青蒿素类联合抗真菌药对阿萨希毛孢子菌的体外作用  

In vitro interaction of artemisinins combined with antifungal agents against Trichosporon asahii

作　　者：骆万婷 杨鑫 李海涛[2] 杨蓉娅[1,2] LUO Wan-ting;YANG Xin;LI Hai-tao;YANG Rong-ya(The Second School of Clinical Medicine,Southern Medical University,Guangzhou,Guangdong 510515,China;不详)

机构地区：[1]南方医科大学第二临床医学院皮肤科,广东广州510515 [2]解放军总医院第七医学中心皮肤科,北京100700

出　　处：《中华医院感染学杂志》2022年第9期1281-1285,共5页Chinese Journal of Nosocomiology

基　　金：国家自然科学基金资助项目(81571972、81472892)。

摘　　要：目的 评估青蒿素及其衍生物单药及联合常用抗真菌药对阿萨希毛孢子菌(T.asahii)浮游状态及生物膜状态下的体外抑菌效果。方法 以15株T.asahii临床株为研究对象,采用微量肉汤稀释法测定青蒿素、双氢青蒿素、青蒿琥酯对T.asahii浮游菌的最低抑菌浓度(MIC),并测定最敏感青蒿素类药物联合5种抗真菌药(氟康唑、咪康唑、伊曲康唑、两性霉素B、卡泊芬净)对T.asahii浮游菌及生物膜的体外抑制作用,计算部分抑菌浓度指数(FICI)。结果 相比于青蒿素、双氢青蒿素,T.asahii对青蒿琥酯的敏感性最高。青蒿琥酯与卡泊芬净、青蒿琥酯与咪康唑、青蒿琥酯与氟康唑联用对T.asahii浮游菌均具有协同作用,比例分别为73.3%、33.3%、33.3%,青蒿琥酯与卡泊芬净、青蒿琥酯与咪康唑、青蒿琥酯与两性霉素、青蒿琥酯与氟康唑联用对T.asahii生物膜也具有不同程度的协同作用,比例分别为66.7%、53.3%、33.3%、26.7%。结论 青蒿琥酯单药对T.asahii的体外抑制作用最强,青蒿琥酯与卡泊芬净、咪康唑联用对T.asahii有明显的抗真菌增效剂潜力。OBJECTIVE To evaluate the in vitro antifungal effect of artemisinins and its derivants combined with commonly used antifungal agents on Trichosporon asahii(T.asahii) in planktonic and biofilm states. METHODS Totally 15 strains of T.asahii were recruited as the study sujects, the minimum inhibitory concentrations(MICs) of artemisinin, dihydroartemisinin and artesunate against the planktonic T.asahii isolates were determined by micro-broth dilution method, the in vitro inhibiting effects of the most sensitive artemisinin-based drug combined with 5 types of antifungal agents(fluconazole, miconazole, itraconazole, amphotericin B, caspofungin) on planktonic T.asahii isolates and biofilms were determined, and the fractional inhibitory concentration index(FICI) was calculated. RESULTS As compared with artemisinin and dihydroartemisinin, artesunate was the most sensitive to T.asahii. Artesunate combined with caspofungin(73.3%), miconazole(33.3%) and fluconazole(33.3%) had the synergistic effect on planktonic T.asahii. The combination of artesunate and caspofungin(66.7%), miconazole(53.3%), amphotericin B(33.3%) and fluconazole(26.7%) had synergistic effects on T.asahii biofilm. CONCLUSION Artesunate alone has the strongest in vitro antifungal effect on T.asahii. The combination of artesunate and caspofungin and the combination of artesunate and miconazole have obvious potential as antifungal synergist against T.asahii.

关 键 词：青蒿素类 抗真菌药 联合用药 阿萨希毛孢子菌 生物膜 

分 类 号：R379[医药卫生—病原生物学]