Optimizing Pyrazinamide Use: A Low-Hanging Fruit in Improving Outcomes with Tuberculous Meningitis? Narrative Review.

Tuberculous meningitis (TBM) disables more than a third of its sufferers. Recent research has focused on optimizing the antitubercular regimen, mainly by increasing the dosage of rifampicin. However, pyrazinamide, with higher penetration into the central nervous system, is generally overlooked. We discuss the potential clinical impact of using pyrazinamide throughout antitubercular therapy in TBM, in contrast to only the intensive phase. This approach may improve the treatment outcomes and reduce disability in TBM. We summarize the available data regarding this approach from in vitro studies, clinical cohorts, toxicity data, and baseline resistance rates. Additionally, we discuss the two ongoing clinical trials evaluating this approach.