title: Aggressive regimens for multidrug-resistant tuberculosis decrease all-cause mortality.
abstract: BACKGROUND
  A better understanding of the composition of optimal treatment regimens for multidrug-resistant tuberculosis (MDR-TB) is essential for expanding universal access to effective treatment and for developing new therapies for MDR-TB. Analysis of observational data may inform the definition of an optimized regimen.
  
  
  OBJECTIVE
  This study assessed the impact of an aggressive regimen-one containing at least five likely effective drugs, including a fluoroquinolone and injectable-on treatment outcomes in a large MDR-TB patient cohort.
  
  
  METHODS
  This was a retrospective cohort study of patients treated in a national outpatient program in Peru between 1999 and 2002. We examined the association between receiving an aggressive regimen and the rate of death.
  
  
  RESULTS
  In total, 669 patients were treated with individualized regimens for laboratory-confirmed MDR-TB. Isolates were resistant to a mean of 5.4 (SD 1.7) drugs. Cure or completion was achieved in 66.1% (442) of patients; death occurred in 20.8% (139). Patients who received an aggressive regimen were less likely to die (crude hazard ratio [HR]: 0.62; 95% CI: 0.44,0.89), compared to those who did not receive such a regimen. This association held in analyses adjusted for comorbidities and indicators of severity (adjusted HR: 0.63; 95% CI: 0.43,0.93).
  
  
  CONCLUSIONS
  The aggressive regimen is a robust predictor of MDR-TB treatment outcome. TB policy makers and program directors should consider this standard as they design and implement regimens for patients with drug-resistant disease. Furthermore, the aggressive regimen should be considered the standard background regimen when designing randomized trials of treatment for drug-resistant TB.
authors.affiliation: Department of Global Health and Social Medicine, Harvard Medical School, Boston, Massachusetts, United States of America. carole_mitnick@hms.harvard.edu
authors.forename: Carole D
authors.initials: CD
authors.lastname: Mitnick
authors.forename: Molly F
authors.initials: MF
authors.lastname: Franke
authors.forename: Michael L
authors.initials: ML
authors.lastname: Rich
authors.forename: Felix A
authors.initials: FA
authors.lastname: Alcantara Viru
authors.forename: Sasha C
authors.initials: SC
authors.lastname: Appleton
authors.forename: Sidney S
authors.initials: SS
authors.lastname: Atwood
authors.forename: Jaime N
authors.initials: JN
authors.lastname: Bayona
authors.forename: Cesar A
authors.initials: CA
authors.lastname: Bonilla
authors.forename: Katiuska
authors.initials: K
authors.lastname: Chalco
authors.forename: Hamish S F
authors.initials: HS
authors.lastname: Fraser
authors.forename: Jennifer J
authors.initials: JJ
authors.lastname: Furin
authors.forename: Dalia
authors.initials: D
authors.lastname: Guerra
authors.forename: Rocio M
authors.initials: RM
authors.lastname: Hurtado
authors.forename: Keith
authors.initials: K
authors.lastname: Joseph
authors.forename: Karim
authors.initials: K
authors.lastname: Llaro
authors.forename: Lorena
authors.initials: L
authors.lastname: Mestanza
authors.forename: Joia S
authors.initials: JS
authors.lastname: Mukherjee
authors.forename: Maribel
authors.initials: M
authors.lastname: Muñoz
authors.forename: Eda
authors.initials: E
authors.lastname: Palacios
authors.forename: Epifanio
authors.initials: E
authors.lastname: Sanchez
authors.forename: Kwonjune J
authors.initials: KJ
authors.lastname: Seung
authors.forename: Sonya S
authors.initials: SS
authors.lastname: Shin
authors.forename: Alexander
authors.initials: A
authors.lastname: Sloutsky
authors.forename: Arielle W
authors.initials: AW
authors.lastname: Tolman
authors.forename: Mercedes C
authors.initials: MC
authors.lastname: Becerra
mesh_terms: D000704:Analysis of Variance; D000995:Antitubercular Agents / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D008297:Male; D012189:Retrospective Studies; D013997:Time Factors; D016896:Treatment Outcome; D018088:Tuberculosis, Multidrug-Resistant / Q000188:drug therapy* / Q000401:mortality*
chemical_list: D000995:Antitubercular Agents