Incidence, Pattern, Associated Factors and Impact of Peripheral Neuropathy in Patients with Drug-Resistant Tuberculosis Receiving an All-Oral Longer Regimen: A Prospective Observational Study from the Bundelkhand Region of India

Background: Linezolid-associated peripheral neuropathy (PN) commonly leads to treatment modification with all-oral longer regimens for drug-resistant tuberculosis (DR-TB), but prospective programmatic data from India are limited. Aims and Objectives: To determine the incidence, pattern, timing, outcome and impact of PN in DR-TB patients on an all-oral longer regimen and its association with serum vitamin B12 and folic acid. Materials and Methods: In this prospective cohort study at a tertiary centre in Jhansi, 100 adults with DR-TB on an all-oral longer regimen, enrolled in April–May 2025, were followed to 9 months of treatment (completed February 2026); pre-enrolment data were abstracted from programme records. Neuropathy was screened with the Michigan Neuropathy Screening Instrument at treatment initiation and at 3, 6 and 9 months, with nerve conduction confirmation. Associated factors were examined by exploratory logistic regression. Results: PN developed in 19 patients (19%; 95% CI 12.5–27.8), predominantly sensory (78.9%), with onset between 3 and 6 months in 68.4%. On exploratory multivariable analysis, lower serum vitamin B12 was associated with PN (adjusted OR 0.32 per 100 pg/mL, 95% CI 0.18–0.57); folic acid, age and sex were not. Linezolid was dose-reduced in all and discontinued in 68.4%; 52.6% became non-adherent and 89.5% developed anxiety. Twelve (63.2%) recovered clinically by 9 months. Conclusion: One in five DR-TB patients developed PN, mostly sensory and during months 3–6, associated with lower vitamin B12 but not folate, with marked effects on adherence and quality of life. Routine neuropathy screening and nutritional assessment should be integrated into programmatic DR-TB care.