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Research Article

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

  • Shama D. Ahuja,

    Affiliation: Bureau of Tuberculosis, New York, New York, United States of America

    X
  • David Ashkin,

    Affiliation: A.G. Holley Hospital, Lantana, Florida, United States of America

    X
  • Monika Avendano,

    Affiliation: University of Toronto, Toronto, Canada

    X
  • Rita Banerjee,

    Affiliation: Mayo Clinic, Rochester, Minnesota, United States of America

    X
  • Melissa Bauer,

    Affiliation: Montreal Chest Institute, McGill University, Montreal, Canada

    X
  • Jamie N. Bayona,

    Affiliation: The Dartmouth Center for Health Care Delivery Science, Hanover, New Hampshire, United States of America

    X
  • Mercedes C. Becerra,

    Affiliations: Harvard Medical School, Boston, Massachusetts, United States of America, Partners in Health, Boston, Massachusetts, United States of America

    X
  • Andrea Benedetti,

    Affiliation: Montreal Chest Institute, McGill University, Montreal, Canada

    X
  • Marcos Burgos,

    Affiliation: University of New Mexico School of Medicine, Albuquerque, New Mexico, United States of America

    X
  • Rosella Centis,

    Affiliation: WHO Collaborating Centre for TB and Lung Diseases, Care and Research Institute, Fondazione S. Maugeri, Tradate, Italy

    X
  • Eward D. Chan,

    Affiliation: Denver Veterans Affair Medical Center, Denver, Colorado, United States of America

    X
  • Chen-Yuan Chiang,

    Affiliation: Wan Fang Hospital, School of Medicine-Taipei Medical University, Taiwan

    X
  • Helen Cox,

    Affiliation: Médecins Sans Frontières, Capetown, South Africa

    X
  • Lia D'Ambrosio,

    Affiliation: WHO Collaborating Centre for TB and Lung Diseases, Care and Research Institute, Fondazione S. Maugeri, Tradate, Italy

    X
  • Kathy DeRiemer,

    Affiliation: UC Davis School of Medicine, Davis, California, United States of America

    X
  • Nguyen Huy Dung,

    Affiliation: National TB Control Program, Hanoi, Vietnam

    X
  • Donald Enarson,

    Affiliation: International Union against Tuberculosis and Lung Disease, Paris, France

    X
  • Dennis Falzon,

    Affiliation: World Health Organization, Geneva, Switzerland

    X
  • Katherine Flanagan,

    Affiliation: MRC Laboratories, Banjul, The Gambia

    X
  • Jennifer Flood,

    Affiliation: California Department of Public Health, Sacramento, California, United States of America

    X
  • Maria L. Garcia-Garcia,

    Affiliation: Instituto Nacional de Salud Pública, Mexico, Mexico

    X
  • Neel Gandhi,

    Affiliation: Albert Einstein College of Medicine, Bronx, New York, United States of America

    X
  • Reuben M. Granich,

    Affiliation: World Health Organization, Geneva, Switzerland

    X
  • Maria G. Hollm-Delgado,

    Affiliation: Montreal Chest Institute, McGill University, Montreal, Canada

    X
  • Timothy H. Holtz,

    Affiliation: Thailand MOPH & US CDC Collaboration, Bangkok, Thailand

    X
  • Michael D. Iseman,

    Affiliation: National Jewish Health, Denver, Colorado, United States of America

    X
  • Leah G. Jarlsberg,

    Affiliation: University of California, San Francisco, San Francisco, United States of America

    X
  • Salmaan Keshavjee,

    Affiliation: Harvard Medical School, Boston, Massachusetts, United States of America

    X
  • Hye-Ryoun Kim,

    Affiliation: Korea Cancer Center Hospital, Seoul, Korea

    X
  • Won-Jung Koh,

    Affiliation: Samsung Medical Center, Seoul, Korea

    X
  • Joey Lancaster,

    Affiliation: South African Medical Research Council, Pretoria, South Africa

    X
  • Christophe Lange,

    Affiliation: Medical Clinic, Tuberculosis Center Borstel, Borstel, Germany

    X
  • Wiel C. M. de Lange,

    Affiliation: University Medical Center Groningen, Groningen, The Netherlands

    X
  • Vaira Leimane,

    Affiliation: Clinic of Tuberculosis and Lung Diseases, Riga, Latvia

    X
  • Chi Chiu Leung,

    Affiliation: Tuberculosis and Chest Services, Hong Kong

    X
  • Jiehui Li,

    Affiliation: New York City Health and Mental Hygiene, New York, New York, United States of America

