The synergy of honokiol and fluconazole against clinical isolates of azole-resistant Candida albicans

The synergy of honokiol and fluconazole against clinical isolates of azole-resistant Candida albicans
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DOI:
10.1111/j.1472-765x.2010.02900.x
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发表时间:
2010-09-01
影响因子:
2.4
通讯作者:
Yu, L.
Yu, L.
中科院分区:
生物学4区
文献类型:
--
作者:
Jin, J.;Guo, N.;Yu, L.

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目的:评价氟康唑(FLC)和宏木酚(HNK)在体外和体内对临床分离的耐唑白色念珠菌(azole-R)的相互作用。方法与结果:采用棋盘格微量稀释法对24株azole-R型临床分离的白色念珠菌进行FLC与HNK的体外相互作用研究。体内抗真菌活性进一步分析FLC和HNK的相互作用。在体外研究中,通过分数抑制浓度指数(FICI)测定的所有24株flc耐药菌株和通过delta E模型测定的22株菌株均观察到协同作用。在所有测试菌株中均未观察到拮抗活性。选用的白色念珠菌YL371对HNK和FLC的联合敏感,时间杀伤试验也证实了这种正相互作用。在体内研究中,通过HNK与FLC联合治疗,成功治疗了念珠菌病小鼠,结果显示,在本研究使用的治疗条件下,感染和治疗动物的菌落形成单位比对照组减少。结论:在体外和体内观察到HNK和FLC对临床分离株FLC耐药白色念珠菌的协同作用。研究的意义和影响:本报告可能为克服白色念珠菌的耐药问题提供一种潜在的治疗方法。
Aims:To evaluate the interaction of fluconazole (FLC) and honokiol (HNK) in vitro and vivo against azole-resistant (azole-R) clinical isolates of Candida albicans.Methods and Results:A checkerboard microdilution method was used to study the in vitro interaction of FLC and HNK in 24 azole-R clinical isolates of C. albicans. In vivo antifungal activity was performed to further analyse the interaction between FLC and HNK. In the in vitro study, synergism was observed in all 24 FLC-resistant strains tested as determined by fractional inhibitory concentration index (FICI), and in 22 strains by delta E models. No antagonistic activity was observed in any of the strains tested. These positive interactions were also confirmed by using the time-killing test for the selected strain C. albicans YL371, which shows strong susceptible to the combination of HNK and FLC. In the in vivo study, the mice with candidiasis were treated successfully by a combination therapy of HNK with FLC, the results showed a decrease of the colony forming unit in infected and treated animals compared to the controls, at the conditions of the treatment used in this study.Conclusions:Synergistic activity of HNK and FLC against clinical isolates of FLC-resistant C. albicans was observed in vitro and in vivo.Significance and Impact of the Study:This report might provide a potential therapeutic method to overcome the problem of drug-resistance in C. albicans.