依维莫司单独与联合唑类药物对耐药念珠菌体外敏感研究  

In vitro susceptibility study of drug-resistant Candida species to everolimus alone and combined with azoles

作　　者：胡静[1] 李珑婷 孙毅[1] 李娟[3] HU Jing;LI Longting;SUN Yi;LI Juan(Department of Dermatology and Venereology,Jingzhou Hospital Affiliated to Yangtze University,Jingzhou Central Hospital,Jingzhou,Hubei 434100,China;Department of Reproductive Medicine,Jingzhou Hospital Affiliated to Yangtze University,Jingzhou Central Hospital,Jingzhou,Hubei 434100,China;Department of General Medicine,Jingzhou Hospital Affiliated to Yangtze University,Jingzhou Central Hospital,Jingzhou,Hubei 434100,China)

机构地区：[1]长江大学附属荆州医院、荆州市中心医院皮肤病与性病科,湖北荆州434100 [2]长江大学附属荆州医院、荆州市中心医院生殖医学科,湖北荆州434100 [3]长江大学附属荆州医院、荆州市中心医院全科医学科,湖北荆州434100

出　　处：《安徽医药》2024年第6期1116-1120,共5页Anhui Medical and Pharmaceutical Journal

基　　金：湖北省自然科学基金项目(2019CFB567);湖北省卫生健康委科研项目(WJ2021M261)。

摘　　要：目的探讨依维莫司单独及联合伊曲康唑、伏立康唑、泊沙康唑和氟康唑对耐药念珠菌及耳念珠菌的体外作用。方法于2022年3—6月,采用美国临床实验室标准研究所M27-A3微量稀释法和微量肉汤稀释棋盘技术研究依维莫司联合伊曲康唑、伏立康唑、泊沙康唑及氟康唑对耐药念珠菌及耳念珠菌的体外治疗作用。通过测定最低抑菌浓度(MIC)和部分抑菌浓度指数来确定协同效应。结果依维莫司单药治疗22株耐药念珠菌及10株耳念珠菌的MIC为0.250~4.000 mg/L、1.000 mg/L,伊曲康唑、伏立康唑、泊沙康唑、氟康唑单独使用对22株耐药念珠菌MIC范围分别为0.125~4.000 mg/L、<0.125~2.000 mg/L、0.063~2.000 mg/L、1.000~64.000 mg/L,伊曲康唑、伏立康唑、泊沙康唑单独使用对10株耳念珠菌MIC范围分别为0.500~2.000 mg/L、0.125~8.000 mg/L、0.125~1.000 mg/L。当依维莫司与伊曲康唑、伏立康唑、泊沙康唑、氟康唑联合使用时,对耐药念珠菌的协同作用分别是9株(40.90%)、4株(18.18%)、8株(36.36%)、9株(40.90%)。当依维莫司联合唑类作用于耳念珠菌,未发现任何拮抗作用。结论依维莫司单独使用对耐药念珠菌及耳念珠菌菌株具有明显抗真菌作用,同时依维莫司联合唑类作用于耐药念珠菌时,表现出良好的协同作用,且没有拮抗作用,其进一步提升其抗耐药念珠及耳念珠菌的作用。Objective To investigate the in vitro effects of everolimus alone and in combination with itraconazole,voriconazole,posaconazole and fluconazole on drug-resistant Candida and Candida auris.Methods From March to June 2022,the American Institute for Clinical Laboratory Standards M27-A3 microdilution method and the microbroth dilution checkerboard technique were used.Everolimus in combination with itraconazole,voriconazole,posaconazole and fluconazole was used for the in vitro treatment of drug-resistant Candida and C.auris.The synergistic effects were determined by measuring the minimum inhibitory concentration(MIC)and partial inhibitory concentration index.Results The MICs of everolimus monotherapy for 22 strains of drug-resistant Candida and 10 strains of C.auris ranged from 0.250 to 4.000 mg/L and 1.000 mg/L,respectively.The MICs of itraconazole,voriconazole,posaconazole,and fluconazole alone for 22 strains of drug-resistant Candida ranged from 0.125 to 4.000 mg/L,<0.125 to 2.000 mg/L,0.063 to 2.000 mg/L,and 1.000 to 64.000 mg/L,respectively.The MICs of itraconazole,voriconazole,posaconazole alone for 10 strains of C.auris ranged from 0.500 to 2.000 mg/L,0.125 to 8.000 mg/L,and 0.125 to 1.000 mg/L,respectively.When everolimus was combined with itraconazole,voriconazole,posaconazole,or fluconazole,synergistic effects on 9(40.90%),4(18.18%),8(36.36%),and 9(40.90%)drug-resistant Candida strains were detected,respectively.When everolimus was combined with azoles to treat C.auris,no antagonistic effects were detected.Conclusion Everolimus alone had significant antifungal effects on drug-resistant Candida and C.auris strains,while everolimus combined with azoles showed good synergism and no antagonistic effects on drug-resistant Candida strains,which further enhanced its effects on drug-resistant Candida and C.auris strains.

关 键 词：念珠菌病 抗药性 真菌 依维莫司 耐药念珠菌 耳念珠菌 体外研究 M27-A3微量稀释法 

分 类 号：R446.5[医药卫生—诊断学]