Journal
INTERNATIONAL JOURNAL OF INFECTIOUS DISEASES
Volume 113, Issue -, Pages S48-S54Publisher
ELSEVIER SCI LTD
DOI: 10.1016/j.ijid.2021.03.033
Keywords
Whole genome sequencing; Mycobacterium tuberculosis; Drug Resistance; Tuberculosis; Lineage; Multi-drug resistant tuberculosis
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Funding
- NSW Health through the Translational Research Grant Scheme
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Routine whole genome sequencing (WGS) provides better guidance for drug resistance management of Mycobacterium tuberculosis compared to commercial genotypic assays. WGS identified additional drug resistance mutations not detected by conventional phenotypic DST, leading to a significant increase in drug resistance detection.
Routine whole genome sequencing (WGS) of pathogens is becoming more feasible as sequencing costs decrease and access to benchtop sequencing equipment and bioinformatics pipelines increases. This study examined the added value gained from implementing routine WGS of all Mycobacterium tuberculosis isolates in New South Wales, Australia. Drug resistance markers inferred from WGS data were compared to commercial genotypic drug susceptibility testing (DST) assays and conventional phenotypic DST in all isolates sequenced between 2016 and 2019. Of the 1107 clinical M. tuberculosis isolates sequenced, 29 (2.6%) were multi-drug resistant (MDR); most belonged to Beijing (336; 30.4%) or East-African Indian (332; 30%) lineages. Compared with conventional phenotypic DST, WGS identified an additional 1% of isolates which were likely drug resistant, explained by mutations previously associated with treatment failure and mixed bacterial populations. However, WGS provided a 20% increase in drug resistance detection in comparison with commercial genotypic assays by identifying mutations outside of the classic resistance determining regions in rpoB, inhA, katG, pncA and embB genes. Gains in drug resistance detection were significant (p = 0.0137, paired t-test), but varied substantially for different phylogenetic lineages. In low incidence settings, routine WGS of M. tuberculosis provides better guidance for person-centered management of drug resistant tuberculosis than commercial genotypic assays. (C) 2021 Published by Elsevier Ltd on behalf of International Society for Infectious Diseases.
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