In vitro synergy of pseudolaric acid B and fluconazole against clinical isolates of Candida albicans

作者：Na Guo, Guanghui Ling, Xiaoying Liang, Jing Jin, Junwen Fan, Jiazhang Qiu, Yu Song, Ning Huang, Xiuping Wu, Xuelin Wang, Xuming Deng, Xuliang Deng, Xuliang Deng, Xuliang Deng, Lu Yu · 发表于：Mycoses · 年份：2010 · DOI：10.1111/j.1439-0507.2010.01935.x · 被引用次数：22 · 研究领域：Biological Activity of Diterpenoids and Biflavonoids、Fungal Plant Pathogen Control、Nail Diseases and Treatments

Candida albicans is the most common fungal pathogen in humans. The emergence of resistance to azole antifungals has raised the issue of using such antifungals in combination to optimise therapeutic outcome. The objective of this study was to evaluate in vitro synergy of pseudolaric acid B (PAB) and fluconazole (FLC) against clinical isolates of C. albicans. The in vitro antifungal activity of PAB, a diterpene acid from Pseudolarix kaempferi Gordon, was evaluated alone and in combination with FLC against 22 FLC-resistant (FLC-R) and 12 FLC-susceptible (FLC-S) C. albicans using the chequerboard microdilution method and time-killing test assays. Synergism was observed in all 22 (100%) FLC-R strains tested as determined by both fractional inhibitory concentration index (FICI) with values ranging from 0.02 to 0.13 and bliss independence (BI) models. Synergism was observed in two of 12 (17%) FLC-S strains as determined by FICI model with values ranging from 0.25 to 0.5 and in three of 12 (18%) FLC-S strains as determined by BI model. For FLC-R strains, the drug concentrations of FLC and PAB, where synergistic interactions were found, ranged from 0.06 to 4 μg ml(-1) and 0.5 to 4 μg ml(-1) respectively. For FLC-S strains, the drug concentrations of FLC and PAB were 1-8 μg ml(-1) and 0.5-4 μg ml(-1) respectively. The BI model gave results consistent with FICI, but no antagonistic activity was observed in any of the strains tested. These interactions between PAB and FLC were confirmed ...