Expert review of anti-infective therapy · 2026
Synergistic antifungal effects and potential mode of action of crisaborole combined with azoles against drug-resistant Candida albicans.
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Duan Ximeng, Tan Dongmei, Deng Qian, Hou Xiao, Liu Lin, Zhai Kaile, Li Xiuyun
Аннотация
BACKGROUND: 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.
RESEARCH DESIGN AND METHODS: 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.
RESULTS: 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.
CONCLUSIONS: CRB specifically enhances azoles' antifungal activity, offering a clinically translatable therapeutic strategy for drug-resistant C. albicans infections.
RESEARCH DESIGN AND METHODS: 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.
RESULTS: 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.
CONCLUSIONS: CRB specifically enhances azoles' antifungal activity, offering a clinically translatable therapeutic strategy for drug-resistant C. albicans infections.