桂皮醛联合伏立康唑对临床分离烟曲霉菌的体外作用研究

摘要

目的：评价桂皮醛与伏立康唑（VRC）联合应用对临床分离烟曲霉菌的体外抗菌活性。方法参照美国临床和实验室标准协会（CLSI）推荐的微量液基稀释法及棋盘法，分别测定桂皮醛、VRC单独使用及联合使用对42株临床分离烟曲霉菌的最小抑菌浓度（MIC），比较2药单用与联用的MIC50、MIC90、MIC几何均数（MICG）及MIC分布；绘制浓度-累积抑菌百分率曲线并计算分级抑菌指数（FICI），判断药物联合作用的类型。结果桂皮醛与VRC联用后，2药的MIC50、MIC90及MICG均较各自单用时明显降低（P＜0.01），MIC峰值分布及浓度-累积抑菌百分率曲线较单用时左移；2药联用的FICI值为0.1875~1.5，其中16株（38.10%）体现为协同作用，19株（45.23%）为相加作用，7株（16.67%）为无关作用，未出现拮抗作用。受试菌株对VRC的敏感性越低，2药联用的FICI均数越小。结论桂皮醛与VRC联用对临床分离烟曲霉菌的体外联合抗菌效应主要表现为协同和相加作用，且该药物组合对VRC敏感性较低的烟曲霉菌表现出较强的协同抗菌作用。%Objective To evaluate the in vitro antifungal activity of Cinnamaldehyde in combination with Voriconazole (VRC) against clinically isolated Aspergillus fumigatus strains. Methods According to the Clinical and Laboratory Stan⁃dards Institute (CLSI) M38-A2 document,the minimal inhibitory concentrations (MIC) of Cinnamaldehyde and VRC alone or in combination against 42 clinical Aspergillus fumigatus isolates were determined by both microdillution method and check⁃board method respectively. The MIC50, MIC90, MICG and MICs distribution were compared between single drug and both in combination. The concentration-accumulative curve was drawn and fractional inhibitory concentration index (FICI) was cal⁃culated to evaluate the interaction between two test agents. Results The values of MIC50, MIC90 and MICG were significant⁃ly decreased (P<0.001) when combination of the two drugs than those of their single use, with their MIC distribution concen⁃tration-accumulative curves shifted to the left. The value of FICI of Cinnamaldehye-VRC combination ranged from 0.187 5 to 1.5. Sixteen strains (38.10%) of them showed the synergistic effect, 19 strains (45.23%) showed additive effect, and 7 strains (16.67%) showed an unrelated effect, and no antagonist effect on tested Aspergillus fumigatus strains in vitro. Conclu⁃sion Cinnamaldehye in combination with VRC mainly shows a combined synergic and additive inhibitory effect on Asper⁃gillus fumigatus isolates, and this combination appears to be more active against the test strains, which are less susceptible to voriconazole.