Abstract
ABSTRACTIn this study, using the Hain GenoType MTBDRsl assays (versions 1 and 2), we found that some nonsynonymous and synonymous mutations in gyrA in Mycobacterium tuberculosis result in systematic false-resistance results to fluoroquinolones by preventing the binding of wild-type probes. Moreover, such mutations can prevent the binding of mutant probes designed for the identification of specific resistance mutations. Although these mutations are likely rare globally, they occur in approximately 7% of multidrug-resistant tuberculosis strains in some settings.
Highlights
As part of its recommendation for a shorter treatment regimen for multidrugresistant tuberculosis (MDR TB), the World Health Organization (WHO) recently endorsed version 2 of the Hain GenoType MTBDRsl as the first genotypic drug susceptibility testing (DST) assay for detecting resistance to fluoroquinolones and to the second-line injectable drugs kanamycin, amikacin, and capreomycin [1,2,3,4,5]
The only documented instance of systematic false-positive fluoroquinolone resistance results with the MTBDRsl was caused by the gyrA Acc/Gcc T80A gCg/gGg A90G double mutations relative to the Mycobacterium tuberculosis H37Rv laboratory strain, given that the A90G mutation prevents the binding of the WT2 band of this assay (Fig. 1) [6,7,8,9]
Several independent studies, which used a variety of techniques, demonstrated that these double mutations do not confer resistance to any of the four fluoroquinolones currently used for the treatment of TB and may even result in hypersusceptibility [6, 7, 9,10,11,12,13,14,15]
Summary
As part of its recommendation for a shorter treatment regimen for multidrugresistant tuberculosis (MDR TB), the World Health Organization (WHO) recently endorsed version 2 of the Hain GenoType MTBDRsl as the first genotypic drug susceptibility testing (DST) assay for detecting resistance to fluoroquinolones and to the second-line injectable drugs kanamycin, amikacin, and capreomycin [1,2,3,4,5]. The only documented instance of systematic false-positive fluoroquinolone resistance results with the MTBDRsl was caused by the gyrA Acc/Gcc T80A gCg/gGg A90G double mutations relative to the Mycobacterium tuberculosis H37Rv laboratory strain, given that the A90G mutation prevents the binding of the WT2 band of this assay (Fig. 1) [6,7,8,9].
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