BACKGROUND

Meningitis is the most severe manifestation of tuberculosis, resulting in death or disability in over 30% of those affected, with even higher morbidity and mortality among patients with HIV or drug resistance. Antimicrobial treatment of Tuberculous meningitis (TBM) is similar to treatment of pulmonary tuberculosis, although some drugs show poor central nervous system penetration. Therefore, intensification of antibiotic treatment may improve TBM treatment outcome. Areas covered: In this review we address three main areas: available data for old and new anti-tuberculous agents; intensified treatment in specific patient groups like HIV co-infection, drug-resistance and children; and optimal research strategies. Expert commentary: There is good evidence from preclinical, clinical and modelling studies to support use of high-dose rifampicin in TBM, likely to be at least 30mg/kg. Higher dose isoniazid could be beneficial, especially in rapid acetylators. The role of other first and second line drugs is unclear, but observational data suggest that linezolid, which has good brain penetration, may be beneficial. We advocate use of molecular pharmacological approaches, physiologically-based pharmacokinetic (PBPK) modelling and pharmacokinetic-pharmacodynamic (PK-PD) studies to define optimal regimens to be tested in clinical trials. Fortunately, exciting data from recent studies hold promise for improved regimens and better outcome of TBM patients.