In vitro and in vivo antimicrobial activity of pimozide against Staphylococcus aureus

Abstract:

Objective To explore the in vitro and in vivo antimicrobial activity of antipsychotic agent pimozide against Staphylococcus aureus (S. aureu). Methods The minimal inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of pimozide were determined by micro-dilution assay. Biofilm was cultured in 96-well cell culture plate, and the anti-biofilm activity of pimozide was detected by turbidimetry. The effect of pimozide on biofilm was further observed through laser confocal microscopy and SYTO9/PI staining. Combined antimicrobial effect of pimozide and other antimicrobial agents was detected by chessboard dilution method, and cytotoxicity of pimozide was detected by CCK-8 assay kit. A model of skin abscess was constructed, in vivo antimicrobial activity and toxicity of pimozide was tested. Results Pimozide showed significant dose-dependent antimicrobial activity against S. aureu, with a MIC of 8-16 μg/mL. It could significantly inhibit the formation of S. aureu biofilm and disperse the formed biofilm. The combination of pimozide and doxycycline has a synergistic antimicrobial effect in vitro, with a synergistic antimicrobial index of 0.5. It can significantly reduce the bacterial load in mouse abscess tissue in vivo, and reduce the live bacterial count from (8.25±0.13) lgarithmic value of CFU/abscess to (3.31±0.81) logarithmic value of CFU/abscess (q=3.74, P < 0.05). The cytotoxicity of pimozide was extremely low, with a half inhibitory concentration of 64 μg/mL on cells. Conclusion Pimozide exhibits significant antimicrobial activity in vitro and in vivo with extremely low toxicity, thus is promising for the treatment of S. aureu-related local infection in psychiatric patients.