Antifungal prophylaxis is recommended to prevent invasive fungal disease caused by Candida spp., Aspergillus spp., and Pneumocystis jirovecii in patients at risk for opportunistic infections, such as allogeneic blood or marrow transplant recipients, patients with hematological disease undergoing chemotherapy, or patients on immunosuppressive therapies. Current approaches to antifungal prophylaxis require multiple agents to cover these key fungi. Rezafungin, a novel echinocandin designed for next-generation properties (e.g., greater stability and long-acting pharmacokinetics for once-weekly dosing), has demonstrated in vitro activity against Candida and Aspergillus spp. and efficacy against Pneumocystis spp. biofilms. Rezafungin was evaluated in in vivo studies of prophylactic efficacy using immunosuppressed mouse models of invasive candidiasis, aspergillosis, and Pneumocystis pneumonia. Rezafungin reduction of Candida CFU burden was generally greater with increasing drug concentrations (5, 10, or 20 mg/kg) and when rezafungin was administered closer to the time of fungal challenge (day −1, −3, or −5). Similarly, in the aspergillosis model, survival rates increased with drug concentrations and when rezafungin was administered closer to the time of fungal challenge. Against Pneumocystis murina, rezafungin significantly reduced trophic nuclei and asci counts at all doses tested. Rezafungin prevented infection at the two higher doses compared to vehicle and had comparable activity to the active control trimethoprim-sulfamethoxazole at human equivalent doses for prevention. These findings support phase 3 development of rezafungin and the potential for single-agent prophylaxis against invasive fungal disease caused by Candida spp., Aspergillus spp., and Pneumocystis jirovecii.

中文翻译：

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瑞扎芬净在侵袭性念珠菌病、曲霉菌病和肺孢子虫肺炎预防性小鼠模型中的功效


对于有机会性感染风险的患者，例如同种异体血液或骨髓移植受者、接受化疗的血液病患者或接受免疫抑制的患者，建议采用抗真菌预防治疗，以预防由念珠菌属、曲霉属和耶氏肺孢子菌引起的侵袭性真菌病。疗法。目前的抗真菌预防方法需要多种药物来覆盖这些关键真菌。 Rezafungin 是一种新型棘白菌素，具有下一代特性（例如每周一次给药的更高稳定性和长效药代动力学），已证明具有针对念珠菌和曲霉属的体外活性。以及对肺孢子菌的功效。生物膜。使用侵袭性念珠菌病、曲霉病和肺孢子虫肺炎的免疫抑制小鼠模型，在体内研究中评估了雷扎芬净的预防功效。随着药物浓度（5、10或20 mg/kg）的增加以及当雷扎芬净在接近真菌攻击时间（第-1、-3或-5天）施用时，雷扎芬净对念珠菌CFU负荷的降低通常更大。类似地，在曲霉病模型中，存活率随着药物浓度的增加以及在接近真菌攻击时间时施用雷扎芬净而增加。针对鼠肺孢子虫，雷扎芬净在所有测试剂量下均显着减少营养核和子囊计数。与媒介物相比，雷扎芬净以两个较高剂量预防感染，并且在人类等效剂量下具有与活性对照甲氧苄啶-磺胺甲恶唑相当的预防活性。 这些发现支持雷扎芬净的 3 期开发以及单药预防由念珠菌属、曲霉属和耶氏肺孢子菌引起的侵袭性真菌病的潜力。