Addition of Clofazimine Enhances the Activity of Standard Treatment Regimen in a Mouse Model of Tuberculous Meningitis

Abstract Tuberculous meningitis causes substantial mortality due to limited penetration of antibiotics to the central nervous system and excessive neuroinflammation. This study evaluated clofazimine as an adjunct to the standard first-line tuberculosis regimen, in a mouse model. Mice were infected intracerebrally with Mycobacterium tuberculosis and treated for six weeks. Addition of clofazimine markedly reduced the brain bacterial burden, achieving measurable brain tissue concentrations despite minimal cerebrospinal fluid penetration, as well as attenuated brain tissue inflammation. These findings indicate that clofazimine enhances bactericidal activity of the standard regimen and mitigate neuroinflammation, supporting further investigation and clinical evaluation for tuberculous meningitis.