抗真菌药单用及联合体外抗皮炎外瓶霉生物膜效应

In vitro antifungal activity of four antifungal agents alone or in combination against Exophiala dermatitidis biofilms

目的 检测抗真菌药单用及联合对皮炎外瓶霉生物膜的体外抗真菌活性。方法 96孔板构建皮炎外瓶霉生物膜，通过棋盘式微量液基稀释法，检测两性霉素B、伏立康唑、伊曲康唑及卡泊芬净单用或联合抗皮炎外瓶霉生物膜的活性。结果 伊曲康唑、伏立康唑及卡泊芬净对皮炎外瓶霉生物膜50%和80%最低抑菌浓度（SMIC50、SMIC80）均 〉 32 mg/L，两性霉素B的SMIC50为1 - 2 mg/L，SMIC 80为4 - 8 mg/L。两性霉素B与伏立康唑联合抗皮炎外瓶霉生物膜有协同效应；两性霉素B与伊曲康唑或卡泊芬净联合，以及伏立康唑与卡泊芬净联合对皮炎外瓶霉生物膜均无协同作用；所有组合均未见拮抗效应。结论 两性霉素B具有较好的抗皮炎外瓶霉生物膜活性，与伏立康唑联合能够增强对皮炎外瓶霉生物膜的杀伤作用。

Objective To evaluate the in vitro antifungal activity of 4 antifungal agents alone or in combination against Exophiala dermatitidis （E. dermatitidis） biofilms. Methods E. dermatitidis biofilms were prepared by using a modified 96-well plate-based method. The in vitro antifungal activity of amphotericin B, voriconazole, itraconazole and caspofungin alone or in combination against E. dermatitidis biofilms were investigated via the broth microdilution checkerboard technique. Results The sessile minimum inhibitory concentration ranges resulting in 50% （SMIC50） and 80% inhibition （SMIC80） of E. dermatitidis biofilms were all 〉 32 mg/L for itraconazole, voriconazole and caspofungin, and the SMIC50 and SMIC80 ranges of amphotericin B were 1 - 2 mg/L and 4 - 8 mg/L respectively. The combination of amphotericin B with voriconazole showed synergistic inhibitory effects against E. dermatitidis biofilms, while the combination of amphotericin B with itraconazole or caspofungin, as well as the combination of voriconazole with caspofungin, revealed no synergistic effects. No antagonistic effect was observed in any of the combinations. Conclusion Amphotericin B appears more active against E. dermatitidis biofilms, and the combination with voriconazole can enhance the anti-biofilm effects against E. dermatitidis biofilms.