Development of an Immunosuppressed, Catheterized Murine Model for Ascending Candida albicans Urinary Tract Infection

Abstract

610 To study ascending urinary tract infection with Candida albicans in the solid organ transplant recipient, a bladder catheterized mouse model was developed. An indwelling catheter segment was inserted into the bladder of female CBA/J mice; two weeks later (day 0) C. albicans infection was established by transurethral inoculation. Half of the animals also received immunosuppression with cyclosporine A (10 mg/kg/day by gavage) and hydrocortisone (equivalent to prednisone 1 mg/kg/day IP) from day -3 to day 7. A persistent infection could be established in both immunosuppressed and nonimmunosuppressed (control) mice, with immunosuppressed mice having significantly higher CFU / gram of tissue in the kidney than controls by day 7(p<.02). In dose ranging experiments in which animals received 103 - 108 CFU of C. albicans per inoculum, the ID50 was determined to be 2.69 × 105 CFU for immunosuppressed mice and 4.07 × 105 CFU for controls; the size of the inoculum correlated directly with the proportion of immunosuppressed mice having culture-proven infection of various tissues (R2 = 0.91, 0.93, and 0.95 for bladder, kidney and spleen, respectively; p<.05 for each). Although mortality did not differ significantly between the two groups of mice [10.6% in immunosuppressed mice vs. 3.3% in normal animals (p =.167)], immunosuppressed mice given an inoculum of 105 CFU were more likely to have disseminated infection than control animals (p =.002), as well as a greater number of organisms cultured from kidney tissue (p =.0002) and more extensive medullary invasion by histology (p =.001). This catheterized mouse model lends itself to wide application for the study of ascending Candida urinary tract infection in immunosuppressed hosts, including determination of pathophysiology and the testing of antifungal agents for prophylaxis and treatment.