Antibiofilm activity of antifungal drugs, including the novel drug olorofim, against Lomentospora prolificans
Antibiofilm activity of antifungal drugs, including the novel drug olorofim, against Lomentospora prolificans
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DOI：
10.1093/jac/dkaa157
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发表时间：
2020-08-01
影响因子：
5.2
通讯作者：
Steinmann, Joerg
中科院分区：
文献类型：
--
作者：
Kirchhoff, Lisa;Dittmer, Silke;Steinmann, Joerg
目的：免疫缺陷或囊性纤维化患者经常遭受呼吸道真菌感染。特别是，生物膜相关真菌引起难治性感染表现，与对抗感染剂的耐药性增加有关。一种新兴的丝状真菌是多产长孢壳菌。在这里，L。方法：对产乳杆菌的生物被膜形成情况进行调查，并分析其对各种抗真菌药物的敏感性。通过结晶紫染色估计增殖素（n = 11），并通过使用XTT测定检测代谢活性生物膜来另外测定生物膜活性。比较了两性霉素B、米卡芬净、伏立康唑和奥洛菲姆在粘附前、粘附后以及在成熟和预先形成的真菌生物膜上添加时的抗真菌膜效果。成像通过共聚焦激光扫描显微镜进行，以证明药物治疗对真菌biofilm.Results的影响：抗生物膜活性的测试抗真菌剂被证明是最有效的贴壁细胞，而成熟的生物膜是最耐药。伏立康唑和奥洛菲姆检测到最有希望的涂膜效果。Olorofim在粘附之前和之后添加时显示平均最小生物膜根除浓度（MBEC）为0.06 mg/L。伏立康唑的MBEC为
Objectives: Patients with immunodeficiency or cystic fibrosis frequently suffer from respiratory fungal infections. In particular, biofilm-associated fungi cause refractory infection manifestations, linked to increased resistance to anti-infective agents. One emerging filamentous fungus is Lomentospora prolificans. Here, the biofilm-formation capabilities of L. prolificans isolates were investigated and the susceptibility of biofilms to various antifungal agents was analysed.Methods: Biofilm formation of L. prolificans (n = 11) was estimated by crystal violet stain and antibiofilm activity was additionally determined via detection of metabolically active biofilm using an XTT assay. Amphotericin B, micafungin, voriconazole and olorofim were compared with regard to their antibiofilm effects when added prior to adhesion, after adhesion and on mature and preformed fungal biofilms. Imaging via confocal laser scanning microscopy was carried out to demonstrate the effect of drug treatment on the fungal biofilm.Results: Antibiofilm activities of the tested antifungal agents were shown to be most effective on adherent cells whilst mature biofilm was the most resistant. The most promising antibiofilm effects were detected with voriconazole and olorofim. Olorofim showed an average minimum biofilm eradication concentration (MBEC) of 0.06 mg/L, when added prior to and after adhesion. The MBECs of voriconazole were