Aspergillus fumigatus (A. fumigatus) is the most common airborne opportunistic fungal pathogen. Biofilm formation is one of the main pathogenic mechanisms of A. fumigatus. During the past decades, A. fumigatus azole resistance has become prevalent due to the medical and agricultural use of antifungal drugs and fungicides. Until now, the role of fungal biofilms in azole resistance of A. fumigatus remains unclear. In the present study, we compared biofilm drug susceptibility and biofilm formation under itraconazole of azole-resistant strains, sensitive strains, and standard strains, separately. The biofilm viability and matrix thickness at the early and the late stage were measured by XTT assay and Calcofluor white. Our results showed that the sessile minimum inhibitory concentration of itraconazole, which describing the inhibition of drugs on fungi sessile with biofilm, was much higher than the traditional minimal inhibitory concentration of itraconazole. Additionally, low concentrations of itraconazole inhibited biofilm formation of A. fumigatus strains. Notably, biofilm formation by azole-resistant strains could not be inhibited by high concentrations of itraconazole but could be effectively restrained by low concentrations of micafungin, revealing the efficacy of a cell-wall inhibitor to disrupt A. fumigatus biofilm formation. However, late-stage biofilms of both azole-resistant strains and standard strains were hard to disrupt using itraconazole. We found that itraconazole was effective to prevent A. fumigatus biofilm formation at the early stage. For the treatment of A. fumigatus biofilm, our findings suggest that an early-stage preventive strategy is preferred and micafungin is effective to control the azole-resistant strain infection.

烟曲霉（A. fumigatus）是最常见的空气传播机会性真菌病原体。生物膜形成是烟曲霉的主要致病机制之一。在过去的几十年中，由于抗真菌药物和杀真菌剂的医疗和农业使用，烟曲霉唑耐药性变得普遍。迄今为止，真菌生物膜在烟曲霉唑抗性中的作用还不清楚。在本研究中，我们分别比较了唑类耐药菌株、敏感菌株和标准菌株在伊曲康唑下的生物膜药物敏感性和生物膜形成。通过XTT法和Calcofluor白色测量早期和晚期的生物膜活力和基质厚度。我们的研究结果表明，描述药物对具有生物膜的无柄真菌的抑制作用的伊曲康唑的固着最小抑菌浓度远高于传统的伊曲康唑最小抑菌浓度。此外，低浓度的伊曲康唑可抑制烟曲霉的生物膜形成菌株。值得注意的是，唑类耐药菌株的生物膜形成不能被高浓度的伊曲康唑抑制，但可以被低浓度的米卡芬净有效抑制，揭示了细胞壁抑制剂破坏烟曲霉生物膜形成的功效。然而，使用伊曲康唑很难破坏唑类耐药菌株和标准菌株的晚期生物膜。我们发现伊曲康唑在早期可有效防止烟曲霉生物膜形成。对于烟曲霉生物膜的治疗，我们的研究结果表明，早期预防策略是首选，米卡芬净可有效控制唑类耐药菌株感染。