title: Identification of patients who could benefit from bedaquiline or delamanid: a multisite MDR-TB cohort study.
abstract: BACKGROUND
  The World Health Organization recommends adding bedaquiline or delamanid to multidrug-resistant tuberculosis (MDR-TB) regimens for which four effective drugs are not available, and delamanid for patients at high risk of poor outcome.
  
  
  OBJECTIVE
  To identify patients at risk of unfavourable outcomes who may benefit from the new drugs.
  
  
  METHODS
  Retrospective cohort study of treatment outcomes involving four to five effective drugs for 15-24 months in programmes in Uzbekistan, Georgia, Armenia, Swaziland and Kenya between 2001 and 2011.
  
  
  RESULTS
  Of 1433 patients, 48.5% had body mass index (BMI) <18.5 kg/m(2), 72.9% had a high bacillary load, 16.7% were resistant to two injectables, 2.9% were resistant to ofloxacin (OFX) and 3.0% had extensively drug-resistant TB (XDR-TB). Treatment success ranged from 59.7% (no second-line resistance) to 27.0% (XDR-TB). XDR-TB (aOR 8.16, 95%CI 3.22-20.64), resistance to two injectables (aOR 1.90, 95%CI 1.00-3.62) or OFX (aOR 5.56, 95%CI 2.15-14.37), past incarceration (aOR 1.88, 95%CI 1.11-3.2), history of second-line treatment (aOR 3.24, 95%CI 1.53-6.85), low BMI (aOR 2.22, 95%CI 1.56-3.12) and high bacillary load (aOR 2.32, 95%CI 1.15-4.67) were associated with unfavourable outcomes. Patients started on capreomycin rather than kanamycin were more likely to have an unfavourable outcome (aOR 1.54, 95%CI 1.04-2.28).
  
  
  CONCLUSIONS
  In our cohort, patients who may benefit from bedaquiline and delamanid represented up to two thirds of all MDR-TB patients.
authors.affiliation: Epicentre, Paris, France; Institut de Recherche pour le Développement UMI 233 TransVIHMI - UM - INSERM U117, Montpellier, France.
authors.forename: M
authors.initials: M
authors.lastname: Bonnet
authors.affiliation: Epicentre, Paris, France.
authors.forename: M
authors.initials: M
authors.lastname: Bastard
authors.affiliation: Médecins Sans Frontières (MSF), London, UK.
authors.forename: P
authors.initials: P
authors.lastname: du Cros
authors.affiliation: Ministry of Health of Karakalpakstan, Nukus, Uzbekistan.
authors.forename: A
authors.initials: A
authors.lastname: Khamraev
authors.affiliation: Division of Leprosy Tuberculosis and Lung Disease, Nairobi, Kenya.
authors.forename: K
authors.initials: K
authors.lastname: Kimenye
authors.affiliation: Abkhazian National Tuberculosis Programme, Sukhumi, Abkhazia.
authors.forename: S
authors.initials: S
authors.lastname: Khurkhumal
authors.affiliation: Armenian National Tuberculosis Programme, Yerevan, Armenia.
authors.forename: A
authors.initials: A
authors.lastname: Hayrapetyan
authors.affiliation: Ministry of Health of Swaziland, Mbabane, Swaziland.
authors.forename: D
authors.initials: D
authors.lastname: Themba
authors.affiliation: MSF, Geneva, Switzerland.
authors.forename: A
authors.initials: A
authors.lastname: Telnov
authors.affiliation: Epicentre, Paris, France.
authors.forename: E
authors.initials: E
authors.lastname: Sanchez-Padilla
authors.affiliation: MSF, Paris, France.
authors.forename: C
authors.initials: C
authors.lastname: Hewison
authors.affiliation: MSF, Paris, France.
authors.forename: F
authors.initials: F
authors.lastname: Varaine
mesh_terms: D000328:Adult; D000995:Antitubercular Agents / Q000627:therapeutic use*; D058491:Bacterial Load; D064687:Diarylquinolines / Q000627:therapeutic use*; D024901:Drug Resistance, Multiple, Bacterial; D004359:Drug Therapy, Combination; D013541:Eswatini; D005260:Female; D006801:Humans; D007630:Kenya; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009169:Mycobacterium tuberculosis / Q000187:drug effects* / Q000254:growth & development; D009593:Nitroimidazoles / Q000627:therapeutic use*; D016017:Odds Ratio; D010080:Oxazoles / Q000627:therapeutic use*; D018579:Patient Selection; D012189:Retrospective Studies; D012307:Risk Factors; D013997:Time Factors; D016896:Treatment Outcome; D018088:Tuberculosis, Multidrug-Resistant / Q000175:diagnosis / Q000188:drug therapy* / Q000382:microbiology; D014586:USSR; D055815:Young Adult
chemical_list: D000995:Antitubercular Agents; D064687:Diarylquinolines; D009593:Nitroimidazoles; C516022:OPC-67683; D010080:Oxazoles; C493870:bedaquiline