Xpert MTB/XDR performance in non-sputum samples for diagnosis of drug-resistant tuberculosis at a North Indian tertiary care center.

UNLABELLED: Rapid diagnosis of drug-resistant tuberculosis (DR-TB) is very challenging, specifically in extra-pulmonary TB specimens. The current study was performed on non-sputum specimens. All specimens were subjected on Xpert MTB/RIF Ultra followed by Xpert MTB/XDR, Ziehl-Neelsen (ZN) Staining, liquid culture, line probe assay (LPA), and drug susceptibility testing (DST). Out of 1,152 non-sputum specimens, 218 were observed to be positive on Xpert MTB/RIF Ultra and were selected for further investigation. From 218 MTBC positive, Xpert MTB/XDR yielded 174 (79.8%) positive while 25 (11.5%) were negative. On comparison with reference standards, ZN smear, and culture, the sensitivity was 100% and 95.51% with specificity of 17.86% and 18.63%, respectively. DST sensitivity and specificity were 84.62% and 96.61%, 83.33% and 96.88%, 50% and 98.75%, 50% and 98.72%, and 50% and 98.75%, respectively, for isoniazid, fluoroquinolones, amikacin, kanamycin, and capreomycin in culture positive specimens. The sensitivity and specificity of Xpert MTB/XDR assay, compared with LPA (MTBDRplus and MTBDRsl), was between 94.12%-100% and 98.39%-100%, respectively. Sensitivity and specificity of Xpert MTB/XDR matched with culture-DST and LPA results for all the tested drugs. Its placement in diagnostic algorithms with Xpert MTB/RIF Ultra under National TB Programs will enhance patient outcome by providing prompt switch to a DST guided treatment regimen.

IMPORTANCE: This study provides crucial evidence supporting the use of Xpert MTB/XDR for rapid detection of DR-TB in non-sputum specimens including extra-pulmonary specimens, where diagnosis remains challenging due to paucibacillary in nature. By demonstrating high sensitivity and specificity compared with culture-DST and LPA, the assay shows strong potential to be integrated into the National TB Elimination Program (NTEP) diagnostic algorithm. Early detection of resistance to isoniazid, fluoroquinolones, and second-line injectables enables timely transition to DST-guided treatment, reducing delays and improving patient outcomes. The findings highlight the assay's ability to reduce dependency on conventional laboratory-based DST, shortening turnaround time and strengthening decentralized diagnostic capacity. This study provides programmatic evidence for policy-level adoption, supporting India's efforts toward DR-TB control and elimination.