Drug resistance in tuberculous meningitis: A laboratory-based observational study from Northern India's tertiary care referral centre.

Tuberculous meningitis (TBM) is the most severe form of tuberculosis and is associated with high mortality and long-term neurological disability. Detection of drug resistance remains challenging because cerebrospinal fluid (CSF) specimens are typically paucibacillary and often available only in limited volumes. This retrospective laboratory based study characterized drug-resistance patterns and diagnostic attrition across the laboratory testing cascade using CSF samples from patients with presumed TBM referred between January 2023 and December 2025 in a high tuberculosis-burden setting. Samples underwent Mycobacterium tuberculosis cartridge-based nucleic acid amplification testing (CBNAAT), automated liquid culture, line probe assays and phenotypic drug susceptibility testing according to national guidelines. Of 8926 CSF samples tested by CBNAAT, 812 (9.0%) were positive for M. tuberculosis. Rifampicin resistance was detected in 17.0% (138/812; 95% CI: 14.6-19.7) of positive cases. Only 837 samples had sufficient volume for culture, of which 58 (6.9%; 95% CI: 5.4-8.9) were culture-positive. Among these isolates, 29 (50.0%; 95% CI: 37.5-62.5) were multidrug resistant (MDR-TB). Six MDR isolates were also fluoroquinolone resistant, including one extensively drug-resistant (XDR-TB) isolate. These findings demonstrate a high burden of drug resistance, substantial diagnostic attrition, and the need to expand access to comprehensive drug-susceptibility testing in TBM.