Experimental murine model of intra-abdominal infections caused by some non-albicans <i>Candida</i> species

Abstract

Background: Even though intra-abdominal candidiasis (IAC) has been increasingly recognized, with associated high morbidity and mortality rates, its pathogenesis remains poorly understood. This model aims to study the pathogenicity and invivo susceptibility of non-albicans Candida species associated with IAC in human in order to predict the frequency of infections, outcome of clinical disease and response to antifungal therapy.

Methodology: Both immunosuppressed and immunocompetent female CD-1 mice were challenged intraperitoneally with 5 x 10⁸ CFU/ml inoculum of five non-albicans Candida strains; Candida glabrata, Candida parapsilosis, Candida lipolytica, Candida tropicalis and Candida guilliermondii. Mice were closely observed for symptoms. Treated groups received voriconazole (40 mg/kg/day) or micafungin (10 mg/kg/day) 24 hours after infection depending on invitro susceptibility results. Survival rate, mean survival time and fungal tissue burdens were recorded for all groups.

Results: All infected groups developed hepatosplenomegaly, peritonitis and multiple abscesses on intra-abdominal organs and mesenteries. C. glabrata and C. lipolytica represented the most and the least virulent strains respectively in terms of survival rate, mean survival time and fungal burden in both immunosuppressed and immunocompetent models. Following treatment, all immunocompetent animals survived the entire duration of experiments (0% mortality rate), while mortality rate was relatively high (20-60%) in immunosuppressed mice. Treatment failed to eradicate the infection in immunosuppressed mice despite significant decrease of the fungal burden and increase mean survival time.

Conclusion: This study reports an increasing pathogenicity of non-albicans Candida species, with persistent infection among immunosuppressed animals.

Keywords: Intra-abdominal, Candidiasis, non-albicans, invivo, mice