卡斯波芬金
白色体
白色念珠菌
联合疗法
微生物学
利巴韦林
药理学
最小抑制浓度
棋盘
化学
医学
两性霉素B
抗真菌
生物
抗菌剂
免疫学
丙型肝炎病毒
病毒
作者
Yuting Wang,Haiying Yan,Jinfeng Li,Yuan Zhang,Zhen Wang,Shujuan Sun
标识
DOI:10.1016/j.ijantimicag.2023.106709
摘要
The number of invasive fungal infections has increased dramatically, resulting in high morbidity and mortality among immunocompromised patients. With increasing use of caspofungin (CAS), resistant strains have emerged frequently and led to limitations in the treatment of patients with severe invasive Candida albicans infections. Combination therapy is an important method to deal with this issue. As such, this study investigated the activity of CAS in combination with ribavirin (RBV) against C. albicans. The results of this in-vitro study showed that the minimum inhibitory concentrations (MICs) of CAS and RBV when they were used as monotherapy were 0.5-1 μg/mL and 2-8 μg/mL, respectively, while the MIC of CAS decreased from 0.5-1 μg/mL to 0.0625-0.25 μg/mL when used in combination with RBV, with a fractional inhibitory concentration index (FICI) ≤0.5. In addition, the RBV + CAS combination group displayed synergistic effects against C. albicans biofilm over 4 h; the sessile MIC (sMIC) of CAS decreased from 0.5-1 µg/mL to 0.0625-0.25µg/mL and the sMIC of RBV decreased from 4-16 µg/mL to 1-2 µg/mL, with FICI <0.5. The survival of C. albicans-infected Galleria mellonella was prolonged, the fungal burden was decreased, and the area of tissue damage was reduced after combination therapy. Further study showed that the mechanisms of action of the synergistic effect were related to the inhibition of biofilm formation, the inhibition of hyphal growth, and the activation of metacaspases, but were not related to the accumulation of reactive oxygen species. It is hoped that these findings will contribute to the understanding of drug resistance in C. albicans, and provide new insights for the application of RBV.
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