Leenders A C, de Marie S, ten Kate M T, Bakker-Woudenberg I A, Verbrugh H A
Department of Bacteriology, University Hospital Rotterdam-Dijkzigt, The Netherlands.
J Antimicrob Chemother. 1996 Aug;38(2):215-25. doi: 10.1093/jac/38.2.215.
The efficacy of AmBisome, a liposomal formulation of amphotericin B, was compared with that of Fungizone (amphotericin B desoxycholate), in a rat model of unilateral, pulmonary aspergillosis. Repeated administration of cyclophosphamide resulted in persistent, severe granulocytopenia. The left lung was inoculated with a conidial suspension of Aspergillus fumigatus, thus establishing an unilateral infection. Antifungal treatment was started 40 h after fungal inoculation, at which time mycelial disease was confirmed by histological examination. Both Fungizone 1 mg/kg and AmBisome 10 mg/kg resulted in increased survival in terms of delayed as well as reduced mortality. Quantitative cultures of lung tissue showed that only AmBisome 10 mg/kg resulted in reduction of the number of fungal cfus in the inoculated left lung. Compared with Fungizone, both AmBisome 1 mg/kg/day and AmBisome 10 mg/kg/day significantly prevented dissemination from the infected left lung to the right lung. In addition, both AmBisome regimens reduced hepatosplenic dissemination, and the 10 m/kg dosage fully prevented this complication. In conclusion, when compared with Fungizone, in this model AmBisome is more effective in reducing dissemination of unilateral, pulmonary aspergillosis, even when given in relatively low dosage. Such low dosages may have a place in prophylactic settings.
在单侧肺曲霉病大鼠模型中,对两性霉素B的脂质体制剂安必素(AmBisome)与两性霉素B去氧胆酸盐(Fungizone)的疗效进行了比较。反复给予环磷酰胺导致持续性严重粒细胞减少。将烟曲霉分生孢子悬液接种到左肺,从而建立单侧感染。在真菌接种后40小时开始抗真菌治疗,此时通过组织学检查确认存在菌丝体疾病。Fungizone 1mg/kg和安必素10mg/kg均使延迟死亡率降低且总死亡率下降,从而提高了生存率。肺组织定量培养显示,只有安必素10mg/kg能使接种的左肺中真菌集落形成单位数量减少。与Fungizone相比,安必素1mg/kg/天和安必素10mg/kg/天均能显著防止感染从左肺扩散至右肺。此外,两种安必素给药方案均减少了肝脾扩散,10mg/kg剂量完全预防了这一并发症。总之,在该模型中,与Fungizone相比,安必素在减少单侧肺曲霉病扩散方面更有效,即使给予相对低剂量时也是如此。这种低剂量可能在预防方面具有应用价值。