A Calcineurin Inhibitor as an Enhancer of <i>Candida</i> Susceptibility to Anidulafungin

The increase in invasive candidiasis caused by emerging <i>Candida</i> species presents a significant medical challenge due to their resistance to conventional antifungal treatments. Exploring novel therapeutic strategies, such as drug repurposing, is therefore essential. Tacrolimus, an immunosuppressive calcineurin inhibitor, shows potential antifungal effects. This study investigated the in vitro effect of combining tacrolimus and echinocandin anidulafungin using the checkerboard method against 60 clinical <i>Candida</i> isolates, including <i>Candida albicans</i>, <i>Candida auris</i>, <i>Candida glabrata</i>, and <i>Candida parapsilosis</i>. Time-kill assays against <i>C. parapsilosis</i> clinical isolates with <i>FKS1</i> gene mutations were conducted. Checkerboard data revealed that tacrolimus reduced anidulafungin MIC values: a synergistic activity was observed against 90% of the isolates studied, with a particularly notable effect against multidrug-resistant <i>C. auris</i>, showing 100% synergy. Positive outcomes were corroborated by time-kill assays. Hence, the addition of tacrolimus may enhance susceptibility to anidulafungin, as suggested by checkerboard and time-kill assays conducted against <i>C. parapsilosis</i>, including isolates harboring mutations in <i>FKS1</i>. These promising findings are a starting point for future studies on the antifungal properties of tacrolimus and related compounds.