Treatment of Tuberculous Meningitis and Its Complications in Adults

Tuberculous meningitis (TBM) is a global health problem. In this review, we systematically evaluate the evidence for current and emerging antimicrobials, host-directed therapies and supportive managements.

Current antimicrobial regimes do not factor the differing ability of drugs to cross the blood-brain barrier. Rifampicin may be more effective at higher doses yet the most recent clinical trial failed to demonstrate survival benefit at 15 mg/kg/day. Dose finding studies suggest that higher doses still may be safe and more effective. Fluoroquinolones are currently listed as important second-line agents in drug-resistant TBM; however, a survival benefit as a first-line agent has yet to be shown. Linezolid may be a promising antimicrobial with good central nervous system penetrance. Dexamethasone reduces mortality in HIV-uninfected individuals yet evidence for its use in HIV co-infection is lacking. Aspirin has anti-inflammatory and anti-thrombotic properties. Small studies have demonstrated efficacy in reducing stroke but further research is required to better understand its effect on controlling the host inflammatory response. Discovery of genetic polymorphisms may direct individualized immune therapies and mediators of the innate immune response may provide targets for the development of novel therapies. There is at present no significant evidence base to guide management of hydrocephalus in HIV co-infection. Further clinical trial data is required to improve treatment outcomes in TBM in particularly in regard to the value of high-dose rifampicin, newer antimicrobials with improved central nervous system penetration and host-directed therapies. Supportive measures in particular the management of hydrocephalus in HIV co-infection should be an area for future research.