Ambisome shows potent anti-Candida auris in vitro and in vivo activity

Abstract

Candida auris is an emerging multidrug resistant Candida species that has been reported in many parts of the world for causing severe illness in hospitalized patients especially bloodstream infections. The challenge with this type of yeast is its resistance to commonly used antifungal drugs, thus identifying antifungals that are effective against this species is critical. In this study, we determined the in vitro activity of Ambisome against 35 clinical isolates of C. auris using minimum inhibitory concentration (MIC) assay as well as the efficacy of Ambisome compared to Amphotericin B and fluconazole using a C. auris murine disseminated model. Antifungal activity of C. auris against Ambisome and comparators was assessed using amicrodilution method performed according to the Clinical and Laboratory Standard Institute (CLSI) M27-A4 methodology. Mice were immunocompromised and challenged with 3 x 107 C. auris blastopores in 0.1 ml of normal saline (via the tail vein). Treatment efficacy was assessed by determining reductions in mortality as well as decrease in tissue fungal burden (CFUs). Ambisome showed lower MIC50 and MIC90 values (1 and 2 μg/mL, respectively) than the comparators tested. Significant efficacy was observed in the Ambisome 7.5 mg/kg -treated group (100% and 90% survival by day 7- and 14-days post inoculation, respectively). Additionally, Ambisome and fluconazole treated groups showed significant reduction in CFUs in the kidneys (P- values of 0.028 and 0.022, respectively) compared to the untreated group. Our data shows that Ambisome shows significant antifungal activity against C. auris in vitro as well as in vivo.