Single-dose AmBisome (liposomal amphotericin B) as prophylaxis for murine systemic candidiasis and histoplasmosis
Single-dose AmBisome (liposomal amphotericin B) as prophylaxis for murine systemic candidiasis and histoplasmosis
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DOI：
10.1128/aac.44.9.2327-2332.2000
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发表时间：
2000-09-01
影响因子：
4.9
通讯作者：
Proffitt, RT
中科院分区：
文献类型：
--
作者：
Garcia, A;Adler-Moore, JP;Proffitt, RT
AmBisome是一种脂质体制剂，具有广谱抗真菌活性，与母体药物相比毒性大大降低。在这项研究中，在免疫活性和免疫抑制的C57 BL/6小鼠中测试了白念珠菌或荚膜组织胞浆菌激发的单剂量预防剂--阿替西霉素B脱氧胆酸盐（Fungizone）（1 mg/kg）和AmBisome（1 - 20 mg/kg）。预防效果基于存活率和靶器官（肾脏或脾脏）中的真菌负荷。在组织胞浆菌攻击后9至10天，对照组和Fungizone组中80%至90%的免疫活性小鼠和免疫抑制小鼠死亡。所有AmBisome处理的小鼠均存活，尽管在给予lmg/kg的AmBisome组中，小鼠在第10至12天变得濒死。在给予10或20 mg/kg的AmBisome的组织胞浆菌攻击的小鼠中未检测到脾CFU。到组织胞浆菌攻击后23至24天，除了接受20 mg AmBisome/kg的4只小鼠外，所有免疫抑制小鼠均发生真菌生长和/或死亡。在给予10或20 mg AmBisome/kg的免疫活性小鼠的脾脏中仍然没有可检测到的真菌。在C.在攻击后7天的白色念珠菌实验中，未处理组和处理组中的所有动物均存活，具有培养阳性的肾脏。给予5至20 mg/kg的AmBisome组的肾脏真菌负荷比Fungizone组中的那些低至少1个对数单位，并且显著低于未处理的对照组中的那些（P <0.05）。随着AmBisome剂量的增加，肾脏中真菌生长有减少的趋势。总之，这些结果表明单次高剂量的AmBisome（5至20 mg/kg）在免疫活性和免疫抑制的鼠H. capsulatum和C.白色念珠菌模型。
AmBisome is a liposomal formulation of amphotericin B that has broad-spectrum antifungal activity and greatly reduced toxicity compared to the parent drug. In this study, amphotericin B deoxycholate (Fungizone) (1 mg/kg) and AmBisome (1 to 20 mg/kg) were tested as single-dose prophylactic agents in both immunocompetent and immunosuppressed C57BL/6 mice challenged with either Candida albicans or Histoplasma capsulatum. Prophylactic efficacy was based on survival and fungal burden in the target organ (kidneys or spleen). At 9 to 10 days after histoplasma challenge, 80 to 90% of both immunocompetent and immunosuppressed mice in the control and Fungizone groups had died. All AmBisome-treated mice survived, although in the AmBisome groups given 1 mg/kg, the mice became moribund by day 10 to 12, No spleen CFU were detected in the histoplasma-challenged mice given 10 or 20 mg of AmBisome per kg. By 23 to 24 days after histoplasma challenge, fungal growth and/or death had occurred in all immunosuppressed mice except for four mice receiving 20 mg of AmBisome per kg. There were still no detectable fungi in the spleens of immunocompetent mice given 10 or 20 mg of AmBisome per kg. In the C. albicans experiment at 7 days postchallenge, all animals in both untreated and treated groups were alive with culture-positive kidneys. The kidney fungal burdens in AmBisome groups given 5 to 20 mg/kg were at least 1 log unit lower than those in the Fungizone group and significantly lower than those in the untreated control group (P < 0,05). There was a trend toward decreasing fungal growth in the kidneys as the dose of AmBisome was increased. In conclusion, these results show that a single high dose of AmBisome (5 to 20 mg/kg) had prophylactic efficacy in immunocompetent and immunosuppressed murine H. capsulatum and C. albicans models.