Review article

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

Shama D. AhujaDavid AshkinMonika AvendanoUniversity of Toronto, Toronto, CanadaRita BanerjeeMayo Clinic, Rochester, Minnesota, United States of AmericaMelissa BauerMontreal Chest Institute, McGill University, Montreal, CanadaJ BayonaThe Dartmouth Center for Health Care Delivery Science, Hanover, New Hampshire, United States of AmericaMercedes C. BecerraHarvard Medical School, Boston, Massachusetts, United States of AmericaAndrea BenedettiMontreal Chest Institute, McGill University, Montreal, CanadaMarcos BurgosUniversity of New Mexico School of Medicine, Albuquerque, New Mexico, United States of AmericaRosella CentisWHO Collaborating Centre for TB and Lung Diseases, Care and Research Institute, Fondazione S. Maugeri, Tradate, ItalyEward D. ChanDenver Veterans Affair Medical Center, Denver, Colorado, United States of AmericaChen‐Yuan ChiangWan Fang Hospital, School of Medicine-Taipei Medical University, TaiwanHelen CoxMédecins Sans Frontières, Capetown, South AfricaLia D’AmbrosioWHO Collaborating Centre for TB and Lung Diseases, Care and Research Institute, Fondazione S. Maugeri, Tradate, ItalyKathryn DeRiemerUC Davis School of Medicine, Davis, California, United States of AmericaNguyen Huy DungDonald A. EnarsonInternational Union against Tuberculosis and Lung Disease, Paris, FranceDennis FalzonWorld Health Organization, Geneva, SwitzerlandKatherine FlanaganMRC Laboratories, Banjul, The GambiaJennifer FloodCalifornia Department of Public Health, Sacramento, California, United States of AmericaMaria L. Garcia-GarciaInstituto Nacional de Salud Pública, Mexico, MexicoNeel R. GandhiAlbert Einstein College of Medicine, Bronx, New York, United States of AmericaReuben GranichWorld Health Organization, Geneva, SwitzerlandMaria-Graciela Hollm-DelgadoMontreal Chest Institute, McGill University, Montreal, CanadaTimothy H. HoltzMichael D. IsemanNational Jewish Health, Denver, Colorado, United States of AmericaLeah G. JarlsbergUniversity of California, San Francisco, San Francisco, United States of AmericaSalmaan KeshavjeeHarvard Medical School, Boston, Massachusetts, United States of AmericaHye-Ryoun KimWon‐Jung KohSamsung Medical Center, Seoul, KoreaJoey LancasterSouth African Medical Research Council, Pretoria, South AfricaChristoph LangeMedical Clinic, Tuberculosis Center Borstel, Borstel, GermanyWiel C.M. de LangeUniversity Medical Center Groningen, Groningen, The NetherlandsVaira LeimaneChi Chiu LeungTuberculosis and Chest Services, Hong KongJiehui LiNew York City Health and Mental Hygiene, New York, New York, United States of AmericaDick MenziesMontreal Chest Institute, McGill University, Montreal, CanadaGiovanni Battista MiglioriWHO Collaborating Centre for TB and Lung Diseases, Care and Research Institute, Fondazione S. Maugeri, Tradate, ItalySergey P. MishustinTomsk Oblast Tuberculosis Dispensary, Tomsk, RussiaCarole D. MitnickHarvard Medical School, Boston, Massachusetts, United States of AmericaMasahiro NaritaUniversity of Washington, Seattle, Washington, United States of AmericaPhilly O'RiordanCity Road Medical Centre, London, United KingdomMadhukar PaiMontreal Chest Institute, McGill University, Montreal, CanadaDomingo PalmeroHospital F.J. Muñiz, Buenos Aires, ArgentinaSeung-Kyu ParkGeoffrey PasvolImperial College London, London, United KingdomJosé M. PeñaUniversidad Autonoma Madrid, Madrid, SpainCarlos Pérez-GuzmánInstituto de Salud del Estado de Aguascalientes, Mexico, MexicoMaria Imelda QuelapioTropical Disease Foundation, Makati City, PhilippinesAlfredo Ponce‐de‐LeónInstituto Nacional de Ciencias Médicas y de Nutrición “Salvador Zubirán”, Mexico, MexicoVija RiekstiņaJ. RobertBactériologie-Hygiène – UPMC, Paris, FranceSarah RoyceUniversity of California, San Francisco, San Francisco, United States of AmericaH. Simon SchaafStellenbosch University, Stellenbosch, South AfricaKwonjune J. SeungBrigham and Women's Hospital, Boston, Massachusetts, United States of AmericaLena ShahMontreal Chest Institute, McGill University, Montreal, CanadaTae Sun ShimUniversity of Ulsan College of Medicine, Seoul, KoreaSonya ShinBrigham and Women's Hospital, Boston, Massachusetts, United States of AmericaYuji ShiraishiFukujuji Hospital, Tokyo, JapanJosé Sifuentes‐OsornioInstituto Nacional de Ciencias Médicas y de Nutrición “Salvador Zubirán”, Mexico, MexicoGiovanni SotgiuUniversity of Sassari, Sassari, ItalyMatthew StrandNational Jewish Health, Denver, Colorado, United States of AmericaPayam TabarsiShaheed Beheshti Medical University, Tehran, IranThelma E. TupasiTropical Disease Foundation, Makati City, PhilippinesRobert van AltenaUniversity Medical Center Groningen, Groningen, The NetherlandsMartie van der WaltSouth African Medical Research Council, Pretoria, South AfricaTjip S. van der WerfUniversity Medical Center Groningen, Groningen, The NetherlandsMario H. VargasInstituto Nacional de Enfermedades Respiratorias, Mexico, MexicoPirett ViikleppNational Institute for Health Development, Tallinn, EstoniaJanice WestenhouseCenter for Infectious Diseases-California Department of Public Health, Sacramento, California, United States of AmericaWing Wai YewGrantham Hospital, Hong KongJae‐Joon YimSeoul National University College of Medicine, Seoul, KoreaCollaborative Group for Meta-Analysis of Individual Patient Data in MDR-TB

2012en

ABI

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.

Identifiers

DOI: 10.1371/journal.pmed.1001300

Citations and references

Cited by 70 references

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