CD101, A novel echinocandin, possesses potent antibiofilm activity against early and mature Candida albicans biofilms

Abstract

Currently available echinocandins are generally effective against Candida biofilms, but recent emergence of resistance has underscored the importance of developing new antifungal agents that are effective against biofilms. CD101 is a long-acting, novel echinocandin with distinctive pharmacokinetic properties and improved stability and safety relative to other drugs in the same class. CD101 is currently being evaluated as a once-weekly IV infusion for the treatment of candidemia and invasive candidiasis. In this study, we determined: (1) the effect of CD101 against early and mature phase biofilms formed by C. albicans in vitro, and (2) the temporal effect of CD101 on formation of biofilms using time lapse microscopy (TLM). Early or mature phase biofilms were formed on silicone elastomer discs and exposed to the test compounds for 24 h and quantified by measuring their metabolic activity. Separate batches were observed under confocal microscope or used to capture TLM images from 0 to 16 h. Metabolic activity showed that CD101 (0.25 or 1 μg/ml) significantly prevented adhesion phase cells to develop into mature biofilms (P = 0.0062 or 0.0064, respectively), and eradicated pre-formed mature biofilms (P = 0.04 or 0.01, respectively), compared to untreated controls. Confocal microscopy showed significant reduction in biofilm thickness for both early and mature phases (P < 0.05). TLM showed that CD101 stopped the growth of adhestion and early phase biofilms within minutes. CD101-treated hyphae failed to grow into mature biofilms. These results suggest that CD101 may be effective in prevention and treatment of biofilm-associated nosocomial infections.