    X
  • Dick Menzies mail,

    Dick.Menzies@McGill.ca

    Affiliation: Montreal Chest Institute, McGill University, Montreal, Canada

    X
  • Giovanni B. Migliori,

    Affiliation: WHO Collaborating Centre for TB and Lung Diseases, Care and Research Institute, Fondazione S. Maugeri, Tradate, Italy

    X
  • Sergey P. Mishustin,

    Affiliation: Tomsk Oblast Tuberculosis Dispensary, Tomsk, Russia

    X
  • Carole D. Mitnick,

    Affiliation: Harvard Medical School, Boston, Massachusetts, United States of America

    X
  • Masa Narita,

    Affiliation: University of Washington, Seattle, Washington, United States of America

    X
  • Philly O'Riordan,

    Affiliation: City Road Medical Centre, London, United Kingdom

    X
  • Madhukar Pai,

    Affiliation: Montreal Chest Institute, McGill University, Montreal, Canada

    X
  • Domingo Palmero,

    Affiliation: Hospital F.J. Muñiz, Buenos Aires, Argentina

    X
  • Seung-kyu Park,

    Affiliation: TB Center, Seoul, Korea

    X
  • Geoffrey Pasvol,

    Affiliation: Imperial College London, London, United Kingdom

    X
  • Jose Peña,

    Affiliation: Universidad Autonoma Madrid, Madrid, Spain

    X
  • Carlos Pérez-Guzmán,

    Affiliation: Instituto de Salud del Estado de Aguascalientes, Mexico, Mexico

    X
  • Maria I. D. Quelapio,

    Affiliation: Tropical Disease Foundation, Makati City, Philippines

    X
  • Alfredo Ponce-de-Leon,

    Affiliation: Instituto Nacional de Ciencias Médicas y de Nutrición “Salvador Zubirán”, Mexico, Mexico

    X
  • Vija Riekstina,

    Affiliation: Clinic of Tuberculosis and Lung Diseases, Riga, Latvia

    X
  • Jerome Robert,

    Affiliation: Bactériologie-Hygiène – UPMC, Paris, France

    X
  • Sarah Royce,

    Affiliation: University of California, San Francisco, San Francisco, United States of America

    X
  • H. Simon Schaaf,

    Affiliation: Stellenbosch University, Stellenbosch, South Africa

    X
  • Kwonjune J. Seung,

    Affiliation: Brigham and Women's Hospital, Boston, Massachusetts, United States of America

    X
  • Lena Shah,

    Affiliation: Montreal Chest Institute, McGill University, Montreal, Canada

    X
  • Tae Sun Shim,

    Affiliation: University of Ulsan College of Medicine, Seoul, Korea

    X
  • Sonya S. Shin,

    Affiliation: Brigham and Women's Hospital, Boston, Massachusetts, United States of America

    X
  • Yuji Shiraishi,

    Affiliation: Fukujuji Hospital, Tokyo, Japan

    X
  • José Sifuentes-Osornio,

    Affiliation: Instituto Nacional de Ciencias Médicas y de Nutrición “Salvador Zubirán”, Mexico, Mexico

    X
  • Giovanni Sotgiu,

    Affiliation: University of Sassari, Sassari, Italy

    X
  • Matthew J. Strand,

    Affiliation: National Jewish Health, Denver, Colorado, United States of America

    X
  • Payam Tabarsi,

    Affiliation: Shaheed Beheshti Medical University, Tehran, Iran

    X
  • Thelma E. Tupasi,

    Affiliation: Tropical Disease Foundation, Makati City, Philippines

    X
  • Robert van Altena,

    Affiliation: University Medical Center Groningen, Groningen, The Netherlands

    X
  • Martie Van der Walt,

    Affiliation: South African Medical Research Council, Pretoria, South Africa

    X
  • Tjip S. Van der Werf,

    Affiliation: University Medical Center Groningen, Groningen, The Netherlands

    X
  • Mario H. Vargas,

    Affiliation: Instituto Nacional de Enfermedades Respiratorias, Mexico, Mexico

    X
  • Pirett Viiklepp,

    Affiliation: National Institute for Health Development, Tallinn, Estonia

    X
  • Janice Westenhouse,

    Affiliation: Center for Infectious Diseases-California Department of Public Health, Sacramento, California, United States of America

    X
  • Wing Wai Yew,

    Affiliation: Grantham Hospital, Hong Kong

    X
  • Jae-Joon Yim, on behalf of the Collaborative Group for Meta-Analysis of Individual Patient Data in MDR-TB,

    Affiliation: Seoul National University College of Medicine, Seoul, Korea

    X
  • Shama D. Ahuja

    All members of the Collaborative Group for Meta-Analysis of Individual Patient Data in MDR-TB are the authors and are listed in the manuscript byline.

