Synergistic antifungal effects and potential mode of action of crisaborole combined with azoles against drug-resistant Candida albicans

2026-06-30

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Dongmei Tan

Qian Deng

Xiao Hou

Kaile Zhai

DOI：10.1080/14787210.2026.2694112

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Candida albicans is the leading pathogen of life-threatening invasive candidiasis, with mortality exceeding 40% in immunocompromised patients. Global azole resistance and limited approved antifungal classes severely restrict clinical treatment, making repurposing FDA-approved drugs a promising low-barrier strategy. The synergistic antifungal activity of crisaborole (CRB) combined with azoles was validated via checkerboard microdilution assay. In vivo efficacy of CRB plus ketoconazole (KCZ) was evaluated in a Galleria mellonella infection model, with mechanisms explored via phenotypic assays and qPCR. CRB combined with azoles exerted potent synergism against drug-resistant C. albicans (FICI 0.023–0.500). CRB+KCZ significantly improved larval survival, reduced fungal burden, inhibited fungal efflux pump activity, and impaired hyphal growth and host cell adhesion of C. albicans. CRB specifically enhances azoles’ antifungal activity, offering a clinically translatable therapeutic strategy for drug-resistant C. albicans infections.

Keywords:

Drug-resistant Candida albicans

ketoconazole

crisaborole

drug combination

synergy

antifungal mechanisms

Synergistic antifungal effects and potential mode of action of crisaborole combined with azoles against drug-resistant Candida albicans

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