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Beyond Rifampin: Evaluating Rifapentine and Rifabutin as Alternative Treatments for Tuberculous Meningitis
Xueyi Chen1,2, Carlos E Ruiz-Gonzalez3,4, Yuderleys Masias-Leon3,4
1Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
The Journal of Infectious Diseases
|February 10, 2026
Summary
New rifamycin drugs, rifapentine and rifabutin, show promise for treating tuberculous meningitis (TB meningitis). These alternatives demonstrated brain bactericidal activity and reduced neuroinflammation and injury in mice, suggesting potential for clinical trials.
Area of Science:
- Infectious Diseases
- Neurology
- Pharmacology
Background:
- Tuberculous meningitis (TB meningitis) is a severe form of tuberculosis with high mortality and neurological damage.
- Current rifampin regimens have limited efficacy in the central nervous system.
- Rifapentine and rifabutin are alternative rifamycins with different pharmacokinetic profiles, showing efficacy in pulmonary TB.
Purpose of the Study:
- To evaluate the efficacy of rifapentine- and rifabutin-based regimens in a mouse model of tuberculous meningitis.
- To assess the neuroprotective effects of these alternative rifamycins.
Main Methods:
- Mice were intracranially inoculated with Mycobacterium tuberculosis.
- Treatment involved rifamycin (rifampin, rifapentine, or rifabutin)-based regimens at human equipotent doses.
- Assessed bactericidal activity, tissue concentrations, neuroinflammation (MRI, immunofluorescence, cytokines), and neuronal injury.
Main Results:
- Rifapentine- and rifabutin-containing regimens showed comparable or superior brain bactericidal activity to rifampin.
- These alternative regimens significantly reduced neuroinflammation and brain injury.
- Both drugs demonstrated therapeutic activity and neuroprotective effects.
Conclusions:
- Rifapentine and rifabutin show therapeutic potential for tuberculous meningitis.
- Their neuroprotective effects support further investigation in clinical trials.
- These findings may lead to improved treatment strategies for TB meningitis.
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