Two phenothiazines to treat meningitis

INDICATION: Meningitis

Cell culture and mouse studies identified two phenothiazine-based compounds that could help treat meningitis caused by Neisseria meningitides. In cultures of primary human endothelial cells isolated from dermal microvessels and colonized with N. meningitides, the phenothiazine-based compounds trifluoperazine and thioridazine decreased endothelial cell junction and basement membrane injuries, which are markers of disease, compared with no treatment. In a mouse model of meningococcal infection, trifluoperazine or thioridazine decreased bacterial colonization of human blood vessels and serum levels of inflammatory cytokines compared with vehicle. Also in the model, trifluoperazine decreased bacteremia and increased survival, and trifluoperazine in combination with the cephalosporin antibiotic cefotaxime decreased serum levels of inflammatory cytokines compared with cefotaxime alone. Next steps could include testing trifluoperazine and thioridazine in other models of meningitis and identifying the compounds' target...