    X
  • Published: August 28, 2012
  • DOI: 10.1371/journal.pmed.1001300

About the Authors

Shama D. Ahuja
Bureau of Tuberculosis, New York, New York, United States of America
David Ashkin
A.G. Holley Hospital, Lantana, Florida, United States of America
Monika Avendano
University of Toronto, Toronto, Canada
Rita Banerjee
Mayo Clinic, Rochester, Minnesota, United States of America
Melissa Bauer, Andrea Benedetti, Maria G. Hollm-Delgado, Dick Menzies, Madhukar Pai, Lena Shah
Montreal Chest Institute, McGill University, Montreal, Canada
Jamie N. Bayona
The Dartmouth Center for Health Care Delivery Science, Hanover, New Hampshire, United States of America
Mercedes C. Becerra, Salmaan Keshavjee, Carole D. Mitnick
Harvard Medical School, Boston, Massachusetts, United States of America
Mercedes C. Becerra
Partners in Health, Boston, Massachusetts, United States of America
Marcos Burgos
University of New Mexico School of Medicine, Albuquerque, New Mexico, United States of America
Rosella Centis, Lia D'Ambrosio, Giovanni B. Migliori
WHO Collaborating Centre for TB and Lung Diseases, Care and Research Institute, Fondazione S. Maugeri, Tradate, Italy
Eward D. Chan
Denver Veterans Affair Medical Center, Denver, Colorado, United States of America
Chen-Yuan Chiang
Wan Fang Hospital, School of Medicine-Taipei Medical University, Taiwan
Helen Cox
Médecins Sans Frontières, Capetown, South Africa
Kathy DeRiemer
UC Davis School of Medicine, Davis, California, United States of America
Nguyen Huy Dung
National TB Control Program, Hanoi, Vietnam
Donald Enarson
International Union against Tuberculosis and Lung Disease, Paris, France
Dennis Falzon, Reuben M. Granich
World Health Organization, Geneva, Switzerland
Katherine Flanagan
MRC Laboratories, Banjul, The Gambia
Jennifer Flood
California Department of Public Health, Sacramento, California, United States of America
Maria L. Garcia-Garcia
Instituto Nacional de Salud Pública, Mexico, Mexico
Neel Gandhi
Albert Einstein College of Medicine, Bronx, New York, United States of America
Timothy H. Holtz
Thailand MOPH & US CDC Collaboration, Bangkok, Thailand
Michael D. Iseman, Matthew J. Strand
National Jewish Health, Denver, Colorado, United States of America
Leah G. Jarlsberg, Sarah Royce
University of California, San Francisco, San Francisco, United States of America
Hye-Ryoun Kim
Korea Cancer Center Hospital, Seoul, Korea
Won-Jung Koh
Samsung Medical Center, Seoul, Korea
Joey Lancaster, Martie Van der Walt
South African Medical Research Council, Pretoria, South Africa
Christophe Lange
Medical Clinic, Tuberculosis Center Borstel, Borstel, Germany
Wiel C. M. de Lange, Robert van Altena, Tjip S. Van der Werf
University Medical Center Groningen, Groningen, The Netherlands
Vaira Leimane, Vija Riekstina
Clinic of Tuberculosis and Lung Diseases, Riga, Latvia
Chi Chiu Leung
Tuberculosis and Chest Services, Hong Kong
Jiehui Li
New York City Health and Mental Hygiene, New York, New York, United States of America
Sergey P. Mishustin
Tomsk Oblast Tuberculosis Dispensary, Tomsk, Russia
Masa Narita
University of Washington, Seattle, Washington, United States of America
Philly O'Riordan
City Road Medical Centre, London, United Kingdom
Domingo Palmero
Hospital F.J. Muñiz, Buenos Aires, Argentina
Seung-kyu Park
TB Center, Seoul, Korea
Geoffrey Pasvol
Imperial College London, London, United Kingdom
Jose Peña
Universidad Autonoma Madrid, Madrid, Spain
Carlos Pérez-Guzmán
Instituto de Salud del Estado de Aguascalientes, Mexico, Mexico
Maria I. D. Quelapio, Thelma E. Tupasi
Tropical Disease Foundation, Makati City, Philippines
Alfredo Ponce-de-Leon, José Sifuentes-Osornio
Instituto Nacional de Ciencias Médicas y de Nutrición “Salvador Zubirán”, Mexico, Mexico
Jerome Robert
Bactériologie-Hygiène – UPMC, Paris, France
H. Simon Schaaf
Stellenbosch University, Stellenbosch, South Africa
Kwonjune J. Seung, Sonya S. Shin
Brigham and Women's Hospital, Boston, Massachusetts, United States of America
Tae Sun Shim
University of Ulsan College of Medicine, Seoul, Korea
Yuji Shiraishi
Fukujuji Hospital, Tokyo, Japan
Giovanni Sotgiu
University of Sassari, Sassari, Italy
Payam Tabarsi
Shaheed Beheshti Medical University, Tehran, Iran
Mario H. Vargas
Instituto Nacional de Enfermedades Respiratorias, Mexico, Mexico
Pirett Viiklepp
National Institute for Health Development, Tallinn, Estonia
Janice Westenhouse
Center for Infectious Diseases-California Department of Public Health, Sacramento, California, United States of America
Wing Wai Yew
Grantham Hospital, Hong Kong
Jae-Joon Yim
Seoul National University College of Medicine, Seoul, Korea

