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

IF 4.6 2区医学 Q1 INFECTIOUS DISEASES

Expert Review of Anti-infective Therapy Pub Date : 2026-08-01 Epub Date: 2026-06-30 DOI:10.1080/14787210.2026.2694112

Ximeng Duan, Dongmei Tan, Qian Deng, Xiao Hou, Lin Liu, Kaile Zhai, Xiuyun Li

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引用次数: 0

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.

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crisaborole联合唑类药物对耐药白色念珠菌的协同抗真菌作用及其潜在机制。

背景：白色念珠菌是危及生命的侵袭性念珠菌病的主要病原体，免疫功能低下患者的死亡率超过40%。全球唑耐药性和有限批准的抗真菌药物严重限制了临床治疗，使fda批准的药物成为一种有希望的低屏障策略。研究设计与方法：采用棋盘微稀释法验证crisaborole （CRB）与唑类药物的协同抑菌活性。在mellonella Galleria感染模型中评估CRB +酮康唑（KCZ）的体内疗效，并通过表型分析和qPCR探索其机制。结果：CRB联合唑类药物对耐药白色念珠菌具有较强的增效作用（FICI 0.023 ~ 0.500）。CRB+KCZ显著提高了白念珠菌的幼虫存活率，降低了真菌负荷，抑制了真菌外排泵活性，损害了白念珠菌的菌丝生长和宿主细胞粘附。结论：CRB特异性增强了唑类药物的抗真菌活性，为耐药白色念珠菌感染提供了一种临床可翻译的治疗策略。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Expert Review of Anti-infective Therapy 医学-药学

CiteScore

11.20

自引率

0.00%

发文量

审稿时长

4-8 weeks

期刊介绍： Expert Review of Anti-Infective Therapy (ISSN 1478-7210) provides expert reviews on therapeutics and diagnostics in the treatment of infectious disease. Coverage includes antibiotics, drug resistance, drug therapy, infectious disease medicine, antibacterial, antimicrobial, antifungal and antiviral approaches, and diagnostic tests.