以棋盘法测定汉防己甲素联合伏立康唑的体外抗烟曲霉活性

【摘要】 目的 探讨汉防己甲素对伏立康唑抗烟曲霉的体外增效活性。 方法 参照美国临床和实验室标准协会（CLSI）推荐的M38-A2方案，采用棋盘式微量液基稀释法测定汉防己甲素联合伏立康唑对21株烟曲霉临床株的抗真菌活性，以吸光度A值测定法判读最低抑菌浓度，并以FICI法评价联合用药的效果，同时以其中的CMCC（F）A.1a株为代表，用等效线图解法验证结果。 结果 汉防己甲素与伏立康唑单独作用于上述烟曲霉临床株的最低抑菌浓度分别为512 μg/ml和0.125 ~ 2 μg/ml，联合用药时的最低抑菌浓度值分别降至8 ~ 128 μg/ml和0.03 ~ 0.5 μg/ml，且终点清晰，“拖尾现象”消失，FICI值为0.13 ~ 0.63，有16株菌表现为协同作用，其余菌株表现为无关作用。CMCC株相应的MIC值等效曲线是凹形，也表明具有协同作用。 结论 汉防己甲素对伏立康唑抗烟曲霉有体外增效活性。

In vitro evaluation of the activity of tetrandrine combined with voriconazole against Aspergillus fumigatus by a checkerboard method

Diao Wenqi *, Wu Rui, Song Yanjun, Li Shuixiu, Lyu Xialin, Wang Luxia, Liu Weida, Zhang Hong. *Department of Dermatology, First Affiliated Hospital; Institute of Mycology, Jinan University, Guangzhou 510632, ChinaCorresponding author: Zhang Hong, Email: tzhangh@jnu.edu.cn 【Abstract】 Objective To evaluate the synergistic effect of tetrandrine （TET） with voriconazole （VRC）against Aspergillus fumigatus. Methods A checkerboard microdilution method was used to estimate the activity of TET combined with VRC against 21 clinical isolates of Aspergillus fumigatus according to the Clinical and Laboratory Standards Institute （CLSI） M38-A2 document. The minimal inhibitory concentration （MIC） was determined using spectrophotometry. Fractional inhibitory concentration index （FICI） was calculated to evaluate the interaction between the two antifungal agents. The isobologram method was used to verify the test results with the Aspergillus fumigatus strain CMCC （F） A.1a as the representative strain. Results The MICs of TET and VRC against these clinical isolates were 512 μg/ml and 0.125 － 2 μg/ml, respectively when used alone, 8 － 128 μg/ml and 0.03 － 0.5 μg/ml respectively with clear end points accompanied by disappearance of the so-called "trailing" phenomenon when used in combination. The FICI of these agents ranged from 0.13 to 0.63. The interaction between TET and VRC was synergistic in 16 clinical isolates, but indifferent in the remaining strains. Moreover, the isobologram analysis revealed concaves with a shape characteristic of synergy. Conclusion TET exerts a synergistic effect with VRC against Aspergillus fumigatus.