Efficacy of caspofungin alone and in combination with voriconazole in a guinea pig model of invasive aspergillosis
Efficacy of caspofungin alone and in combination with voriconazole in a guinea pig model of invasive aspergillosis
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DOI：
10.1128/aac.46.8.2564-2568.2002
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发表时间：
2002-08-01
影响因子：
4.9
通讯作者：
Patterson, TF
中科院分区：
文献类型：
--
作者：
Kirkpatrick, WR;Perea, S;Patterson, TF
在免疫抑制的暂时性低血糖豚鼠侵袭性曲霉病模型中，评价了醋酸卡泊芬净（CAS）单独使用和与伏立康唑（VRC）联合使用的抗真菌活性。在用烟曲霉进行致死性静脉内攻击前4天开始，用20 mg/kg体重/天的曲安西龙皮下抑制豚鼠的免疫，并用150 mg/kg环磷酰胺腹膜内（i. p.）攻毒前1天。激发后24小时开始腹腔注射1和2.5 mg/kg/天CAS（联合或不联合口服5 mg/kg/天VRC）、口服5 mg/kg/天VRC或腹腔注射1.25 mg/kg/天两性霉素B（AMB）治疗，并持续5天。12只未给药对照组豚鼠中有12只死亡，而1和2.5 mg/kg/天CAS给药组豚鼠中分别有4只和6只死亡，AMB给药组豚鼠中有3只死亡。在接受1 mg/kg/天CAS +5 mg/kg/天VRC、2.5 mg/kg/天CAS +5 mg/kg/天VRC或5 mg/kg/天VRC单独给药的动物中未发生死亡。与对照组相比，两种CAS方案均延长了存活时间，降低了组织中的殖民地计数。与对照组相比，VRC和AMB处理显著降低了所选动物组织中的殖民地计数。与CAS处理的动物组织相比，VRC和AMB处理也导致组织中的菌落计数减少（差异无统计学显著性），并改善了存活时间，但没有使组织灭菌。与对照组相比，CAS + VRC联合治疗使组织中的菌落计数减少了1,000倍，并且是唯一显著减少阳性培养物数量的方案。CAS加VRC的组合在该模型中是高度有效的，并且应该进一步评估用于对抗侵袭性曲霉病。
The antifungal activity of caspofungin acetate (CAS) alone and in combination with voriconazole (VRC) was evaluated in an immunosuppressed transiently neutropenic guinea pig model of invasive aspergillosis. Guinea pigs were immunosuppressed with triamcinolone at 20 mg/kg of body weight/day subcutaneously beginning 4 days prior to lethal intravenous challenge with Aspergillus fumigatus and were made temporarily neutropenic with cyclophosphamide administered at 150 mg/kg intraperitoneally (i.p.) 1 day prior to challenge. Therapy with i.p. CAS at 1 and 2.5 mg/kg/day (with and without oral VRC at 5 mg/kg/day), oral VRC at 5 mg/kg/day, or i.p. amphotericin B (AMB) at 1.25 mg/kg/day was begun 24 h after challenge and was continued for 5 days. Mortality occurred in 12 of 12 untreated controls, whereas mortality occurred in 4 of 12 and 6 of 12 guinea pigs treated with CAS at 1 and 2.5 mg/kg/day, respectively, and in 3 of 12 guinea pigs treated with AMB. No mortality occurred among animals treated with CAS at 1 mg/kg/day plus VRC at 5 mg/kg/day, CAS at 2.5 mg/kg/day plus VRC at 5 mg/kg/day, or VRC at 5 mg/kg/day alone. Both CAS regimens increased the survival times and reduced the colony counts in tissue compared with those for the controls. Treatment with VRC and AMB significantly reduced the colony counts in the tissues of selected animals compared with those in the tissues of the controls. Treatment with VRC and AMB also resulted in reductions in colony counts in tissues compared with those in the tissues of animals treated with CAS (the difference was not statistically significant) and improved the survival times but did not sterilize tissues. Combination therapies with CAS plus VRC at either dose reduced colony counts in tissues 1,000-fold over those for the controls and were the only regimens that significantly reduced the numbers of positive cultures. The combinations of CAS plus VRC were highly effective in this model and should be further evaluated for use against invasive aspergillosis.