Recent controversies about MDR and XDR-TB: Global implementation of the WHO shorter MDR-TB regimen and bedaquiline for all with MDR-TB?

Respirology. 2018 Jan;23(1):36-45. doi: 10.1111/resp.13143. Epub 2017 Aug 29.

Abstract

Tuberculosis (TB) is now the biggest infectious disease killer worldwide. Although the estimated incidence of TB has marginally declined over several years, it is out of control in some regions including in Africa. The advent of multidrug-resistant TB (MDR-TB) and extensively drug-resistant TB (XDR-TB) threatens to further destabilize control in several regions of the world. Drug-resistant TB constitutes a significant threat because it underpins almost 25% of global TB mortality, is associated with high morbidity, is a threat to healthcare workers and is unsustainably costly to treat. The advent of highly resistant TB with emerging bacillary resistance to newer drugs has raised further concern. Encouragingly, in addition to preventative strategies, several interventions have recently been introduced to curb the drug-resistant TB epidemic, including newer molecular diagnostic tools, new (bedaquiline and delamanid) and repurposed (linezolid and clofazimine) drugs and shorter and individualized treatment regimens. However, there are several controversies that surround the use of new drugs and regimens, including whether, how and to what extent they should be used, and who specifically should be treated so that outcomes are optimally improved without amplifying the burden of drug resistance, and other potential drawbacks, thus sustaining effectiveness of the new drugs. The equipoise surrounding these controversies is discussed and some recommendations are provided.

Keywords: bedaquiline; extensively drug-resistant tuberculosis; multidrug-resistant tuberculosis; treatment.

Publication types

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

MeSH terms

  • Antitubercular Agents / administration & dosage*
  • Antitubercular Agents / therapeutic use
  • Diarylquinolines / adverse effects
  • Diarylquinolines / therapeutic use*
  • Drug Administration Schedule
  • Drug Therapy, Combination
  • Extensively Drug-Resistant Tuberculosis / drug therapy*
  • Humans
  • Nitroimidazoles / therapeutic use
  • Oxazoles / therapeutic use
  • Tuberculosis, Multidrug-Resistant / drug therapy
  • World Health Organization

Substances

  • Antitubercular Agents
  • Diarylquinolines
  • Nitroimidazoles
  • OPC-67683
  • Oxazoles
  • bedaquiline