Institute of Medical Microbiology, Excellence Center for Medical Mycology (ECMM), University Hospital Essen, University of Duisburg-Essen, Essen, Germany.
Department of Internal Medicine, University of Cologne, Faculty of Medicine and University Hospital Cologne, Excellence Center for Medical Mycology (ECMM), Cologne, Germany.
Microbiol Spectr. 2023 Jun 15;11(3):e0513022. doi: 10.1128/spectrum.05130-22. Epub 2023 Apr 5.
Infections with spp. and Lomentospora prolificans have become a serious threat in clinical settings. The high mortality rates associated with these infections can be correlated with their multidrug resistance. The development of alternative treatment strategies has become crucial. Here, we investigate the and activity of luliconazole (LLCZ) against Scedosporium apiospermum (including its teleomorph Pseudallescheria boydii) and . The LLCZ MICs were determined for a total of 37 isolates (31 isolates, 6 Scedosporium apiospermum/ strains) according to EUCAST. Furthermore, the LLCZ antifungal activity was tested , using an XTT [2,3-bis-(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide salt] growth kinetics assay and biofilm assays (crystal violet and XTT assay). In addition, a Galleria mellonella infection model was used for treatment assays. The MIC of LLCZ was determined to be 0.25 mg/L for all tested pathogens. Growth was inhibited within 6 to 48 h of the start of incubation. LLCZ inhibited biofilm formation in both preadhesion stages and late-stage adhesion. , a single dose of LLCZ increased the survival rate of the larvae by 40% and 20% for and spp., respectively. This is the first study demonstrating LLCZ activity against and and the first study showing the antibiofilm effect of LLCZ in spp. and S. apiospermum are opportunistic, multidrug-resistant pathogens causing invasive infections in immunosuppressed patients and sometimes in healthy persons. is panresistant against the currently available antifungals, and both species are associated with high mortality rates. Thus, the discovery of novel antifungal drugs exhibiting an effect against these resistant fungi is crucial. Our study shows the effect of luliconazole (LLCZ) against and spp. , as well as in an infection model. These data reveal the previously unknown inhibitory effect of LLCZ against and its antibiofilm effect in spp. It represents an extension of the literature regarding azole-resistant fungi and could potentially lead to the development of future treatment strategies against these opportunistic fungal pathogens.
spp. 和 Lomentospora prolificans 的感染已成为临床环境中的严重威胁。这些感染的高死亡率与它们的多药耐药性有关。开发替代治疗策略变得至关重要。在这里，我们研究了卢立康唑（LLCZ）对 Scedosporium apiospermum（包括其同物 Pseudallescheria boydii）和 的杀菌和抑菌活性。根据 EUCAST，共对 37 株分离株（31 株 Scedosporium apiospermum/ 株）确定了 LLCZ 的 MIC。此外，使用 XTT [2,3-双（2-甲氧基-4-硝基-5-磺苯基）-2H-四唑-5-羧基苯胺盐]生长动力学测定法和生物膜测定法（结晶紫和 XTT 测定法）测试了 LLCZ 的抗真菌活性。此外，还使用 Galleria mellonella 感染模型进行了 治疗测定。确定 LLCZ 的 MIC 为所有测试病原体的 0.25mg/L。孵育开始后 6 至 48 小时内，生长受到抑制。LLCZ 抑制了黏附前阶段和晚期黏附阶段的生物膜形成。此外，单次剂量的 LLCZ 使幼虫的存活率分别提高了 40%和 20%，对 和 spp.。这是第一项证明 LLCZ 对 和 的活性的研究，也是第一项显示 LLCZ 在 spp. 中具有抗生物膜作用的研究。Scedosporium 和 Lomentospora 是机会性、多药耐药病原体，会导致免疫抑制患者和有时健康人群发生侵袭性感染。 对目前可用的抗真菌药物具有泛耐药性，这两种物种与高死亡率相关。因此，发现对这些耐药真菌具有作用的新型抗真菌药物至关重要。我们的研究表明了卢立康唑（LLCZ）对 和 spp. 的作用，以及在 感染模型中的作用。这些数据揭示了 LLCZ 对 和其在 spp. 中的抗生物膜作用的先前未知的抑制作用。它扩展了关于唑类耐药真菌的文献，并可能导致针对这些机会性真菌病原体的未来治疗策略的发展。
