Efficacy of intravenous liposomal amphotericin B (AmBisome) against coccidioidal meningitis in rabbits

Efficacy of intravenous liposomal amphotericin B (AmBisome) against coccidioidal meningitis in rabbits
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DOI:
10.1128/aac.46.8.2420-2426.2002
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发表时间:
2002-08-01
影响因子:
4.9
通讯作者:
Stevens, DA
Stevens, DA
中科院分区:
医学2区
文献类型:
--
作者:
Clemons, KV;Sobel, RA;Stevens, DA

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将静脉注射脂质体两性霉素B(AmBisome[AmBi])治疗实验性球孢子菌性脑膜炎的疗效与口服氟康唑(FLC)和静脉注射常规两性霉素B(AMB)的疗效进行了比较。雄性新西兰白兔通过脑池内接种粗球孢子菌的关节孢子而感染。感染后5天开始,动物接受以下处理之一:5%葡萄糖水稀释剂;按1mg/kg体重给予AMB;按7.5、15或22.5mg/kg静脉注射AmBi,每周3次,持续3周;或按80mg/kg口服FLC,持续19天。治疗停止1周后,对所有存活的动物实施安乐死,测定脊髓和大脑中剩余的菌落形成单位(CFU)数量,并进行组织学分析。与对照组相比,所有接受AmBi、FLC或AMB治疗的动物均存活且存活时间延长(P<0.05)。在脊髓和大脑中,接受AmBi治疗的动物的CFU数量显著低于接受AMB或FLC治疗的动物(P<0.05)。组织学分析显示,接受AmBi治疗的动物的炎症反应最轻,接受FLC治疗的动物的炎症反应最严重。这些结果表明,AmBi在治疗实验性球孢子菌性脑膜炎方面比AMB或FLC更有效。
The efficacy of intravenously administered liposomal amphotericin B (AmBisome [AmBi]) for the treatment of experimental coccidioidal meningitis was compared with those of oral fluconazole (FLC) and intravenously administered conventional amphotericin B (AMB). Male New Zealand White rabbits were infected by intracisternal inoculation of artbroconidia of Coccidioides immitis. Starting 5 days postinfection, animals received one of the following: 5% dextrose water diluent; AMB given at 1 mg/kg of body weight; AmBi given at 7.5, 15, or 22.5 mg/kg intravenously three times per week for 3 weeks; or oral FLC given at 80 mg/kg for 19 days. One week after the cessation of therapy, all survivors were euthanatized, the numbers of CFU remaining in the spinal cord and brain were determined, and histological analyses were performed. All AmBi-, FLC-, or AMB-treated animals survived and had prolonged lengths of survival compared with those for the controls (P