A comparison of phenotypic and WGS drug susceptibility testing in Mycobacterium tuberculosis isolates from the Republic of Korea.

Background: WGS has significant potential to help tackle the major public health problem of TB. The Republic of Korea has the third highest rates of TB of all Organisation for Economic Cooperation and Development countries but there has been very limited use of WGS in TB to date. Objectives: A retrospective comparison of Mycobacterium tuberculosis (MTB) clinical isolates from 2015 to 2017 from two centres in the Republic of Korea using WGS to compare phenotypic drug susceptibility testing (pDST) and WGS drug susceptibility predictions (WGS-DSP). Methods: Fifty-seven MTB isolates had DNA extracted and were sequenced using the Illumina HiSeq platform. The WGS analysis was performed using bwa mem, bcftools and IQ-Tree; resistance markers were identified using TB profiler. Phenotypic susceptibilities were carried out at the Supranational TB reference laboratory (Korean Institute of Tuberculosis). Results: For first-line antituberculous drugs concordance for rifampicin, isoniazid, pyrazinamide and ethambutol was 98.25%, 92.98%, 87.72% and 85.96%, respectively. The sensitivity of WGS-DSP compared with pDST for rifampicin, isoniazid, pyrazinamide and ethambutol was 97.30%, 92.11%, 78.95% and 95.65%, respectively. The specificity for these first-line antituberculous drugs was 100%, 94.74%, 92.11% and 79.41%, respectively. The sensitivity and specificity for second-line drugs ranged from 66.67% to 100%, and from 82.98% to 100%, respectively. Conclusions: This study confirms the potential role for WGS in drug susceptibility prediction, which would reduce turnaround times. However, further larger studies are needed to ensure current databases of drug resistance mutations are reflective of the TB present in the Republic of Korea.