A pilot study on the utility of whole genome sequencing for detecting drug resistance in Mycobacterium tuberculosis...

Whole Genome Sequencing (WGS) comprehensively detects all drug-resistant mutants of Mycobacterium tuberculosis, which can help in the early initiation of specific treatment for the patient. But there is a need to evaluate the performance of WGS in comparison with Line Probe Assays (LPA) and Phenotypic Drug Susceptibility Tests (pDST).

Consecutive sputum samples (58) found positive for Mycobacterium tuberculosis (MTB) by GeneXpert were tested for first-and second-line LPA, pDST and WGS for anti-tubercular drugs.

Of 58, 34 (58.6%) culture isolates were resistant to one or more drugs. Resistance detected by WGS was as follows: Isoniazid 23(39.6%), Rifampicin 21(36.2%), fluoroquinolones 21(36.2%), Ethambutol 18(31%), Linezolid 12(20.6%), Streptomycin 8(13.8%), Kanamycin 6(10.3%), Amikacin and Capreomycin 5(8.6%), Para-amino salicylic acid 1(1.7%) and Ethionamide 1(1.7%). No resistance was detected to Pyrazinamide, Bedaquiline, Clofazimine, Delamanid and Pretomanid. Lineage 3(EAI) was the most predominant 23(39.6%) followed by Lineage 2: 13(22.4%). Intermediate Resistance (IR) and potential novel mutations were observed in a few cases.

Overall accuracy for first-line drugs between pDST vs WGS was >98% &pDST vs LPA >95%, while for second-line drugs accuracy was >96% and >90% respectively. IR and potential novel mutations should be followed up closely to understand their clinical significance.