The <i>in vitro</i> activity of iron chelator deferiprone against <i>Candida (Candidozyma) auris</i> in combination with antifungal agents

Candida (Candidozyma) auris is well known for its limited susceptibility to conventional antifungal agents, underscoring the need for novel alternative therapeutic approaches. One such approach, which involves restricting the availability of micronutrients-including iron-is a promising antimicrobial strategy and proven to enhance the efficacy of various antimicrobial agents in vitro. In this study, we evaluated the activity of deferiprone, a clinically approved iron-chelating agent, in combination with echinocandins, amphotericin B and fluconazole against C. auris strains, including three echinocandin-resistant isolates representing the four major clades. Drug-drug interactions were assessed using the chequerboard methodology. Fractional inhibitory concentration index scores ranged from 0.5 to 2.25 and 0.1875 to 4.125 for anidulafungin; 0.375 to 1.5 and 0.125 to 1.5 for micafungin; 0.3125 to 1.5 and 0.3125 to 2 for caspofungin; 0.375 to 2.0625 and 0.375 to 2 for amphotericin B; and 0.625 to 2 and 0.625 to 2 for fluconazole at 24 and 48 h, respectively. Synergistic interactions were most frequently observed with echinocandins, while interactions with fluconazole and amphotericin B were generally additive or indifferent, except in Clade II. Antagonism was observed in only one instance. These findings suggest that iron chelation may potentiate the antifungal activity of echinocandins against C. auris in a clade- and isolate-specific manner.