Intensified antibiotic treatment of tuberculosis meningitis

Fiona V. Cresswell, Lindsey Te Brake, Rachel Atherton, Rovina Ruslami, Kelly E. Dooley, Rob Aarnoutse, Reinout Van Crevel

Research output: Contribution to journalReview articlepeer-review


Introduction: Meningitis is the most severe manifestation of tuberculosis, resulting in death or disability in over 50% 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 outcomes. 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 modeling studies to support the use of high-dose rifampicin in TBM, likely to be at least 30 mg/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 the use of molecular pharmacological approaches, physiologically based pharmacokinetic modeling and pharmacokinetic-pharmacodynamic studies to define optimal regimens to be tested in clinical trials. Exciting data from recent studies hold promise for improved regimens and better clinical outcomes in future.

Original languageEnglish (US)
Pages (from-to)267-288
Number of pages22
JournalExpert Review of Clinical Pharmacology
Issue number3
StatePublished - Mar 4 2019


  • TB meningitis
  • Tuberculous meningitis
  • antituberculous therapy
  • intensified

ASJC Scopus subject areas

  • Pharmacology, Toxicology and Pharmaceutics(all)
  • Pharmacology (medical)


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