Development of an Orogastrointestinal Mucosal Model of Candidiasis with Dissemination to Visceral Organs

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Abstract
Studies were done to develop a murine model that mimics the pattern of mucosal candidiasis followed by disseminated disease seen in patients given cytotoxic chemotherapy. Developmental studies showed that suppression of mice with 5-fluorouracil beginning 3 days prior to infection and given every 7 days thereafter necessitated antibacterial treatment but resulted in a reproducible model. Candida albicans given in the drinking water resulted in oral infection by day 3 that significantly increased from days 10 to 15 and mucosal infection with 4 to 7 log 10 Candida CFU in the esophagus, stomach, small intestine, and cecum. Dissemination to livers occurred and was 100% on days 5 to 15; fewer animals had kidney infection. The median kidney or liver CFU were 2 or 3 log 10 CFU, respectively, on day 15; despite this, mortality was low through 21 days of infection. As a demonstration of the utility of the model to test antifungal activity, daily treatment with 10 or 50 mg/kg itraconazole significantly reduced dissemination to the liver and kidneys and reduced tongue CFU compared to controls. Overall, these studies indicate that a nonlethal model of oral and gastrointestinal mucosal candidiasis with dissemination can be established in mice. Drug efficacy in treating localized infection and in preventing or treating disseminated infection can be studied.