GeneXpert MTB/RIF Ultra performance to detect uncommon rpoB mutations in Mycobacterium tuberculosis

BMC Res Notes. 2023 Jul 14;16(1):146. doi: 10.1186/s13104-023-06394-z.

Abstract

Objective: To investigate the performance of GeneXpert MTB/RIF Ultra to accurately detect rifampicin resistance for less common rpoB mutations that potentially confer phenotypic resistance, we tested 28 such Mycobacterium tuberculosis cultures with Xpert Ultra.

Results: They represented 22 different (combinations of) rpoB mutations. Of 28 isolates tested, one was reported by Xpert Ultra as "No rifampicin resistance detected", 8 yielded a "Rifampicin indeterminate" result, and 19 were identified as rifampicin resistant. Overall, our results corroborate previous observations on the "Indeterminate" results for mutations at codon 432, while we add Lys446Gln as additional "Indeterminate" result and Pro439Leu as a false rifampicin-susceptible result. Furthermore, we document other uncommon point mutations and indels across the rpoB gene that are mostly correctly identified as rifampicin resistant by Xpert ultra (V3). Taken together, "Indeterminate" results in Xpert Ultra may indicate underlying rpoB mutations within the rifampicin-resistance determining region and thus increase the post-test probability of rifampicin resistance, albeit to an unknown extent.

Keywords: GeneXpert MTB/RIF Ultra; Rifampicin resistance; Tuberculosis; rpoB.

MeSH terms

  • Antibiotics, Antitubercular* / pharmacology
  • Antibiotics, Antitubercular* / therapeutic use
  • Drug Resistance, Bacterial / genetics
  • Humans
  • Mutation
  • Mycobacterium tuberculosis*
  • Point Mutation
  • Rifampin / pharmacology
  • Sensitivity and Specificity
  • Tuberculosis, Multidrug-Resistant* / diagnosis

Substances

  • Rifampin
  • Antibiotics, Antitubercular