective drugs in the initial intensive phase (aOR: 2.3 [1.3-3.9]), and three or more likely effective drugs in the continuation phase (aOR: 2.7 [1.7-4.1]). Similar results were seen for the association of treatment success compared to failure/relapse or death: later generation quinolones, (aOR: 2.7 [1.7-4.3]), ofloxacin (aOR: 2.3 [1.3-3.8]), ethionamide or prothionamide (aOR: 1.7 [1.4-2.1]), use of four or more likely effective drugs in the initial intensive phase (aOR: 2.7 [1.9-3.9]), and three or more likely effective drugs in the continuation phase (aOR: 4.5 [3.4-6.0]).Conclusions:In this individual patient data meta-analysis of observational data, improved MDR-TB treatment success and survival were associated with use of certain fluoroquinolones, ethionamide, or prothionamide, and greater total number of effective drugs. However, randomized trials are urgently needed to optimize MDR-TB treatment.Please see later in the article for the Editors' Summary.

AB - Background: Treatment of multidrug resistant tuberculosis (MDR-TB) is lengthy, toxic, expensive, and has generally poor outcomes. We undertook an individual patient data meta-analysis to assess the impact on outcomes of the type, number, and duration of drugs used to treat MDR-TB. Methods and Findings: Three recent systematic reviews were used to identify studies reporting treatment outcomes of microbiologically confirmed MDR-TB. Study authors were contacted to solicit individual patient data including clinical characteristics, treatment given, and outcomes. Random effects multivariable logistic meta-regression was used to estimate adjusted odds of treatment success. Adequate treatment and outcome data were provided for 9,153 patients with MDR-TB from 32 observational studies. Treatment success, compared to failure/relapse, was associated with use of: later generation quinolones, (adjusted odds ratio [aOR]: 2.5 [95% CI 1.1-6.0]), ofloxacin (aOR: 2.5 [1.6-3.9]), ethionamide or prothionamide (aOR: 1.7 [1.3-2.3]), use of four or more likely effective drugs in the initial intensive phase (aOR: 2.3 [1.3-3.9]), and three or more likely effective drugs in the continuation phase (aOR: 2.7 [1.7-4.1]). Similar results were seen for the association of treatment success compared to failure/relapse or death: later generation quinolones, (aOR: 2.7 [1.7-4.3]), ofloxacin (aOR: 2.3 [1.3-3.8]), ethionamide or prothionamide (aOR: 1.7 [1.4-2.1]), use of four or more likely effective drugs in the initial intensive phase (aOR: 2.7 [1.9-3.9]), and three or more likely effective drugs in the continuation phase (aOR: 4.5 [3.4-6.0]).Conclusions:In this individual patient data meta-analysis of observational data, improved MDR-TB treatment success and survival were associated with use of certain fluoroquinolones, ethionamide, or prothionamide, and greater total number of effective drugs. However, randomized trials are urgently needed to optimize MDR-TB treatment.Please see later in the article for the Editors' Summary.

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JF - Nature Methods

SN - 1548-7091

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