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Review
. 2025 Feb;14(2):317-325.
doi: 10.1007/s40121-024-01102-1. Epub 2025 Jan 3.

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

Bella Devaleenal Daniel #  1 , Leeberk Raja Inbaraj #  2 , Shanmugapriya Kumaravadivelu  2 , Kathirvel Subramanian  2 , Balaji Ramraj  2 , Abi Manesh  3
Affiliations
Review

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

Bella Devaleenal Daniel et al. Infect Dis Ther. 2025 Feb.

Abstract

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.

Keywords: Duration; Pyrazinamide; Treatment; Tuberculous meningitis.

Plain language summary

Tuberculosis (TB) is a disease caused by the organism Mycobacterium tuberculosis. TB meningitis (TBM) is a medical condition in which the layers covering the brain are infected with TB bacteria. TBM is one of the worst forms of TB as it kills a lot of people who suffer with the disease and leaves many permanently disabled. Currently, the World Health Organization recommends 12 months of treatment for TBM. The drugs used in the treatment are rifampicin, isoniazid, ethambutol, and pyrazinamide. Usually, pyrazinamide is given only for the first 2 months of TB treatment. Many studies have shown that pyrazinamide penetrates the brain better than other drugs and kills TB bacteria more effectively. In addition, ethambutol does not get into the brain well compared to other drugs. In this narrative review, we present evidence to reconsider the duration of pyrazinamide usage beyond 2 months for improving the results of TBM treatment. We also report the challenges of this approach, such as side effects and pyrazinamide resistance.

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Conflict of interest statement

Declarations. Conflict of Interest: The authors (Bella Devaleenal Daniel, Leeberk Raja Inbaraj, Shanmugapriya Kumaravadivelu, Kathirvel Subramanian, Balaji Ramraj, Abi Manesh) declare that they do not have any conflicts of interest. Ethical Approval: This article is based on previously conducted studies and does not contain any new studies with human participants or animals performed by any of the authors.

References

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