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

  • Expert Rev Anti Infect Ther. 2026 Jun 30:1-12. doi: 10.1080/14787210.2026.2694112.
Ximeng Duan  1 ,  Dongmei Tan  2 ,  Qian Deng  3 ,  Xiao Hou  4 ,  Lin Liu  1 ,  Kaile Zhai  1  5 ,  Xiuyun Li  1
Affiliations
  • 1. Infection and Microbiology Research Laboratory for Women and Children, Shandong Provincial Maternal and Child Health Care Hospital Affiliated to Qingdao University, Jinan, P.R. China.
  • 2. Traditional Chinese Medicine Department, Shandong Provincial Maternal and Child Health Care Hospital Affiliated to Qingdao University, Jinan, P.R. China.
  • 3. Obstetrics and Gynecology Department, Shandong Provincial Maternal and Child Health Care Hospital Affiliated to Qingdao University, Jinan, P.R. China.
  • 4. Diagnosis and Treatment Center for Pelvic Floor Disease, Shandong Provincial Maternal and Child Health Care Hospital Affiliated to Qingdao University, Jinan, P.R. China.
  • 5. School of Pharmacy, Qingdao University, Qingdao, P.R. China.
PMID: 42334844 DOI: 10.1080/14787210.2026.2694112
Abstract

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.

Keywords
Drug-resistant Candida albicans; antifungal mechanisms; crisaborole; drug combination; ketoconazole; synergy.
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