GeneXpert Ultra performance to detect uncommon rpoB mutations in Mycobacterium tuberculosis

Abstract Objective: To investigate the performance of GeneXpert MTB/RIF Ultra to accurately detect rifampicin resistance (RR) for less common rpoB mutations that potentially confer phenotypic RR, 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 R detected” (RS), 8 yielded an “R Indeterminate” result, and 19 were identified as RR. 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-RS result. Furthermore, we document other uncommon SNPs and indels across the rpoB gene that are mostly correctly identified as RR 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.