Treatment and prevention of Candida albicans biofilms with caspofungin in a novel central venous catheter murine model of candidiasis

Objectives: We sought to develop a novel model of central venous catheter (CVC)-associated candidiasis in mice and to use this model to examine the efficacy of caspofungin to treat and prevent Candida albicans biofilms in vivo. Methods: We used catheterized mice, commercially available from the National Cancer Institute, to form C. albicans biofilms inside CVCs. Once the model was developed, we examined the efficacy of caspofungin for the treatment of preformed biofilms and for the prevention of C. albicans biofilm formation. Results: We developed a relatively simple murine model of CVC-associated candidiasis that minimized the number of manipulations necessary for in vivo biofilm formation. C. albicans biofilms formed in vivo display structural features similar to those observed for models of in vitro- and other in vivo-formed biofilms. Following model development, 0.25 mu g/mL of caspofungin was instilled in the catheter to treat preformed biofilms. The results indicated that caspofungin treatment significantly reduced biofilm fungal load in the catheters and dissemination to kidneys compared with untreated controls. In a second set of experiments catheters were pre-treated by filling with 60 mu g/mL of caspofungin before challenge with C. albicans via the CVC. Again, the results indicated a significant reduction in biofilm fungal load and dissemination to kidneys compared with untreated controls. Conclusions: We have developed a novel model of CVC-associated candidiasis in mice. Using this model we demonstrate the efficacy of caspofungin for the treatment and prevention of C. albicans biofilms in vivo.