Clinical implications of molecular drug resistance testing for Mycobacterium tuberculosis: A TBNET/RESIST-TB consensus statement

J. Dominguez, E. C. Boettger, D. Cirillo, F. Cobelens, K. D. Eisenach, S. Gagneux, D. Hillemann, R. Horsburgh, B. Molina-Moya, S. Niemann, E. Tortoli, A. Whitelaw, C. Lange

Research output: Contribution to journalArticlepeer-review

Abstract

The emergence of drug-resistant strains of Mycobacterium tuberculosis is a challenge to global tuberculosis (TB) control. Although culture-based methods have been regarded as the gold standard for drug susceptibility testing (DST), molecular methods provide rapid information on mutations in the M. tuberculosis genome associated with resistance to anti-tuberculosis drugs.We ascertained consensus on the use of the results of molecular DST for clinical treatment decisions in TB patients. This document has been developed by TBNET and RESIST-TB groups to reach a consensus about reporting standards in the clinical use of molecular DST results. Review of the available literature and the search for evidence included hand-searching journals and searching electronic databases. The panel identified single nucleotide mutations in genomic regions of M. tuberculosis coding for katG, inhA, rpoB, embB, rrs, rpsL and gyrA that are likely related to drug resistance in vivo. Identification of any of these mutations in clinical isolates of M. tuberculosis has implications for the management of TB patients, pending the results of in vitro DST. However, false-positive and false-negative results in detecting resistance-associated mutations in drugs for which there is poor or unproven correlation between phenotypic and clinical drug resistance complicate the interpretation. Reports of molecular DSTresults should therefore include specific information on the mutations identified and provide guidance for clinicians on interpretation and on the choice of the appropriate initial drug regimen.

Original languageEnglish
Pages (from-to)24-42
Number of pages19
JournalInternational Journal of Tuberculosis and Lung Disease
Volume20
Issue number1
DOIs
Publication statusPublished - Jan 1 2016

Keywords

  • Clinician guidance
  • Interpretation
  • Molecular methods

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Infectious Diseases

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