Pfaller Michael A
Section of Medical Microbiology, Department of Pathology, University of Iowa College of Medicine, Iowa City, Iowa 52242, USA.
Expert Opin Investig Drugs. 2004 Sep;13(9):1183-97. doi: 10.1517/13543784.13.9.1183.
Anidulafungin (LY-303366, V-echinocandin trade mark, Vicuron Pharmaceuticals, Inc.) is a new echinocandin antifungal agent with broad spectrum activity against Candida and Aspergillus spp. Anidulafungin exhibits low toxicity, concentration-dependent fungicidal activity for Candida, and a prolonged post antifungal effect (> 12h). In vitro activity demonstrates excellent potency and spectrum versus azole-susceptible and -resistant Candida spp. and a low minimum effective concentration for Aspergillus spp. In vivo anidulafungin is fungicidal against Candida in neutropenic animal models of disseminated candidiasis. Against Candida anidulafungin exhibits concentration-dependent killing and clearance of residual fungal burden in target organs (liver, lung, spleen, kidney) and plasma/tissue concentrations exceed the minimum inhibitory and minimum fungicidal concentrations of the infecting organism throughout the dosing interval. Although the activity of anidulafungin in animal models of pulmonary or disseminated aspergillosis shows increased survival and improvement in the pulmonary infarct score, the effect on residual fungal burden and Aspergillus antigenemia determination does not indicate in vivo fungicidal activity. It seems that the major effect of anidulafungin and other echinocandins in vivo against Aspergillus spp. is the decrease in the angioinvasive potential of the organisms. Clinically, anidulafungin has been shown to be safe and effective in the treatment of oesophageal candidiasis and candidemia. Further clinical application of this new antifungal agent is warranted.
阿尼芬净(LY - 303366,商品名V - echinocandin,Vicuron制药公司)是一种新型棘白菌素类抗真菌药物,对念珠菌属和曲霉属具有广谱活性。阿尼芬净毒性低,对念珠菌具有浓度依赖性杀菌活性,且抗真菌后效应延长(>12小时)。体外活性研究表明,其对唑类敏感和耐药的念珠菌属均具有优异的效力和抗菌谱,对曲霉属的最低有效浓度较低。在体内,阿尼芬净在中性粒细胞减少的播散性念珠菌病动物模型中对念珠菌具有杀菌作用。针对念珠菌,阿尼芬净表现出浓度依赖性杀菌作用,并能清除靶器官(肝脏、肺、脾脏、肾脏)中的残余真菌负荷,在整个给药间隔期间,血浆/组织浓度均超过感染病原体的最低抑菌浓度和最低杀菌浓度。尽管阿尼芬净在肺部或播散性曲霉病动物模型中的活性显示可提高生存率并改善肺部梗死评分,但对残余真菌负荷和曲霉抗原血症测定的影响并不表明其在体内具有杀菌活性。似乎阿尼芬净和其他棘白菌素类药物在体内对曲霉属的主要作用是降低病原体的血管侵袭潜力。临床上,阿尼芬净已被证明在治疗食管念珠菌病和念珠菌血症方面安全有效。这种新型抗真菌药物值得进一步临床应用。