Tuberculous meningitis: a comprehensive review of pathogenesis, clinical features and therapeutic strategies

Abstract

Tuberculous meningitis (TBM) is the most severe form of tuberculosis affecting the central nervous system, associated with high mortality and long-term neurological disability. Diagnostic delays, limited drug penetration into the cerebrospinal fluid, and emerging drug resistance continue to complicate effective management.
This review aims to summarize current evidence (2020–2025) regarding therapeutic strategies for TBM, including standard antituberculosis therapy, optimized rifampin dosing, carbapenem use, fluoroquinolones, linezolid, corticosteroids, and aspirin as an adjunct treatment. Special emphasis is placed on drug-resistant TBM and pharmacokinetic considerations. A narrative review was conducted using articles published between 2020 and 2025 from PubMed, Scopus, Web of Science, and institutional sources. Key search terms included “tuberculous meningitis,” “CNS tuberculosis,” “rifampin pharmacokinetics,” “drug-resistant TBM,” “carbapenems,” “fluoroquinolones,” “linezolid,” and “adjunctive therapies.” Recent evidence supports the use of higher-dose rifampin to enhance central nervous system penetration. Carbapenems (meropenem and imipenem) and linezolid have shown clinical benefit, particularly in drug-resistant TBM. Moxifloxacin and levofloxacin offer additional therapeutic roles. Corticosteroids remain beneficial in reducing mortality in HIV-negative patients, while aspirin may reduce stroke risk and modulate inflammation. However, despite therapeutic advances, outcomes in multidrug-resistant TBM remain poor. Therapeutic advances, including optimized drug dosing and promising adjunctive agents, have improved TBM management. Nonetheless, early diagnosis, individualized pharmacologic approaches, and better strategies for drug-resistant disease remain critical priorities to reduce mortality and improve neurological outcomes.