Kashimoto Shigeki, Takemoto Koji, Yamamoto Yutaka, Kanazawa Katsunori
Pharmacology Research Laboratories, Dainippon Sumitomo Pharma Co., Ltd.
Jpn J Antibiot. 2010 Jun;63(3):265-72.
This study evaluated the in vivo activity of liposomal amphotericin B (L-AMB) and deoxycholate amphotericin B (D-AMB) in a murine model of disseminated infection caused by Exophiala dermatitidis. Cyclophosphamide-treated neutropenic ddY mice were inoculated intravenously with conidial suspensions of E. dermatitidis IFM 4827 or IFM 53409. The maximum tolerated doses of L-AMB and D-AMB were set at 10 mg/kg and 1 mg/kg, respectively. Four hours after infection, a single dose of L-AMB (0.3 to 10 mg/kg) or D-AMB (0.1 to 1 mg/kg) was administered intravenously. The efficacy of the antifungal treatment was assessed by the survival time over two weeks and the tissue fungal burdens 4 days after infection. L-AMB at a dose of > or =1 mg/kg significantly prolonged the survival time of mice infected with either strain compared with that of the control group. Percent survivals in the 10 mg/kg L-AMB-treated group (100% and 75%) were higher than those in the 1 mg/kg D-AMB-treated group (20% and 37.5%) in the IFM 4827 and IFM 53409 models, respectively. In the IFM 4827 model, 10 mg/kg L-AMB exhibited greater efficacy than 1 mg/kg D-AMB in terms of reducing the tissue fungal burdens (blood, lung, liver, spleen, and kidneys). These findings suggest that L-AMB was effective in the treatment of experimental disseminated E. dermatitidis infection, and the efficacy of L-AMB was superior to that of D-AMB.
本研究在由皮炎外瓶霉引起的播散性感染小鼠模型中评估了两性霉素B脂质体(L-AMB)和去氧胆酸盐两性霉素B(D-AMB)的体内活性。用环磷酰胺处理造成中性粒细胞减少的ddY小鼠,经静脉接种皮炎外瓶霉IFM 4827或IFM 53409的分生孢子悬浮液。L-AMB和D-AMB的最大耐受剂量分别设定为10mg/kg和1mg/kg。感染后4小时,经静脉给予单剂量的L-AMB(0.3至10mg/kg)或D-AMB(0.1至1mg/kg)。通过两周以上的生存时间和感染后4天的组织真菌负荷来评估抗真菌治疗的疗效。与对照组相比,剂量≥1mg/kg的L-AMB显著延长了感染任一菌株小鼠的生存时间。在IFM 4827和IFM 53409模型中,10mg/kg L-AMB治疗组的生存率(分别为100%和75%)高于1mg/kg D-AMB治疗组(分别为20%和37.5%)。在IFM 4827模型中,就降低组织真菌负荷(血液、肺、肝、脾和肾)而言,10mg/kg L-AMB比1mg/kg D-AMB表现出更强的疗效。这些发现表明,L-AMB在治疗实验性播散性皮炎外瓶霉感染中有效,且L-AMB的疗效优于D-AMB。