维拉帕米可增加游离/生物膜状态下白色念珠菌对抗真菌药物的敏感性  

Verapamil increases the sensitivity of Candida albicans to antifungal agents in the free/biofilm state

作　　者：冯文莉[1] 杨静[1] 马彦[1] 任乔 赵亚蒙 郝晓瑞 FENG Wen-li;YANG Jing;MA Yan;REN Qiao;ZHAO Ya-meng;HAO Xiao-rui(Department of Dermatovenereology,Second Hospital of Shanxi Medical University,Taiyuan,Shanxi 030001,China)

机构地区：[1]山西医科大学第二医院皮肤性病科,山西太原030001

出　　处：《中国卫生检验杂志》2021年第19期2305-2311,共7页Chinese Journal of Health Laboratory Technology

基　　金：国家自然基金面上项目(82072262);山西省重点研发计划项目(201903D321123);第五批山西省新兴产业领军人才项目(2019);山西省卫生健康委员会科研课题(201601050,2018048)。

摘　　要：目的 探究白色念珠菌在游离状态和生物膜状态下对氟康唑、伊曲康唑、伏立康唑、卡泊芬净联合维拉帕米的体外药物敏感性。方法 采用M27-A4微量肉汤稀释法对39株临床分离白色念珠菌菌株在游离状态以及生物膜状态进行体外药物敏感性试验;利用时间-生长曲线和时间-杀菌曲线实验,探讨维拉帕米与氟康唑联合用药时的最佳抑菌浓度。结果 氟康唑、伊曲康唑、伏立康唑、卡泊芬净与维拉帕米联合用药组的MIC50值低于单一用药组;单一用药组白色念珠菌生物膜状态MIC50值高于游离状态;联合用药组生物膜状态MIC50值高于游离状态;维拉帕米对氟康唑的增敏率达到48. 7%;8μg/ml维拉帕米与氟康唑协同抑菌效果最佳;4μg/ml维拉帕米与8μg/ml氟康唑联用,在12 h即有明显杀菌作用。结论 白色念珠菌在生物膜状态下对抗真菌药物的敏感性低于游离状态;维拉帕米可增加不同状态下白色念珠菌的敏感性,可作为这4种药物的增敏剂。Objective To investigate in vitro drug sensitivity of Candida albicans to fluconazole,itraconazole,voriconazole,carpofungin combining with verapamil in free state and biofilm state.Methods The drug sensitivity test of 39 strains of Candida albicans in vitro was carried out by M27-A4 micro broth dilution method.The optimal inhibitory concentration of verapamil combined with fluconazole was studied by time-growth curve and time-germicidal curve.Results The MIC50 of the combination group of FCA,ITR,VRC,CAS and VPL was higher than that of single group.The MIC50 value of Candida albicans biofilm state in single drug group was higher than that in free state.The MIC50 value of biofilm state in combination group was higher than that in free state.The sensitization rate of verapamil to fluconazole was 48.7%.The synergistic effect of 8 μg/ml verapamil and fluconazole was the best.Combined with 4μg/ml verapamil and 8μg/ml fluconazole,the bactericidal effect was obvious at 12 h.Conclusion The sensitivity of Candida albicans to antifungal drugs in biofilm state was lower than that in free state.Verapamil can increase the sensitivity of Candida albicans in different states and can be used as a sensitizer for all four drugs.

关 键 词：白色念珠菌 生物膜 抗真菌药物 联合用药 药物敏感性 

分 类 号：R446.5[医药卫生—诊断学]