How should discordance between molecular and growth-based assays for rifampicin resistance be investigated?

S. Hofmann-Thiel, H. Hoffmann, D. Hillemann, L. Rigouts, A. Van Deun, K. Kranzer

Research output: Contribution to journalA1: Web of Science-article

Abstract

Molecular tests to detect the presence of Mycobacterium tuberculosis and genetic polymorphisms in the rpoB gene conferring resistance to rifampicin (RMP) have become integral parts of tuberculosis diagnostics worldwide. These assays are often performed sequentially or in parallel to phenotypic drug susceptibility testing. Discordances between molecular and phenotypic tests invariably occur. Root causes range from pre-, post- and analytic errors to co-existence of non-tuberculous mycobacteria, silent mutations, mutations outside the 81 base-pair RMP resistance-determining region, non - canonical mutations conferring increased minimal inhibitory concentrations below the critical concentration in some phenotypic drug susceptibility tests, and heteroresistance. Resolving discordant results is challenging. This guide aims to assist both clinicians and microbiologists in interpreting discordances by providing a structured approach to manage further investigations. Case scenarios are discussed, including the likelihood of occurrence.

Original languageEnglish
JournalInternational Journal of Tuberculosis and Lung Disease
Volume21
Issue number7
Pages (from-to)721-726
Number of pages6
ISSN1027-3719
DOIs
Publication statusPublished - 2017

Keywords

  • RMP
  • molecular diagnostics
  • Xpert (R) MTB/RIF
  • phenotypic DST
  • tuberculosis
  • XPERT(R) MTB/RIF ASSAY
  • SUSCEPTIBILITY TEST METHODS
  • MYCOBACTERIUM-TUBERCULOSIS
  • CULTURE-SYSTEM
  • RPOB MUTATIONS
  • HETERORESISTANCE
  • IMPLEMENTATION
  • PERFORMANCE
  • INFECTIONS
  • SWAZILAND

Cite this