土槿皮乙酸与氟康唑联合应用于体外抗白念珠菌活性研究  

Activity of pseudolaric acid B combined with fluconazole against Candida albican in vitro

作　　者：李贞 殷红梅[1] 陈伟琴[1] 薛赢俊 胡骏[1] 诸斌 胡晓波[1] LI Zhen;YIN Hongmei;CHEN Weiqin;XUE Yingjun;HU Jun;ZHU Bin;HU Xiaobo(Department of Clinical Laboratory,Longhua Hospital,Shanghai University of Traditional Chinese Medicine,Shanghai 200032,China)

机构地区：[1]上海中医药大学附属龙华医院检验科,上海200032

出　　处：《检验医学》2020年第7期663-667,共5页Laboratory Medicine

基　　金：上海中医药大学附属龙华医院国家中医临床研究基地龙医学者育苗计划资助项目(LYTD-66)。

摘　　要：目的探讨土槿皮乙酸(PAB)联合氟康唑对白念珠菌的抑菌效果,为临床抗真菌治疗提供依据。方法收集氟康唑耐药及敏感白念珠菌临床分离株33株,分别采用微量稀释法及棋盘式微量稀释法测定PAB单独及与氟康唑联用时的最小抑菌浓度(MIC),以部分抑菌浓度指数(FICI)评估联用时药物体外相互作用的方式,采用时间-杀菌曲线试验动态监测2种药物体外联用的效果。结果 PAB单独作用时,对氟康唑耐药及敏感白念珠菌有类似的抑菌效果,MIC为4-32μg/mL。PAB与氟康唑联用可增加耐药白念珠菌对药物的敏感性(氟康唑MIC由≥128μg/mL降至≤16μg/mL,PAB MIC降至≤2μg/mL)。对氟康唑耐药的12株白念珠菌均表现出协同抑菌的效果(FICI为0.035-0.188);对氟康唑敏感的21株菌株中,10株(47.62%)有协同抑菌效果(FICI范围为0.188-0.375),11株无相互作用(FICI>0.5)。结论 PAB可抑制白念珠菌的生长,与氟康唑联用还有较好的协同抑菌效果,尤其对耐氟康唑白念珠菌,抑菌效果更好。Objective To evaluate the activity of pseudolaric acid B(PAB) combined with fluconazole against Candida albican in vitro,and to provide a reference for antifungal treatment. Methods Totally,33 isolates of fluconazole-susceptible and fluconazole-resistant Candida albican were collected. The minimum inhibitory concentrations(MIC) of PAB alone and in combination with fluconazole against Candida albican were determined by microdilution method and chequerboard microdilution method,respectively. The drug interactions were analyzed by fractional inhibitory concentration index(FICI). Time-kill curves were used to monitor dynamically the antifungal activity of PAB combined with fluconazole. Results When PAB used alone,it had similar antifungal effect on fluconazole-susceptible and fluconazole-resistant Candida albican with MIC 4-32 μg/mL. The combination of PAB and fluconazole increased the drug susceptibility of drug-resistant Candida albican. The MIC of fluconazole was decreased from ≥128 μg/mL to ≤16 μg/mL,and the MIC of PAB was decreased to ≤2 μg/mL. Synergism was observed in all 12 isolates of fluconazole-resistant Candida albican with FICI 0.035-0.188,10(47.62%) isolates of fluconazolesusceptible Candida albican showed synergistic effect(FICI 0.188-0.375),and the other 11 isolates of fluconazolesusceptible Candida albican displayed no interaction. Conclusions PAB can inhibit the growth of Candida albican,and shows synergistic effect when used in combination with fluconazole,especially for fluconazole-resistant Candida albican.

关 键 词：土槿皮乙酸 白念珠菌 氟康唑 耐药 

分 类 号：R446.1[医药卫生—诊断学]