| Abstract [eng] |
Introduction: Candida species cause 6,3% of all hospital infections, however, they are responsible for 22% of systemic candidemia cases which result in 19-24% mortality rate. Candida biofilms are more resistant to drugs in comparison with planktonic forms. For that reason, it is important to seek for new treatment opportunities. Catheters, immunosuppression and prolonged antibiotic use are the main risk factors of biofilms producing C. albicans infections. Aim: To investigate the antimicrobial interactions between polyphenols, triterpenoids and fatty acid derivatives in combination with Amphotericin B (AmB) and Fluconazole (Flu) against C. albicans biofilms. Materials and methods: Biofilm production in C. albicans was quantified by crystal violet assay. CLSI (M38-A2) broth microdilution methodology was used to determine MICs for Flu, AmB, rosmarinic acid (R), pentacyclic triterpenoid (betulinic acid, B), fatty acid (oleic acid, O) against 3 isolates of planktonic and biofilm associated C. albicans. Viability of C. albicans was determined using AlamarBlue assay. Viable C. albicans quantified by serial dilution and plating. Synergistic relations of drugs were analyzed by fractional inhibitory concentration (FIC) determination. Results: Both planktonic and biofilm associated C. albicans showed high level resistance to Flucanozole (MIC>200 µg /mL). Planktonic forms and biofilms were both equally sensitive to AmB (MIC 0.1 µg/mL ). AmB versus its combination with rosmarinic acid (MICAmB/ R= 0.01/5.7 µg/mL) had significantly decreased biofilm formation (OD600 nm 1.291 versus 0.866, p=0.0119, α=0.05), which refers to synergistic drug relation (ΣFIC=0.10099). Moreover, rosmarinic acid in combination with Fluconazole (MIC Flu/R= 20/570 µg/mL, OD600 nm 0.585, p=0.0024) showed synergistic impact on biofilms (ΣFIC=0.199). Other single and combined antifungals did not show statistically significant impact on C. albica[...]. |
