title: Treatment outcomes of patients with multidrug-resistant and extensively drug-resistant tuberculosis according to drug susceptibility testing to first- and second-line drugs: an individual patient data meta-analysis.
abstract: BACKGROUND
  Individualized treatment for multidrug-resistant (MDR) tuberculosis and extensively drug-resistant (XDR) tuberculosis depends upon reliable and valid drug susceptibility testing (DST) for pyrazinamide, ethambutol, and second-line tuberculosis drugs. However, the reliability of these tests is uncertain, due to unresolved methodological issues. We estimated the association of DST results for pyrazinamide, ethambutol, and second-line drugs with treatment outcomes in patients with MDR tuberculosis and XDR tuberculosis.
  
  
  METHODS
  We conducted an analysis of individual patient data assembled from 31 previously published cohort studies of patients with MDR and XDR tuberculosis. We used data on patients' clinical characteristics including DST results, treatment received, outcomes, and laboratory methods in each center.
  
  
  RESULTS
  DST methods and treatment regimens used in different centers varied considerably. Among 8955 analyzed patients, in vitro susceptibility to individual drugs was consistently and significantly associated with higher odds of treatment success (compared with resistance to the drug), if that drug was used in the treatment regimen. Various adjusted and sensitivity analyses suggest that this was not explained by confounding. The adjusted odds of treatment success for ethambutol, pyrazinamide, and the group 4 drugs ranged from 1.7 to 2.3, whereas for second-line injectables and fluoroquinolones, odds ranged from 2.4 to 4.6.
  
  
  CONCLUSIONS
  DST for ethambutol, pyrazinamide, and second-line tuberculosis drugs appears to provide clinically useful information to guide selection of treatment regimens for MDR and XDR tuberculosis.
authors.forename: Mayara L
authors.initials: ML
authors.lastname: Bastos
authors.forename: Hamidah
authors.initials: H
authors.lastname: Hussain
authors.forename: Karin
authors.initials: K
authors.lastname: Weyer
authors.forename: Lourdes
authors.initials: L
authors.lastname: Garcia-Garcia
authors.forename: Vaira
authors.initials: V
authors.lastname: Leimane
authors.forename: Chi Chiu
authors.initials: CC
authors.lastname: Leung
authors.forename: Masahiro
authors.initials: M
authors.lastname: Narita
authors.forename: Jose M
authors.initials: JM
authors.lastname: Penã
authors.forename: Alfredo
authors.initials: A
authors.lastname: Ponce-de-Leon
authors.forename: Kwonjune J
authors.initials: KJ
authors.lastname: Seung
authors.forename: Karen
authors.initials: K
authors.lastname: Shean
authors.forename: José
authors.initials: J
authors.lastname: Sifuentes-Osornio
authors.forename: Martie
authors.initials: M
authors.lastname: Van der Walt
authors.forename: Tjip S
authors.initials: TS
authors.lastname: Van der Werf
authors.forename: Wing Wai
authors.initials: WW
authors.lastname: Yew
authors.forename: Dick
authors.initials: D
authors.lastname: Menzies
mesh_terms: D000328:Adult; D000995:Antitubercular Agents / Q000494:pharmacology* / Q000627:therapeutic use*; D054908:Extensively Drug-Resistant Tuberculosis / Q000175:diagnosis* / Q000188:drug therapy*; D005260:Female; D006801:Humans; D008297:Male; D008826:Microbial Sensitivity Tests; D008875:Middle Aged; D016017:Odds Ratio; D012307:Risk Factors; D016896:Treatment Outcome; D018088:Tuberculosis, Multidrug-Resistant / Q000175:diagnosis* / Q000188:drug therapy*; D055815:Young Adult
chemical_list: D000995:Antitubercular Agents
keywords: drug susceptibility test; meta-analysis; multidrug resistant; treatment outcomes; tuberculosis
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