Long-term bedaquiline-related treatment outcomes in patients with extensively drug-resistant tuberculosis from South Africa

Eur Respir J. 2018 May 30;51(5):1800544. doi: 10.1183/13993003.00544-2018. Print 2018 May.

Abstract

Optimal treatment regimens for patients with extensively drug-resistant tuberculosis (XDR-TB) remain unclear. Long-term prospective outcome data comparing XDR-TB regimens with and without bedaquiline from an endemic setting are lacking.We prospectively followed-up 272 South African patients (49.3% HIV-infected; median CD4 count 169 cells·µL-1) with newly diagnosed XDR-TB between 2008 and 2017. Outcomes were compared between those who had not received bedaquiline (pre-2013; n=204) and those who had (post-2013; n=68; 80.9% received linezolid in addition).The 24-month favourable outcome rate was substantially better in the bedaquiline versus the non-bedaquiline group (66.2% (45 out of 68) versus 13.2% (27 out of 204); p<0.001). In addition, the bedaquiline group exhibited reduced 24-month rates of treatment failure (5.9% versus 26.0%; p<0.001) and default (1.5% versus 15.2%; p<0.001). However, linezolid was withdrawn in 32.7% (18 out of 55) of patients in the bedaquiline group because of adverse events. Admission weight >50 kg, an increasing number of anti-TB drugs and bedaquiline were independent predictors of survival (the bedaquiline survival effect remained significant in HIV-infected persons, irrespective of CD4 count).XDR-TB patients receiving a backbone of bedaquiline and linezolid had substantially better favourable outcomes compared to those not using these drugs. These data inform the selection of XDR-TB treatment regimens and roll-out of newer drugs in TB-endemic countries.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Antitubercular Agents / adverse effects
  • Antitubercular Agents / therapeutic use*
  • Diarylquinolines / administration & dosage*
  • Diarylquinolines / adverse effects
  • Extensively Drug-Resistant Tuberculosis / complications
  • Extensively Drug-Resistant Tuberculosis / drug therapy*
  • Extensively Drug-Resistant Tuberculosis / mortality*
  • Female
  • HIV Infections / complications
  • Humans
  • Linezolid / administration & dosage*
  • Linezolid / adverse effects
  • Long-Term Care
  • Male
  • Middle Aged
  • Predictive Value of Tests
  • Prospective Studies
  • South Africa / epidemiology
  • Time Factors
  • Treatment Outcome
  • Withholding Treatment / statistics & numerical data
  • Young Adult

Substances

  • Antitubercular Agents
  • Diarylquinolines
  • bedaquiline
  • Linezolid