An update on recent developments in the drug treatment of tuberculous meningitis

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Abstract

INTRODUCTION: Tuberculous Meningitis (TBM) is an often lethal form of tuberculosis with damage to the brain resulting from a combination of direct effects from the causative pathogen M. tuberculosis and from the host inflammatory response. Cerebral infarction is frequent. Those who do survive often suffer severe neurological disability. The treatment regimen for TBM comprises 4 antitubercular drugs and anti-inflammatory glucocorticoids. The regimen has not changed for over 40 years. AREAS COVERED: In this review we summarize recent clinical trials, supported by human pharmacokinetic studies and animal disease models, that have attempted to improve the current regimen for TBM, and highlight major trials due to report soon. A literature search of the National Library of Medicine (PubMed) July 2019- October 2025 inclusive was performed to inform this update. EXPERT OPINION: Efforts to intensify the antitubercular therapy arm (ATT) of TBM treatment have not yet demonstrated improvement in clinical outcomes, However there are large trials soon to report. It may be that to improve survival in TBM, it is not enhanced bacterial killing that is needed, but better modulation of the neuroinflammatory response of the host. Better understanding of the inflammatory mechanisms must be sought, to allow specific targeting of deleterious immune pathways.