关键词: Animal model Antifungal therapy Infección sistémica Modelo animal Saccharomyces cerevisiae Sensibilidad Susceptibility Systemic infection Tratamiento antifúngico

Mesh : Amphotericin B / pharmacology therapeutic use Animals Antifungal Agents / pharmacology therapeutic use Disease Models, Animal Echinocandins / pharmacology therapeutic use Humans Male Mice Microbial Sensitivity Tests Mycoses / drug therapy Saccharomyces cerevisiae / drug effects Voriconazole / pharmacology therapeutic use

来  源:   DOI:10.1016/j.riam.2018.04.004   PDF(Sci-hub)

Abstract:
BACKGROUND: The incidence of systemic infections by Saccharomyces cerevisiae has increased in recent years, especially among immunocompromised patients. Amphotericin B, voriconazole or echinocandins have been used with favorable outcome against systemic infections by this fungus. However, clinical experience is limited and no in vivo studies have been conducted.
OBJECTIVE: We evaluated the in vitro activity of nine antifungal compounds against S.cerevisiae and the in vivo efficacy of those three antifungals showing the highest in vitro activity by using a murine model of systemic infection.
METHODS: Minimal inhibitory concentrations (MICs) were determined by the microdilution method against three strains of S. cerevisiae. After intravenous infection with 5×107 CFUs, animals received liposomal amphotericin B (5mg/kg), voriconazole (25mg/kg) or anidulafungin (5mg/kg). Treatment efficacy was assessed by determining of CFUs/g in liver, kidney, brain, lung and spleen.
RESULTS: 5-Fluorocytosine was the most in vitro active compound followed by amphotericin B, voriconazole and anidulafungin. The in vivo study showed that liposomal amphotericin B was the most effective drug driving highest fungal clearance.
CONCLUSIONS: All treatments reduced the fungal load in comparison to the control group, being liposomal amphotericin B the most effective drug followed by anidulafungin and finally voriconazole.
摘要:
背景:近年来,酿酒酵母全身感染的发生率有所增加,尤其是在免疫功能低下的患者中。两性霉素B,伏立康唑或棘白菌素已被用于对抗这种真菌的全身性感染。然而,临床经验有限,尚未进行体内研究。
目的:我们使用小鼠全身感染模型评估了9种抗真菌化合物对酿酒酵母的体外活性以及显示出最高体外活性的这3种抗真菌药物的体内功效。
方法:通过微量稀释法测定三种酿酒酵母菌株的最小抑制浓度(MIC)。5×107CFU静脉感染后,动物接受脂质体两性霉素B(5mg/kg),伏立康唑(25mg/kg)或anidulafungin(5mg/kg)。通过确定肝脏中的CFU/g来评估治疗效果。肾,大脑,肺和脾。
结果:5-氟胞嘧啶是体外活性最高的化合物,其次是两性霉素B,伏立康唑和Anidulafungin.体内研究表明,脂质体两性霉素B是驱动真菌清除率最高的最有效药物。
结论:与对照组相比,所有治疗均降低了真菌负荷,脂质体两性霉素B是最有效的药物,其次是阿尼达芬净,最后是伏立康唑。
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