匹莫齐特对金黄色葡萄球菌的体外和体内抗菌研究  

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

作　　者：陈体[1] 段瑶 张晓洁[2,3] 佘鹏飞 李颖佳 CHEN Ti;DUAN Yao;ZHANG Xiao-jie;SHE Peng-fei;LI Ying-jia(Department of Laboratory Medicine,The Third Xiangya Hospital of Central South University,Changsha 410013,China;Department of Psychiatry,The Second Xiangya Hospital of Central South University,Changsha 410011,China;National Clinic Research Center for Mental Disorders,Changsha 410011,China)

机构地区：[1]中南大学湘雅三医院检验科,湖南长沙410013 [2]中南大学湘雅二医院精神卫生研究所,湖南长沙410011 [3]国家精神心理疾病临床医学研究中心,湖南长沙410011

出　　处：《中国感染控制杂志》2023年第12期1475-1482,共8页Chinese Journal of Infection Control

基　　金：湖南省自然科学基金项目(2021JJ40944)。

摘　　要：目的探讨抗精神病类药物匹莫齐特对金黄色葡萄球菌的体外和体内抗菌活性。方法采用微量肉汤稀释法检测匹莫齐特的最低抑菌浓度(MIC)和最低杀菌浓度(MBC)。通过96孔细胞培养板构建生物膜,利用比浊法检测匹莫齐特的抗生物膜活性,进一步通过激光共聚焦显微镜和SYTO9/PI染色观察匹莫齐特对生物膜的作用。采用棋盘稀释法检测匹莫齐特与抗菌药物联合抗菌效果,CCK-8试剂盒检测匹莫齐特的细胞毒性。构建皮肤脓肿模型,检测匹莫齐特的体内抗菌活性及毒性。结果匹莫齐特对金黄色葡萄球菌具有明显的剂量依赖抑菌活性,其MIC为8~16μg/mL,能显著抑制金黄色葡萄球菌生物膜的形成并分散已形成的生物膜。匹莫齐特与多西环素联合,体外具有协同抗菌效果,其协同抑菌指数为0.5;体内能显著降低小鼠脓肿组织中的细菌载量,使活菌量从(8.25±0.13)对数值CFU/脓肿减少到(3.31±0.81)对数值CFU/脓肿(q=3.74,P<0.05);匹莫齐特的细胞毒性极低,对细胞的半数抑制浓度>64μg/mL。结论匹莫齐特毒性低且具有明显的体外和体内抗菌活性,有望成为一种精神病患者合并局部金黄色葡萄球菌相关感染的治疗药物。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 8-16μg/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 64μg/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.

关 键 词：匹莫齐特 金黄色葡萄球菌 抗菌作用 生物膜 联合药敏试验 

分 类 号：R978.1[医药卫生—药品]