Effect of thioridazine on experimental cutaneous staphylococcal infections.

BACKGROUND Some non-antibiotic drugs, such as the phenothiazine antipsychotic agents, may have antimicrobial activity. MATERIALS AND METHODS We sought to determine the in vivo antimicrobial effects of the phenothiazine thioridazine in two mouse models of Staphylococcus aureus skin infection. RESULTS Thioridazine significantly suppressed dissemination from skin to spleen and kidney after inoculation of the skin surface. However, the drug did not affect infection parameters in the skin itself. Thioridazine did suppress the size of abscesses produced when the bacteria were injected intradermally. On the other hand, using the cutaneous abscess model we were not able to demonstrate synergistic activity between thioridazine and the β-lactam drug cefazolin against methicillin-resistant S. aureus, as previously demonstrated in vitro. CONCLUSION The phenothiazine drug thioridazine has in vivo antimicrobial activity against certain S. aureus skin infections, although the previously-demonstrated reversal of methicillin resistance by this agent may not be readily evident in vivo.