Discordant results between genotypic and phenotypic assays (Xpert MTB/RIF vs. BACTEC MGIT 960 system) for detection of RIF-resistant Mycobacterium tuberculosis isolates in a high burden region

Infect Genet Evol. 2021 Dec:96:105142. doi: 10.1016/j.meegid.2021.105142. Epub 2021 Nov 17.

Abstract

Clinical isolates with discordant phenotypic and genotypic results were submitted to DNA sequencing to identify which were genuinely resistant to rifampin and determine the frequency of silent and disputed mutations in our region. We present the retrospective analysis of all the culture-proven TB cases tested with the Xpert®MTB/RIF assay at the Tuberculosis Clinic and Laboratory of the Tijuana General Hospital, Mexico. Clinical isolates showing a discrepancy between phenotypic and molecular tests were analyzed by DNA sequencing. Thirteen isolates tested as rifampin susceptible on the MGIT system were rifampin-resistant according to Xpert®MTB/RIF assay. DNA sequencing showed that seven (53.8%) isolates had a silent (P514P) mutation; three isolates showed different missense (L511P, D516Y, and S531L) mutations. Three isolates showed no mutations. The existence of heteroresistance and silent or disputed mutations warrants that all rifampin-resistance cases diagnosed with the Xpert®MTB/RIF should be referred to specialized centers for DNA sequencing.

Keywords: MGIT; Mutation; Resistance; Rifampin; Sequencing; Xpert MTB/RIF.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibiotics, Antitubercular / pharmacology*
  • Diagnostic Tests, Routine / instrumentation*
  • Drug Resistance, Bacterial*
  • Genotype
  • Mycobacterium tuberculosis / genetics
  • Mycobacterium tuberculosis / isolation & purification*
  • Phenotype
  • Retrospective Studies
  • Rifampin / pharmacology*
  • Tuberculosis, Multidrug-Resistant / diagnosis*
  • Tuberculosis, Multidrug-Resistant / microbiology

Substances

  • Antibiotics, Antitubercular
  • Rifampin