Department of Pathology and Laboratory Medicine, Fungus Testing Laboratory, University of Texas Health Science Center at San Antonio, San Antonio, Texas, USA.
Department of Medicine, Division of Infectious Diseases, University of Texas Health Science Center at San Antonio, San Antonio, Texas, USA.
Microbiol Spectr. 2024 Oct 3;12(10):e0135624. doi: 10.1128/spectrum.01356-24. Epub 2024 Aug 20.
We evaluated the activity of nikkomycin Z against central nervous system coccidioidomycosis. Mice were inoculated intracranially with arthroconidia of , and treatment with nikkomycin Z (50, 100, or 300 mg/kg orally TID) or fluconazole (25 mg/kg orally BID) began 2 days later. Each dose of nikkomycin Z and fluconazole significantly improved survival and reduced brain fungal burden compared with vehicle control. Further studies of nikkomycin Z against coccidioidomycosis are warranted.
species are endemic fungi that are capable of causing disease in patients with various comorbidities, as well as in otherwise healthy individuals. Treatment options for coccidioidomycosis are suboptimal, as azole antifungals may be limited by drug interactions and adverse effects due to interactions with enzymes found in humans and other mammals. Nikkomycin Z is an investigational agent that works against a target specific to the fungal cell wall (chitin), which is not present in the cells of humans or other mammals. In this study, we show that frequent oral administration of nikkomycin Z is effective in an experimental model of central nervous system coccidioidomycosis. Further studies of nikkomycin Z against coccidioidomycosis may be warranted.
我们评估了 nikkomycin Z 对中枢神经系统球孢子菌病的活性。将 arthroconidia of 颅内接种到小鼠中，并且在 2 天后开始用 nikkomycin Z（50、100 或 300 mg/kg 口服 TID）或氟康唑（25 mg/kg 口服 BID）进行治疗。与载体对照相比，每种剂量的 nikkomycin Z 和氟康唑都显著提高了存活率并降低了脑部真菌负荷。需要进一步研究 nikkomycin Z 对球孢子菌病的作用。
种是地方性真菌，能够使患有各种合并症的患者以及健康个体患病。球孢子菌病的治疗选择并不理想，因为唑类抗真菌药可能由于与人类和其他哺乳动物中发现的酶相互作用而受到药物相互作用和不良反应的限制。Nikkomycin Z 是一种针对真菌细胞壁（几丁质）的靶标特异性的研究性药物，而几丁质不存在于人类或其他哺乳动物的细胞中。在这项研究中，我们表明，频繁口服 nikkomycin Z 在中枢神经系统球孢子菌病的实验模型中是有效的。需要进一步研究 nikkomycin Z 对球孢子菌病的作用。
