In vitro and in vivo antimicrobial activity of pimozide against Staphylo-coccus aureus
10.12138/j.issn.1671-9638.20234213
- VernacularTitle:匹莫齐特对金黄色葡萄球菌的体外和体内抗菌研究
- Author:
Ti CHEN
1
;
Yao DUAN
;
Xiao-Jie ZHANG
;
Peng-Fei SHE
;
Ying-Jia LI
Author Information
1. 中南大学湘雅三医院检验科,湖南长沙 410013
- Keywords:
pimozide;
Staphylococcus aureus;
antimicrobial action;
biofilm;
combined antimicrobial susceptibility testing
- From:
Chinese Journal of Infection Control
2023;22(12):1475-1482
- CountryChina
- Language:Chinese
-
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.