Introduction. Cryptococcus species are pathogens commonly associated with cases of meningoencephalitis in individuals who are immunosuppressed due to AIDS. Aim. The aim was to evaluate the effects of the antiretroviral darunavir alone or associated with fluconazole, 5-flucytosine and amphotericin B against planktonic cells and biofilms of Cryptococcus species. Methodology. Susceptibility testing of darunavir and the common antifungals against 12 members of the Cryptococcus neoformans/Cryptococcus gattii species complex was evaluated by broth microdilution. The interaction between darunavir and antifungals against planktonic cells was tested by a checkerboard assay. The effects of darunavir against biofilm metabolic activity and biomass were evaluated by the XTT reduction assay and crystal violet staining, respectively. Results. Darunavir combined with amphotericin B showed a synergistic interaction against planktonic cells. No antagonistic interaction was observed between darunavir and the antifungals used. All Cryptococcus species strains were strong biofilm producers. Darunavir alone reduced biofilm metabolic activity and biomass when added during and after biofilm formation (P<0.05). The combination of darunavir with antifungals caused a significant reduction in biofilm metabolic activity and biomass when compared to darunavir alone (P<0.05). Conclusion. Darunavir presents antifungal activity against planktonic cells of Cryptococcus species and synergism with amphotericin B. In addition, darunavir led to reduced biofilm formation and showed activity against mature biofilms of Cryptococcus species. Activity of the antifungals against mature biofilms was enhanced in the presence of darunavir.

中文翻译：

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Darunavir抑制新型隐球菌/加蒂隐球菌物种复合物的生长，并增加生物膜对抗真菌药物的敏感性。

介绍。 隐球菌是在因艾滋病而受到免疫抑制的个体中通常与脑膜脑炎病例相关的病原体。目标。目的是评估单独或与氟康唑，5-氟胞嘧啶和两性霉素B联合使用的抗逆转录病毒地雷那韦对隐球菌物种的浮游细胞和生物膜的影响。方法。darunavir的药敏试验和对新型隐球菌/加蒂隐球菌12个成员的常见抗真菌药肉汤微稀释法评估物种复合物。通过棋盘分析法测试了地雷纳韦和抗浮游细胞的真菌之间的相互作用。分别通过XTT还原测定和结晶紫染色评估了darunavir对生物膜代谢活性和生物量的影响。结果。Darunavir与两性霉素B结合显示出对浮游细胞的协同作用。在达那那韦和所用抗真菌剂之间未观察到拮抗作用。所有隐球菌属菌株都是强大的生物膜生产者。当在生物膜形成期间和之后添加时，仅达那那韦单独降低生物膜代谢活性和生物量（P<0.05）。与单独使用达那韦相比，达那那韦与抗真菌剂的组合导致生物膜代谢活性和生物量显着降低（P <0.05）。结论。Darunavir表现出对隐球菌物种的浮游细胞的抗真菌活性以及与两性霉素B的协同作用。此外，darunavir导致生物膜形成减少，并显示出对隐球菌物种的成熟生物膜的活性。在达那那韦的存在下，抗真菌药对成熟生物膜的活性增强。