Abstract: 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, China Corresponding 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.

Key words: Tetrandrine, Voriconazoles, Aspergillus fumigates, Synergistic effect, Checkerboard microdilution method