False detection of rifampicin resistance using Xpert ® MTB/RIF Ultra assay due to an A451V mutation in Mycobacterium tuberculosis .

Autor: Fitzgibbon MM; Irish Mycobacteria Reference Laboratory, St James's Hospital, Dublin, Ireland., Roycroft E; Irish Mycobacteria Reference Laboratory, St James's Hospital, Dublin, Ireland., Sheehan G; Mater Misericordiae University Hospital, Dublin, Ireland., Mc Laughlin AM; Department of Respiratory Medicine, St James's Hospital, Dublin, Ireland., Quintyne KI; Department of Public Health North-East, Meath, Ireland., Brabazon E; Department of Public Health North-East, Meath, Ireland., O'Meara M; Department of Public Health East, Health Service Executive, Dublin, Ireland., Flanagan PR; Irish Mycobacteria Reference Laboratory, St James's Hospital, Dublin, Ireland., Seagar AL; Scottish Mycobacteria Reference Laboratory, Edinburgh, Scotland., Laurenson IF; Scottish Mycobacteria Reference Laboratory, Edinburgh, Scotland., Keane J; Department of Respiratory Medicine, St James's Hospital, Dublin, Ireland., Rogers TR; Irish Mycobacteria Reference Laboratory, St James's Hospital, Dublin, Ireland.
Jazyk: angličtina
Zdroj: JAC-antimicrobial resistance [JAC Antimicrob Resist] 2021 Aug 11; Vol. 3 (3), pp. dlab101. Date of Electronic Publication: 2021 Aug 11 (Print Publication: 2021).
DOI: 10.1093/jacamr/dlab101
Abstrakt: Background: In a 12 month period, three Irish-born adult cases with pulmonary TB were initially diagnosed by Xpert ® MTB/RIF Ultra assay, which detected a rifampicin resistance-conferring mutation prompting treatment as potential MDR cases.
Methods: Further laboratory investigations on the cultured isolates included GenoType MTBDR plus assay, phenotypic drug susceptibility tests using the BD BACTEC MGIT culture system and MIC broth microdilution tests. Sequencing of the rpoB gene was performed using Sanger sequencing and WGS.
Results: Phenotypic drug susceptibility tests determined the isolates to be rifampicin susceptible. Molecular investigations identified an A451V (codon 532) mutation in the Mycobacterium tuberculosis rpoB gene that has not previously been found to cause rifampicin resistance. Genome sequencing revealed that the three isolates' genomes differed by ≤5 SNPs, indicating a high likelihood of recent transmission events. Furthermore, a cluster of six related M. tuberculosis isolates from our in-house typing database showed four were highly related; all were rifampicin susceptible and lacked this mutation.
Conclusions: False detection of rifampicin resistance, albeit rare, should be considered possible with Xpert ® MTB/RIF Ultra assay, particularly in low TB incidence settings. Confirmatory sequencing methods should be performed to prevent the unnecessary use of second-line anti-tuberculous drugs.
(© The Author(s) 2021. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy.)
Databáze: MEDLINE