Cecal colonization and systemic spread of Candida albicans in mice treated with antibiotics and dexamethasone

Infections with Candida albicans have become a significant problem among very low birth weight infants in the neonatal intensive care unit. Risk factors are multiple and include administration of antibiotics and glucocorticoids, such as dexamethasone. Experiments were designed to study the combined effect of oral broad-spectrum antibiotics and parenteral dexamethasone on cecal colonization and extraintestinal dissemination of C. albicans in separate groups of mice that were orally inoculated with one of four C. albicans strains that were either wild-type INT1/INT1 or had one or more disruptions of the INT1 gene. Intestinal colonization was monitored by quantitative culture of the mouse cecum, and extraintestinal invasion was monitored by quantitative culture of the draining mesenteric lymph nodes and kidneys. At sacrifice, the average numbers of cecal C. albicans differed from 7.7 log(10)/g to 6.7 log(10)/g (p < 0.01) in mice orally inoculated with C. albicans containing two functional copies of INT1 and no functional copies of INT1, respectively. The incidence of extraintestinal dissemination to mesenteric lymph nodes and kidneys correspondingly varied from 57 to 13% (p < 0.01) and 83 to 4% (p < 0.01) in mice inoculated with these two C. albicans strains. Mice orally inoculated with C. albicans containing one functional copy of INT1 had intermediate levels of cecal colonization and extraintestinal dissemination. Thus, cecal colonization and extraintestinal dissemination of C. albicans was facilitated in antibiotic-treated mice given dexamethasone. In addition, the presence of two functional copies of the INT1 gene was associated with the greatest levels of cecal colonization and extraintestinal dissemination of C. albicans.