P032 Efficacy of novel azole compounds (ATTAF-1 and ATTAF-2) against Candida albicans in a murine model of invasive Candidiasis

Abstract

Poster session 1, September 21, 2022, 12:30 PM - 1:30 PMObjectives Candida albicans is the most common cause of nosocomial bloodstream infections and are associated with substantial morbidity and mortality in immunocompromised individuals. However, limited therapeutic approaches against invasive candidiasis are available. The rise in antifungal resistance highlights the urgent need to develop new therapeutic options and novel treatment strategies to combat later infections. A novel compound Aryl-1, 2, 4-triazol-3- ylthio, fluconazole alcohol-derived analogs (ATTAFs), has newly developed with potent in vitro activity against Candida species, including fluconazole-resistant isolates. The objective of this study was to further evaluate the in vivo effectiveness in a murine model of invasive candidiasis due to C. albicans.MethodsTreatment with ATTAF-1 and ATTAF-2 significantly increased the survival of infected mice compared to the control group (5% DMSO plus inoculum).ResultsThe antifungal action of ATTAF-1 and ATTAF-2 and their median survival time provided no evidence of a difference versus fluconazole. Although there was an obvious fungal load (mean log CFU/g of tissue) decrease by ATTAF-1 and ATTAF-2 in the kidney, spleen, and liver of the treated mice in comparison with the control group and not similar to each other in regard of the dose, fluconazole showed a significant decrease in the number of fungal loads, similar to the group treated with ATTAF-1 and ATTAF-2. Nevertheless, the results of this study indicate that the use of ATTAF-1 and ATTAF-2 as a therapeutic agent can exert significant in vitro and in vivo antifungal effects against C. albicans, increasing animal survival and significantly decreasing fungal loads.ConclusionAlthough we have identified two new compounds, ATTAF-1 and ATTAF-2, as novel promising Candidates for the treatment of Candida infection, more studies of ATTAF-1 and ATTAF-2 activity and their action mechanisms in animal models are warranted to enhance our understanding and establish their efficacy.