High treatment success rate for multidrug-resistant and extensively drug-resistant tuberculosis using a bedaquiline-containing treatment regimen

Eur Respir J. 2018 Dec 20;52(6):1801528. doi: 10.1183/13993003.01528-2018. Print 2018 Dec.

Abstract

South African patients with rifampicin-resistant tuberculosis (TB) and resistance to fluoroquinolones and/or injectable drugs (extensively drug-resistant (XDR) and preXDR-TB) were granted access to bedaquiline through a clinical access programme with strict inclusion and exclusion criteria.PreXDR-TB and XDR-TB patients were treated with 24 weeks of bedaquiline within an optimised, individualised background regimen that could include levofloxacin, linezolid and clofazimine as needed. 200 patients were enrolled: 87 (43.9%) had XDR-TB, 99 (49.3%) were female and the median age was 34 years (interquartile range (IQR) 27-42). 134 (67.0%) were living with HIV; the median CD4+ count was 281 cells·μL-1 (IQR 130-467) and all were on antiretroviral therapy.16 out of 200 patients (8.0%) did not complete 6 months of bedaquiline: eight were lost to follow-up, six died, one stopped owing to side effects and one was diagnosed with drug-sensitive TB. 146 out of 200 patients (73.0%) had favourable outcomes: 139 (69.5%) were cured and seven (3.5%) completed treatment. 25 patients (12.5%) died, 20 (10.0%) were lost from treatment and nine (4.5%) had treatment failure. 22 adverse events were attributed to bedaquiline, including a QT interval corrected using the Fridericia formula (QTcF) >500 ms (n=5), QTcF increase >50 ms from baseline (n=11) and paroxysmal atrial flutter (n=1).Bedaquiline added to an optimised background regimen was associated with a high rate of successful treatment outcomes for this preXDR-TB and XDR-TB cohort.

Publication types

  • Observational Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Anti-HIV Agents / administration & dosage
  • Antitubercular Agents / administration & dosage
  • Clofazimine / administration & dosage
  • Diarylquinolines / administration & dosage*
  • Diarylquinolines / adverse effects
  • Drug Resistance, Bacterial
  • Drug Therapy, Combination
  • Extensively Drug-Resistant Tuberculosis / drug therapy*
  • Female
  • Fluoroquinolones / therapeutic use
  • HIV Infections / complications
  • HIV Infections / drug therapy
  • Humans
  • Levofloxacin / administration & dosage
  • Linezolid / administration & dosage
  • Male
  • Middle Aged
  • Poisson Distribution
  • South Africa
  • Treatment Outcome
  • Tuberculosis, Multidrug-Resistant / drug therapy*

Substances

  • Anti-HIV Agents
  • Antitubercular Agents
  • Diarylquinolines
  • Fluoroquinolones
  • Levofloxacin
  • bedaquiline
  • Clofazimine
  • Linezolid