title: In vitro synergy of pseudolaric acid B and fluconazole against clinical isolates of Candida albicans.
abstract: 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 using the time-killing test for the selected strains. Fluconazole and PAB exhibited a good synergism against azole-R isolates of C. albicans.
authors.affiliation: Key Laboratory of Zoonosis Research, Ministry of Education, Institute of Zoonosis, College of Animal Science and Veterinary Medicine, Jilin University, Changchun, China.
authors.forename: Na
authors.initials: N
authors.lastname: Guo
authors.forename: Guanghui
authors.initials: G
authors.lastname: Ling
authors.forename: Xiaoying
authors.initials: X
authors.lastname: Liang
authors.forename: Jing
authors.initials: J
authors.lastname: Jin
authors.forename: Junwen
authors.initials: J
authors.lastname: Fan
authors.forename: Jiazhang
authors.initials: J
authors.lastname: Qiu
authors.forename: Yu
authors.initials: Y
authors.lastname: Song
authors.forename: Ning
authors.initials: N
authors.lastname: Huang
authors.forename: Xiuping
authors.initials: X
authors.lastname: Wu
authors.forename: Xuelin
authors.initials: X
authors.lastname: Wang
authors.forename: Xuming
authors.initials: X
authors.lastname: Deng
authors.forename: Xuliang
authors.initials: X
authors.lastname: Deng
authors.forename: Lu
authors.initials: L
authors.lastname: Yu
mesh_terms: D000935:Antifungal Agents / Q000494:pharmacology*; D002176:Candida albicans / Q000187:drug effects* / Q000302:isolation & purification; D002177:Candidiasis / Q000382:microbiology; D004224:Diterpenes / Q000494:pharmacology*; D004357:Drug Synergism; D015725:Fluconazole / Q000494:pharmacology*; D006801:Humans; D008826:Microbial Sensitivity Tests; D050296:Microbial Viability / Q000187:drug effects; D013997:Time Factors
chemical_list: D000935:Antifungal Agents; D004224:Diterpenes; C058391:pseudolaric acid B; D015725:Fluconazole