Studies on Intra-abdominal Fungal Infections

Abstract

Even though Intra-abdominal fungal Infections (IAFIs) have been recognized with increasing frequency and high morbidity and mortality rates it remains poorly understood. The present study aims to investigate the epidemiology of the disease, the virulence and the in vivo and in vitro susceptibility of the causal agents associated with IAFIs; to predict the frequency, the outcome of the clinical infection and response to antifungal therapy. 143 patients with intra-abdominal infections (IAIs) were included in this study, fungi were found to be the causal agents of 39.2% of the cases (56 cases), while bacteria represented 60.8% of the cases (87 cases). Organ transplantation and peritoneal dialysis represented the major risk factors for IAFIs, with secondary peritonitis and liver abscess being the most frequently encountered clinical presentations. Yeast fungi represented the causal agents of 53.6% of the cases, while filamentous fungi represented only 46.4%. All the yeast isolated from the cases were non-Candida albicans (NCA) species. Candida parapsilosis represented the most prevalent species (40%), followed by Candida guilliermondii (30%), Candida glabrata (13.3%), Candida tropicalis (13.3%) and Candida lipolytica (3.3%). Aspergillus group represented the most prevalent filamentous fungi. Aspergillus flavus represented the most prevalent species isolated from 42.3% of the cases, followed by Aspergillus fumigatus (30.8%), Aspergillus nidulans (7.7%), Mucor circinelloides (7.7%), Aspergillus niger (3.8%), Acremonium strictum (3.8%) and Scopulariopsis koningii (3.8%). On testing the in vitro antifungal susceptibility, voriconazole was the most effective drug against C. parapsilosis, C. guilliermondii and C. lipolytica. Micafungin showed the best efficacy against C. tropicalis and C. glabrata. For filamentous strains, micafungin was the most effective antifungal drug against Aspergillus species, while amphotericin B was the most effective against M. circinelloides and voriconazole was effective against both A. strictum and S. koningii. In the in vivo model of infection, both immunosuppressed and immunocompetent female CD-1 mice were challenged intraperitoneally with five NCA strains: C. glabrata, C. parapsilosis, C. lipolytica, C. tropicalis and C. guilliermondii; and seven filamentous strains: A. flavus, A. fumigatus, A. nidulans, A. niger, M. circinelloides, A. strictum and S. koningii. Mice were closely observed for symptoms. Treated groups received voriconazole (40 mg/kg/day) or micafungin (10 mg/kg/day), amphotericin B (10 mg/kg/day) 24 h after infection depending on in vitro susceptibility results. Survival rates, mean survival time and fungal tissue burdens were recorded for all groups. All infected groups developed hepatosplenomegaly, peritonitis and multiple abscesses on intra-abdominal organs and mesenteries, with high mortality rates especially among immunosuppressed groups. All treated immunocompetent animals survived the entire duration of experiments (0% mortality rates), while treated immunosuppressed mice kept relatively high mortality rates (20-60%). Treatment failed to eradicate the infection in case of immunosuppressed mice infected with all Candida species, A. flavus, A. fumigatus and M. circinelloides, despite the significant decrease of the fungal burden and increase of the mean survival time. This study reported an increasing pathogenicity of the recovered pathogens compared to that reported in literature.