Whole-genome sequencing of clinical isolates from tuberculosis patients in India: real-world data indicates a high proportion of pre-XDR cases

• DOI: 10.1128/spectrum.02770-23
• Publication Date: 2024-04-10T13:00:19Z
• Authors: Aparna Bhanushali; Sachin Atre; Preethi Nair; Geethanjali Anilk...; Sanchi Shah; Sanjana Kuruwa; Amrutraj Zade; Chaitali Nikam; Mangala Gomare; Anirvan Chatterjee
• Keywords: rpoB; Pyrazinamide; Bedaquiline; Extensively drug-resistant tuberculosis; INHA; Linezolid

ABSTRACT Treatment decisions for tuberculosis (TB) in the absence of full drug-susceptibility data can result amplifying resistance and may compromise treatment outcomes. Genomics Mycobacterium ( M.tb ) from clinical samples enables detection drug to multiple drugs. We performed whole-genome sequencing (WGS) 600 patients with identify drug-resistance profile mutation spectrum. documented reasons reported by clinicians referral. WGS identified a high proportion (51%) pre-extensively drug-resistant (pre-XDR) cases followed multidrug-resistant (MDR-TB) (15.5%). This correlates primary reason referral, as non-response first-line (67%) failure or rifampicin (14%). Multivariate analysis indicated that all young age groups P < 0.05), male gender Beijing strain 0.01) were significant independent predictors MDR-TB MDR-TB+ [pre-extensively (XDR-TB) XDR-TB]. Ser315Thr (72.5%) inhA gene Ser450Leu rpoB (65.5%) most prevalent mutations, resistance-conferring mutations pyrazinamide (41%) streptomycin (61.33%). Mutations outside resistance-determining region (RRDR), Ile491Phe Val170Phe, seen 1.3% cases; disputed (Asp435Tyr, His445Asn, His445Leu, Leu430Pro) 6% cases, newer drugs such bedaquiline linezolid 1.0% 7.5% respectively. study on highlights there is pre-XDR emerging drugs; ongoing transmission these strains cause serious threat public health; effectively support precision medicine TB. IMPORTANCE The current based real-world TB India. indicates clinicians’ sending WGS, which difficult-to-treat and/or relapse failure. reports pre-XDR-TB warrant policy makers’ attention. It reflects iterative nature diagnostic tests under programmatic conditions leads delays appropriate diagnosis empirical treatment. India had an estimated burden 2.95 million 2020 135,000 cases. However, profiles remains disproportionately poorly represented. adds body isolated India, RRDR, linezolid.