Role of Disputed Mutations in the rpoB Gene in Interpretation of Automated Liquid MGIT Culture Results for Rifampin Susceptibility Testing of Mycobacterium tuberculosis

What is it about?

Tuberculosis control requires fast diagnosis of TB followed by an effective treatment. Delay in treatment initiation may cause additional transmission and inappropriate treatment increases the risk of drug resistance. Molecular assays shorten the time to diagnosis from months to hours when compared to phenotypic tests. Unfortunately discrepancies between genotypic and phenotypic results have emerged and have been causing further delay in patient management. Whereas the presence of specific and well-known mutations in the Rifampicin Resistance Determining Region (RRDR) of the rpoB gene allows easy interpretation of molecular drug susceptibility testing (DST) and consequent clinical decision, less common mutations are more difficult to be interpreted. Specific rpoB mutations associated to low-level rifampicin resistance (“disputed” mutations) are easily missed by some phenotypic methods, thus highlighting discrepancies between genotypic vs phenotypic testing. Given the urgent need for rapid and accurate DST methods, a more extensive understanding of discrepancies between phenotypic and genotypic approaches is needed. To this end, in this study we investigate the reason for discrepancy discrepant cases between DST performed on BACTEC MGIT 960 system and genotypic results. Overall, between 2-3% of rifampicin resistant cases could be missed by MGIT testing. Considering the relevance of such mutations in determining clinically relevant resistance, genotypic DST should be used to replace phenotypic MGIT results when such specific mutations are found.

Featured Image