Corresponding Author

Email: Dick.Menzies@McGill.ca

Competing Interests

JR is a Consultant for bioMérieux. WWY has been indirectly sponsored to participate in International Conferences by GlaxoSmithKline and Pfizer in the last 3 years. CDM is on the Scientific Advisory Board for Otsuka pharmaceuticals development of OPC67683 (Delaminid), a new anti-TB compound. SK received salary support from the Eli Lilly Foundation as part of funding for the activities of Partners In Health by the Foundation's MDR-TB Partnership. This funder was not involved in the study design; collection, analysis and interpretation of data; writing of the paper; and/or decision to submit for publication. The Partners In Health project in Tomsk received funding from Mr. Tom White, the Open Society Institute, the Bill and Melinda Gates Foundation, and the Global Fund to fight AIDS, Tuberculosis and Malaria. None of these funders were involved in the study design; collection, analysis and interpretation of data; writing of the paper; and/or decision to submit for publication. KD is an unpaid, volunteer member of the New Diagnostics Working Group (NDWG), formed of members of the Stop TB Partnership. The Secretariat of the NDWG is hosted by FIND (Foundation for New Innovative Diagnostics). JB was working as consultant for Otsuka Pharmaceutical for the implementation of clinical trial in Peru. JB was co PI of a NIH grant in Peru, Epidemiology of Tuberculosis. MP and GP are members of the Editorial Board of PLOS Medicine. All other authors have declared that no competing interests exist.

Author Contributions

Performed the experiments. Analyzed the data: SDA DA MA RB MBa JB MCB AB MBu RC EDC CYC HC LD KD NHD DE DF KF JF MLGG NRG RG MGHD THH MDI LGJ SK HRK WJK JLL CL WCMD VL CCL JL DM GBM SM CDM MN PO MP DP SKP GP JMP CPG MIDQ AP VR JR SR HSS KJS LS TSS SSS YS JSO GS MS PT TEP RVA MLV TSV MHV PV JW WWY JJY. Contributed reagents/materials/analysis tools: SDA DA MA RB MBa JB MCB AB MBu RC EDC CYC HC LD KD NHD DE DF KF JF MLGG NRG RG MGHD THH MDI LGJ SK HRK WJK JLL CL WCMD VL CCL JL DM GBM SM CDM MN PO MP DP SKP GP JMP CPG MIDQ AP VR JR SR HSS KJS LS TSS SSS YS JSO GS MS PT TEP RVA MLV TSV MHV PV JW WWY JJY. Wrote the first draft of the manuscript: DM. Contributed to the writing of the manuscript: SDA DA MA RB MBa JB MCB AB MBu RC EDC CYC HC LD KD NHD DE DF KF JF MLGG NRG RG MGHD THH MDI LGJ SK HRK WJK JLL CL WCMD VL CCL JL DM GBM SM CDM MN PO MP DP SKP GP JMP CPG MIDQ AP VR JR SR HSS KJS LS TSS SSS YS JSO GS MS PT TEP RVA MLV TSV MHV PV JW WWY JJY. ICMJE criteria for authorship read and met: SDA DA MA RB MBa JB MCB AB MBu RC EDC CYC HC LD KD NHD DE DF KF JF MLGG NRG RG MGHD THH MDI LGJ SK HRK WJK JLL CL WCMD VL CCL JL DM GBM SM CDM MN PO MP DP SKP GP JMP CPG MIDQ AP VR JR SR HSS KJS LS TSS SSS YS JSO GS MS PT TEP RVA MLV TSV MHV PV JW WWY JJY. Agree with manuscript results and conclusions: SDA DA MA RB MBa JB MCB AB MBu RC EDC CYC HC LD KD NHD DE DF KF JF MLGG NRG RG MGHD THH MDI LGJ SK HRK WJK JLL CL WCMD VL CCL JL DM GBM SM CDM MN PO MP DP SKP GP JMP CPG MIDQ AP VR JR SR HSS KJS LS TSS SSS YS JSO GS MS PT TEP RVA MLV TSV MHV PV JW WWY JJY.