Synergistic antifungal activity of statin-azole associations as witnessed by Saccharomyces cerevisiae- and Candida utilis-bioassays and ergosterol quantification.
作者： María Eugenia Cabral , Lucía IC Figueroa , Julia I Fariña , None
DOI: 10.1016/J.RIAM.2012.09.006
关键词:
摘要: a b s t r c Background: Frequent opportunist fungal infections and the resistance to available antifungal drugs promoted development of new alternatives for treatment, like drug combinations. Aims: This work aimed detect synergism between statins azoles by means an agar-well diffusion bioassay with Saccharomyces cerevisiae ATCC 32051 Candida utilis Pr1-2 as test strains. Methods: Synergistic effects were tested simultaneously adding sub inhibitory concen- tration (SIC) statin (atorvastatin, lovastatin, pravastatin, rosuvastatin or simvastatin) plus minimal concentration (MIC) azole (clotrimazole, fluconazole, itraconazole, ketoconazole micona- zole) yeast-embedded YNB agar plates, positive result corresponded yeast growth inhibition halo higher than that produced MIC alone. Yeast cell ergosterol quantification RP-HPLC was used confirm statin-azole synergism, rescue bioassays performed evaluating statin-induced synthesis blockage. Results: Growth significantly increased when clotrimazole, keto- conazole miconazole combined atorvastatin, simvastatin. Highest increments observed on S. (77.5%) C. (43.2%) SIC simvastatin miconazole, i.e. 4 + 2.4 g/ml 20 4.8 g/ml, respectively. Pravastatin showed almost no significant (0-7.6% increase). interaction ratios agents simvastatin-miconazole combinations indicative syner- gism. Synergism also confirmed reduction in cellular levels (S. cerevisiae, 40% utilis, 22%). Statin-induced blockage corroborated ergos- terol bioassays, pravastatin being most easily abolished whilst
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