Long-term outcome and safety of prolonged bedaquiline treatment for multidrug-resistant tuberculosis.
Bedaquiline, a recently approved drug for the treatment of multidrug-resistant tuberculosis (MDR-TB), is recommended for a duration of 24 weeks. There are scarce data on patients treated with this drug outside clinical trials.All MDR-TB patients who started treatment from January 1, 2011 to December 31, 2013 and received ≥30 days of bedaquiline were included in a multicentre observational cohort.Among 45 MDR-TB patients, 53% harboured isolates resistant to both fluoroquinolones and second-line injectables, and 38% harboured isolates resistant to one of these drug classes. Median bedaquiline treatment duration was 361 days and 33 patients (73%) received prolonged (>190 days) bedaquiline treatment. Overall, 36 patients (80%) had favourable outcome, five were lost to follow-up, three died, and one failed and acquired bedaquiline resistance. No cases of recurrence were reported. Severe and serious adverse events were recorded in 60% and 18% of patients, respectively. Values of Fridericia-corrected QT interval (QTcF) >500 ms were recorded in 11% of patients, but neither arrhythmias nor symptomatic cardiac side-effects occurred. Bedaquiline was discontinued in three patients following QTcF prolongation. No significant differences in outcomes or adverse events rates were observed between patients receiving standard and prolonged bedaquiline treatment.Bedaquiline-containing regimens achieved favourable outcomes in a large proportion of patients. Prolonged bedaquiline treatment was overall well tolerated in this cohort.
Sanatorium, Centre Hospitalier de Bligny, Briis-sous-Forges, France lorenzo.guglielmetti@gmail.com.|Sorbonne Université, UPMC Université Paris 06, CR7, INSERM, U1135, Centre d'Immunologie et des Maladies Infectieuses, CIMI, Team E13 (Bactériologie), Paris, France.|Both authors contributed equally to this work.
Lorenzo
0000-0003-0886-9635
L
Guglielmetti
AP-HP, Service des Maladies Infectieuses et Tropicales, Hôpitaux Universitaires Pitié Salpêtrière-Charles Foix, Paris, France.|Both authors contributed equally to this work.
Marie
M
Jaspard
Sanatorium, Centre Hospitalier de Bligny, Briis-sous-Forges, France.
Damien
D
Le Dû
AP-HP, Service des Maladies Infectieuses et Tropicales, Hôpital Bichat Claude Bernard, Paris, France.
Marie
M
Lachâtre
Sanatorium, Centre Hospitalier de Bligny, Briis-sous-Forges, France.|AP-HP, Service de Médecine Aigue Spécialisée, Hôpital Raymond Poincaré, Garches, France.
Dhiba
D
Marigot-Outtandy
Sorbonne Université, UPMC Université Paris 06, CR7, INSERM, U1135, Centre d'Immunologie et des Maladies Infectieuses, CIMI, Team E13 (Bactériologie), Paris, France.|AP-HP, Centre National de Référence des Mycobactéries et de la Résistance des Mycobactéries aux Antituberculeux (CNR-MyRMA), Bactériologie-Hygiène, Hôpitaux Universitaires Pitié Salpêtrière-Charles Foix, Paris, France.
Christine
C
Bernard
Sorbonne Université, UPMC Université Paris 06, CR7, INSERM, U1135, Centre d'Immunologie et des Maladies Infectieuses, CIMI, Team E13 (Bactériologie), Paris, France.|AP-HP, Centre National de Référence des Mycobactéries et de la Résistance des Mycobactéries aux Antituberculeux (CNR-MyRMA), Bactériologie-Hygiène, Hôpitaux Universitaires Pitié Salpêtrière-Charles Foix, Paris, France.
Nicolas
N
Veziris
Sorbonne Université, UPMC Université Paris 06, CR7, INSERM, U1135, Centre d'Immunologie et des Maladies Infectieuses, CIMI, Team E13 (Bactériologie), Paris, France.|AP-HP, Centre National de Référence des Mycobactéries et de la Résistance des Mycobactéries aux Antituberculeux (CNR-MyRMA), Bactériologie-Hygiène, Hôpitaux Universitaires Pitié Salpêtrière-Charles Foix, Paris, France.
Jérôme
J
Robert
AP-HP, Service des Maladies Infectieuses et Tropicales, Hôpital Bichat Claude Bernard, Paris, France.
Yazdan
Y
Yazdanpanah
AP-HP, Service des Maladies Infectieuses et Tropicales, Hôpitaux Universitaires Pitié Salpêtrière-Charles Foix, Paris, France.|Joint senior authors.
Eric
E
Caumes
Sanatorium, Centre Hospitalier de Bligny, Briis-sous-Forges, France.|Joint senior authors.
Mathilde
M
Fréchet-Jachym
D000328:Adult; D000995:Antitubercular Agents / Q000008:administration & dosage* / Q000009:adverse effects; D064687:Diarylquinolines / Q000008:administration & dosage* / Q000009:adverse effects; D064420:Drug-Related Side Effects and Adverse Reactions / Q000453:epidemiology*; D005260:Female; D005602:France; D006801:Humans; D053208:Kaplan-Meier Estimate; D016015:Logistic Models; D008297:Male; D015999:Multivariate Analysis; D009169:Mycobacterium tuberculosis; D012189:Retrospective Studies; D013183:Sputum / Q000382:microbiology; D016896:Treatment Outcome; D018088:Tuberculosis, Multidrug-Resistant / Q000188:drug therapy*
D000995:Antitubercular Agents; D064687:Diarylquinolines; C493870:bedaquiline