title: Risk factors and mortality associated with default from multidrug-resistant tuberculosis treatment.
abstract: BACKGROUND
  Completing treatment for multidrug-resistant (MDR) tuberculosis (TB) may be more challenging than completing first-line TB therapy, especially in resource-poor settings. The objectives of this study were to (1) identify risk factors for default from MDR TB therapy (defined as prolonged treatment interruption), (2) quantify mortality among patients who default from treatment, and (3) identify risk factors for death after default from treatment.
  
  
  METHODS
  We performed a retrospective chart review to identify risk factors for default from MDR TB therapy and conducted home visits to assess mortality among patients who defaulted from such therapy.
  
  
  RESULTS
  Sixty-seven (10.0%) of 671 patients defaulted from MDR TB therapy. The median time to treatment default was 438 days (interquartile range, 152-710 days), and 27 (40.3%) of the 67 patients who defaulted from treatment had culture-positive sputum at the time of default. Substance use (hazard ratio, 2.96; 95% confidence interval, 1.56-5.62; P = .001), substandard housing conditions (hazard ratio, 1.83; 95% confidence interval, 1.07-3.11; P = .03), later year of enrollment (hazard ratio, 1.62, 95% confidence interval, 1.09-2.41; P = .02), and health district (P = .02) predicted default from therapy in a multivariable analysis. Severe adverse events did not predict default from therapy. Forty-seven (70.1%) of 67 patients who defaulted from therapy were successfully traced; of these, 25 (53.2%) had died. Poor bacteriologic response, <1 year of treatment at the time of default, low education level, and diagnosis with a psychiatric disorder significantly predicted death after default in a multivariable analysis.
  
  
  CONCLUSIONS
  The proportion of patients who defaulted from MDR TB treatment was relatively low. The large proportion of patients who had culture-positive sputum at the time of treatment default underscores the public health importance of minimizing treatment default. Prognosis for patients who defaulted from therapy was poor. Interventions aimed at preventing treatment default may reduce TB-related mortality.
authors.affiliation: Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts 02115, USA. mfranke@hsph.harvard.edu
authors.forename: Molly F
authors.initials: MF
authors.lastname: Franke
authors.forename: Sasha C
authors.initials: SC
authors.lastname: Appleton
authors.forename: Jaime
authors.initials: J
authors.lastname: Bayona
authors.forename: Fernando
authors.initials: F
authors.lastname: Arteaga
authors.forename: Eda
authors.initials: E
authors.lastname: Palacios
authors.forename: Karim
authors.initials: K
authors.lastname: Llaro
authors.forename: Sonya S
authors.initials: SS
authors.lastname: Shin
authors.forename: Mercedes C
authors.initials: MC
authors.lastname: Becerra
authors.forename: Megan B
authors.initials: MB
authors.lastname: Murray
authors.forename: Carole D
authors.initials: CD
authors.lastname: Mitnick
mesh_terms: D000328:Adult; D000995:Antitubercular Agents / Q000009:adverse effects / Q000627:therapeutic use*; D024901:Drug Resistance, Multiple, Bacterial; D004493:Education; D005260:Female; D006801:Humans; D008297:Male; D001523:Mental Disorders / Q000150:complications; D009169:Mycobacterium tuberculosis / Q000187:drug effects* / Q000302:isolation & purification; D012189:Retrospective Studies; D012307:Risk Factors; D012959:Socioeconomic Factors; D013183:Sputum / Q000382:microbiology; D019966:Substance-Related Disorders; D013997:Time Factors; D016312:Treatment Refusal; D018088:Tuberculosis, Multidrug-Resistant / Q000188:drug therapy* / Q000401:mortality*
chemical_list: D000995:Antitubercular Agents