title: Improving outcomes for multidrug-resistant tuberculosis: aggressive regimens prevent treatment failure and death.
abstract: BACKGROUND
  Evidence is sparse regarding the optimal construction of regimens to treat multidrug-resistant (MDR) tuberculosis disease due to strains of Mycobacterium tuberculosis resistant to at least both isoniazid and rifampin. Given the low potency of many second-line antituberculous drugs, we hypothesized that an aggressive regimen of at least 5 likely effective drugs during the intensive phase, including a fluoroquinolone and a parenteral agent, would be associated with a reduced risk of death or treatment failure.
  
  
  METHODS
  We conducted a retrospective cohort study of patients initiating MDR tuberculosis treatment between 2000 and 2004 in Tomsk, Russian Federation. We used a multivariate Cox proportional hazards model to assess whether monthly exposure to an aggressive regimen was associated with the risk of death or treatment failure.
  
  
  RESULTS
  Six hundred fourteen individuals with confirmed MDR tuberculosis were eligible for analysis. On multivariable analysis that adjusted for extensively drug-resistant (XDR) tuberculosis-MDR tuberculosis isolates resistant to fluoroquinolones and parenteral agents-we found that monthly exposure to an aggressive regimen was significantly associated with a lower risk of death or treatment failure (hazard ratio, 0.52 [95% confidence interval, .29-.94]; P = .030).
  
  
  CONCLUSIONS
  Receipt of an aggressive treatment regimen was a robust predictor of decreased risk of death or failure during MDR tuberculosis treatment. These findings further support the use of this regimen definition as the benchmark for the standard of care of MDR tuberculosis patients and should be used as the basis for evaluating novel therapies.
authors.affiliation: Division of Infectious Diseases, Brigham and Women's Hospital.
authors.forename: Gustavo E
authors.initials: GE
authors.lastname: Velásquez
authors.affiliation: Department of Global Health and Social Medicine, Harvard Medical School Partners In Health, Boston, Massachusetts Partners In Health, Moscow, Russian Federation Division of Global Health Equity, Brigham and Women's Hospital, Boston, Massachusetts.
authors.forename: Mercedes C
authors.initials: MC
authors.lastname: Becerra
authors.affiliation: Partners In Health, Boston, Massachusetts Partners In Health, Moscow, Russian Federation.
authors.forename: Irina Y
authors.initials: IY
authors.lastname: Gelmanova
authors.affiliation: Partners In Health, Boston, Massachusetts Partners In Health, Moscow, Russian Federation.
authors.forename: Alexander D
authors.initials: AD
authors.lastname: Pasechnikov
authors.affiliation: Partners In Health, Boston, Massachusetts Partners In Health, Moscow, Russian Federation.
authors.forename: Askar
authors.initials: A
authors.lastname: Yedilbayev
authors.affiliation: Partners In Health, Boston, Massachusetts Partners In Health, Moscow, Russian Federation Division of Global Health Equity, Brigham and Women's Hospital, Boston, Massachusetts.
authors.forename: Sonya S
authors.initials: SS
authors.lastname: Shin
authors.affiliation: Tomsk Penitentiary Services, Ministry of Justice.
authors.forename: Yevgeny G
authors.initials: YG
authors.lastname: Andreev
authors.affiliation: Tomsk Oblast Tuberculosis Hospital, Russian Federation.
authors.forename: Galina
authors.initials: G
authors.lastname: Yanova
authors.affiliation: Division of Global Health Equity, Brigham and Women's Hospital, Boston, Massachusetts.
authors.forename: Sidney S
authors.initials: SS
authors.lastname: Atwood
authors.affiliation: Department of Global Health and Social Medicine, Harvard Medical School Partners In Health, Boston, Massachusetts Partners In Health, Moscow, Russian Federation Division of Global Health Equity, Brigham and Women's Hospital, Boston, Massachusetts.
authors.forename: Carole D
authors.initials: CD
authors.lastname: Mitnick
authors.affiliation: Department of Global Health and Social Medicine, Harvard Medical School Partners In Health, Boston, Massachusetts Partners In Health, Moscow, Russian Federation.
authors.forename: Molly F
authors.initials: MF
authors.lastname: Franke
authors.affiliation: Department of Global Health and Social Medicine, Harvard Medical School Partners In Health, Boston, Massachusetts Partners In Health, Moscow, Russian Federation Division of Global Health Equity, Brigham and Women's Hospital, Boston, Massachusetts.
authors.forename: Michael L
authors.initials: ML
authors.lastname: Rich
authors.affiliation: Department of Global Health and Social Medicine, Harvard Medical School Partners In Health, Boston, Massachusetts Partners In Health, Moscow, Russian Federation Division of Global Health Equity, Brigham and Women's Hospital, Boston, Massachusetts.
authors.forename: Salmaan
authors.initials: S
authors.lastname: Keshavjee
mesh_terms: D000328:Adult; D000995:Antitubercular Agents / Q000627:therapeutic use*; D015331:Cohort Studies; D024901:Drug Resistance, Multiple, Bacterial; D004358:Drug Therapy / Q000379:methods; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009169:Mycobacterium tuberculosis / Q000187:drug effects / Q000302:isolation & purification; D012189:Retrospective Studies; D012426:Russia; D016019:Survival Analysis; D016896:Treatment Outcome; D018088:Tuberculosis, Multidrug-Resistant / Q000188:drug therapy* / Q000401:mortality
chemical_list: D000995:Antitubercular Agents
keywords: MDR-TB; clinical outcomes; drug resistance; optimized background regimen; treatment
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