Individualizing management of extensively drug-resistant tuberculosis: diagnostics, treatment, and biomarkers

Expert Rev Anti Infect Ther. 2017 Jan;15(1):11-21. doi: 10.1080/14787210.2017.1247692. Epub 2016 Oct 24.

Abstract

Success rates for treatment of extensively drug resistant tuberculosis (XDR-TB) are low due to limited treatment options, delayed diagnosis and inadequate health care infrastructure. Areas covered: This review analyses existing programmes of prevention, diagnosis and treatment of XDR-TB. Improved diagnostic procedures and rapid molecular tests help to select appropriate drugs and dosages. Drugs dosages can be further tailored to the specific conditions of the patient based on quantitative susceptibility testing of the M. tuberculosis isolate and use of therapeutic drug monitoring. Pharmacovigilance is important for preserving activity of the novel drugs bedaquiline and delamanid. Furthermore, biomarkers of treatment response must be developed and validated to guide therapeutic decisions. Expert commentary: Given the currently poor treatment outcomes and the association of XDR-TB with HIV in endemic regions, a more patient oriented approach regarding diagnostics, drug selection and tailoring and treatment evaluation will improve treatment outcome. The different areas of expertise should be covered by a multidisciplinary team and may involve the transition of patients from hospitalized to home or community-based treatment.

Keywords: Extensive drug resistant tuberculosis; biomarkers; diagnostics; individualised treatment; therapeutic drug monitoring; treatment.

Publication types

  • Review

MeSH terms

  • Antitubercular Agents / administration & dosage
  • Antitubercular Agents / adverse effects
  • Antitubercular Agents / therapeutic use
  • Biomarkers / analysis
  • Clinical Trials as Topic
  • Coinfection / diagnosis
  • Coinfection / drug therapy
  • Diarylquinolines / administration & dosage
  • Diarylquinolines / adverse effects
  • Diarylquinolines / therapeutic use*
  • Extensively Drug-Resistant Tuberculosis / diagnosis*
  • Extensively Drug-Resistant Tuberculosis / drug therapy*
  • Extensively Drug-Resistant Tuberculosis / epidemiology
  • HIV Infections / drug therapy
  • HIV Infections / epidemiology
  • Humans
  • Mycobacterium tuberculosis / drug effects*
  • Mycobacterium tuberculosis / metabolism
  • Nitroimidazoles / administration & dosage
  • Nitroimidazoles / adverse effects
  • Nitroimidazoles / therapeutic use
  • Oxazoles / administration & dosage
  • Oxazoles / adverse effects
  • Oxazoles / therapeutic use
  • Practice Guidelines as Topic
  • Precision Medicine*

Substances

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