Denning D W, Warn P
Hope Hospital, School of Medicine, University of Manchester, Salford M6 8HD, Manchester M8 6RB, United Kingdom.
Antimicrob Agents Chemother. 1999 Nov;43(11):2592-9. doi: 10.1128/AAC.43.11.2592.
Using an isolate of Aspergillus fumigatus that is less susceptible in vivo to amphotericin B than most other isolates, we compared different doses of liposomal nystatin (L-nystatin), liposomal amphotericin B (L-amphotericin), and amphotericin B lipid complex (ABLC) with amphotericin B deoxycholate. Four experiments with intravenously infected neutropenic mice were conducted. A dose of L-nystatin at 10 mg/kg of body weight was toxic (the mice had fits or respiratory arrest). The optimal dosage of L-nystatin was 5 mg/kg daily on days 1, 2, 4, and 7 (90% survival). This was superior to L-amphotericin (5 mg/kg [P = 0.24] and 1 mg/kg [P < 0.0001]), ABLC (5 mg/kg [P = 0.014] and 1 mg/kg [P < 0.0001]), and amphotericin B deoxycholate (5 mg/kg [P = 0.008]). In terms of liver and kidney cultures, L-nystatin (5 mg/kg) was superior to all other regimens (P = 0.0032 and <0.0001, respectively). Higher doses of L-amphotericin (25 and 50 mg/kg) in one earlier experiment were more effective (100% survival) than 1 mg of L-amphotericin per kg and amphotericin deoxycholate (5 mg/kg) in terms of mortality and both liver and kidney culture results and to L-amphotericin (5 mg/kg) in terms of liver and kidney culture results only. ABLC (25 mg/kg) given daily for 7 days was superior to ABLC (50 mg/kg [P = 0.03]) but not to ABLC at 5 mg/kg or amphotericin B deoxycholate in terms of mortality, although it was in terms of liver and kidney culture results. No dose-response for amphotericin B (5 and 1 mg/kg) was demonstrable. In conclusion, in this stringent model, high doses of L-amphotericin and ABLC could overcome reduced susceptibility to amphotericin B deoxycholate, but all were inferior to 5- to 10-fold lower doses of L-nystatin.
我们使用了一株烟曲霉分离株，该分离株在体内对两性霉素B的敏感性低于大多数其他分离株，我们将不同剂量的制霉菌素脂质体（L-制霉菌素）、两性霉素B脂质体（L-两性霉素）和两性霉素B脂质复合物（ABLC）与去氧胆酸盐两性霉素B进行了比较。对静脉感染的中性粒细胞减少小鼠进行了四项实验。10mg/kg体重的L-制霉菌素剂量有毒（小鼠出现抽搐或呼吸骤停）。L-制霉菌素的最佳剂量是在第1、2、4和7天每天5mg/kg（存活率90%）。这优于L-两性霉素（5mg/kg[P=0.24]和1mg/kg[P<0.0001]）、ABLC（5mg/kg[P=0.014]和1mg/kg[P<0.0001]）以及去氧胆酸盐两性霉素B（5mg/kg[P=0.008]）。在肝脏和肾脏培养方面，L-制霉菌素（5mg/kg）优于所有其他治疗方案（分别为P=0.0032和<0.0001）。在一项早期实验中，较高剂量的L-两性霉素（25和50mg/kg）在死亡率以及肝脏和肾脏培养结果方面比每千克1mg的L-两性霉素和去氧胆酸盐两性霉素（5mg/kg）更有效（存活率100%），仅在肝脏和肾脏培养结果方面比L-两性霉素（5mg/kg）更有效。连续7天每天给予ABLC（25mg/kg）在死亡率方面优于ABLC（50mg/kg[P=0.03]），但在死亡率方面不优于5mg/kg的ABLC或去氧胆酸盐两性霉素B，尽管在肝脏和肾脏培养结果方面是这样。未显示两性霉素B（5和1mg/kg）的剂量反应。总之，在这个严格的模型中，高剂量的L-两性霉素和ABLC可以克服对去氧胆酸盐两性霉素B敏感性降低的问题，但所有这些都不如低5至10倍剂量的L-制霉菌素。
