title: Compassionate use of bedaquiline for the treatment of multidrug-resistant and extensively drug-resistant tuberculosis: interim analysis of a French cohort.
abstract: BACKGROUND
  Bedaquiline is a new antibiotic that was approved for the treatment of multidrug-resistant (MDR) tuberculosis. We aimed to evaluate the short-term microbiological efficacy and the tolerability profile of bedaquiline.
  
  
  METHODS
  We performed a retrospective cohort study among patients with MDR tuberculosis receiving bedaquiline for compassionate use between January 2010 and July 2013 and evaluated at 6 months of bedaquiline treatment.
  
  
  RESULTS
  A total of 35 patients with MDR tuberculosis were included in the study. Nineteen (54%) had extensively drug-resistant (XDR) tuberculosis, and 14 (40%) had isolates resistant to fluoroquinolones (Fqs) or second-line injectables. Bedaquiline was associated with a median of 4 (range, 2-5) other drugs, including linezolid in 33 (94%) cases. At 6 months of bedaquiline treatment, culture conversion was achieved in 28 of 29 (97%) cases with culture-positive pulmonary tuberculosis at bedaquiline initiation. Median time to culture conversion was 85 days (range, 8-235 days). Variables independently associated with culture conversion were treatment with a Fq (P = .01), absence of lung cavities (P < .001), and absence of hepatitis C virus infection (P = .001). A total of 7 patients (20%) experienced a ≥60-ms increase in QT interval, leading to bedaquiline discontinuation in 2 (6%) cases. Severe liver enzyme elevation occurred in 2 patients (6%). During the study period, 1 death (3%) occurred and was reported as unrelated to tuberculosis or antituberculosis treatment.
  
  
  CONCLUSIONS
  The use of bedaquiline combined with other active drugs has the potential to achieve high culture conversion rates in complicated MDR and XDR tuberculosis cases, with a reassuring safety profile at 6 months of treatment.
authors.affiliation: Sorbonne Universités, Université P. & M. Curie, Paris 06, CR7 Institut national de la santé et de la recherche médicale, U1135, Centre d'Immunologie et des Maladies Infectieuses, Team E13 (Bactériologie).
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Guglielmetti
authors.affiliation: Sanatorium, Centre Hospitalier de Bligny, Briis-sous-Forges Assistance publique-Hôpitaux de Paris (AP-HP), CHU Raymond Poincaré, Garches.
authors.forename: Damien
authors.initials: D
authors.lastname: Le Dû
authors.affiliation: Sanatorium, Centre Hospitalier de Bligny, Briis-sous-Forges.
authors.forename: Mathilde
authors.initials: M
authors.lastname: Jachym
authors.affiliation: AP-HP, Service des Maladies Infectieuses et Tropicales.
authors.forename: Benoît
authors.initials: B
authors.lastname: Henry
authors.affiliation: Sorbonne Universités, Université P. & M. Curie, Paris 06, CR7 Institut national de la santé et de la recherche médicale, U1135, Centre d'Immunologie et des Maladies Infectieuses, Team E13 (Bactériologie).
authors.forename: Diane
authors.initials: D
authors.lastname: Martin
authors.affiliation: AP-HP, Service des Maladies Infectieuses et Tropicales.
authors.forename: Eric
authors.initials: E
authors.lastname: Caumes
authors.affiliation: Sorbonne Universités, Université P. & M. Curie, Paris 06, CR7 Institut national de la santé et de la recherche médicale, U1135, Centre d'Immunologie et des Maladies Infectieuses, Team E13 (Bactériologie) AP-HP, Centre National de Référence des Mycobactéries et de la Résistance des Mycobactéries aux Antituberculeux, Bactériologie-Hygiène, Hôpitaux Universitaires Pitié Salpêtrière-Charles Foix, Paris, France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Veziris
authors.affiliation: Sanatorium, Centre Hospitalier de Bligny, Briis-sous-Forges.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Métivier
authors.affiliation: Sorbonne Universités, Université P. & M. Curie, Paris 06, CR7 Institut national de la santé et de la recherche médicale, U1135, Centre d'Immunologie et des Maladies Infectieuses, Team E13 (Bactériologie) AP-HP, Centre National de Référence des Mycobactéries et de la Résistance des Mycobactéries aux Antituberculeux, Bactériologie-Hygiène, Hôpitaux Universitaires Pitié Salpêtrière-Charles Foix, Paris, France.
authors.forename: Jérôme
authors.initials: J
authors.lastname: Robert
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000995:Antitubercular Agents / Q000009:adverse effects / Q000627:therapeutic use*; D015331:Cohort Studies; D057176:Compassionate Use Trials; D064687:Diarylquinolines / Q000009:adverse effects / Q000627:therapeutic use*; D064420:Drug-Related Side Effects and Adverse Reactions; D054908:Extensively Drug-Resistant Tuberculosis / Q000188:drug therapy*; D005260:Female; D005602:France; D006801:Humans; D008297:Male; D008875:Middle Aged; D009169:Mycobacterium tuberculosis / Q000302:isolation & purification; D012189:Retrospective Studies; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000995:Antitubercular Agents; D064687:Diarylquinolines; C493870:bedaquiline
keywords: TMC207; bedaquiline; extensively drug-resistant tuberculosis; multidrug-resistant tuberculosis; safety