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脂质体抗生素疗法在大鼠大肠杆菌腹膜炎输注模型中的疗效

Efficacy of liposomal antibiotic therapy in a rat infusion model of Escherichia coli peritonitis.

作者信息

Martineau L, Shek P N

机构信息

Operational Medicine Sector, Defence and Civil Institute of Environmental Medicine, West Toronto, ON, Canada.

出版信息

Crit Care Med. 1999 Jun;27(6):1153-8. doi: 10.1097/00003246-199906000-00041.

DOI:10.1097/00003246-199906000-00041
PMID:10397221
Abstract

OBJECTIVE

To compare the potential therapeutic effect of liposomal vs. free cefoxitin.

DESIGN

Randomized, controlled study, using a rat model of peritonitis.

SETTING

Government research facility.

SUBJECTS

Male Sprague-Dawley rats.

INTERVENTIONS

Rats were infused intraperitoneally with 6.5 x 10(8) colony forming units of Escherichia coli over 12 hrs. Animals were then randomized to receive intravenous saline, free cefoxitin, liposomal cefoxitin, or plain liposomes twice daily until they were killed.

MEASUREMENTS AND MAIN RESULTS

Free cefoxitin significantly reduced the number of E. coli after 24 hrs compared with saline treatment in both liver and spleen. However, liposomal cefoxitin further decreased the bacterial content by five-fold to ten-fold in these organs. Minimal bactericidal effect was observed in animals injected with plain liposomes. Although administration of liposomal cefoxitin for 7 days further reduced bacterial counts in liver and spleen, there was no apparent beneficial bactericidal effect of free cefoxitin over saline at 7 days. There was approximately a ten-fold reduction in bacterial content in the lungs after 24 hrs in all three treatments, but no further reduction was observed after 7 days. There was no difference in 7-day survival rate in animals treated with plain liposomes or saline (45% vs. 39%). Although survival tended to increase with free cefoxitin treatment (64%), this outcome was significantly improved with the use of liposomal cefoxitin (82%).

CONCLUSIONS

Liposomal cefoxitin enhanced bacterial killing in liver and spleen in this model of E. coli peritonitis. It also improved survival outcome relative to no treatment but not compared with free cefoxitin.

摘要

目的

比较脂质体头孢西丁与游离头孢西丁的潜在治疗效果。

设计

采用大鼠腹膜炎模型进行随机对照研究。

地点

政府研究机构。

研究对象

雄性斯普拉格 - 道利大鼠。

干预措施

大鼠在12小时内腹腔注射6.5×10⁸个大肠杆菌菌落形成单位。然后将动物随机分组,每天两次静脉注射生理盐水、游离头孢西丁、脂质体头孢西丁或普通脂质体,直至处死。

测量指标及主要结果

与生理盐水治疗相比,游离头孢西丁在24小时后显著降低了肝脏和脾脏中的大肠杆菌数量。然而,脂质体头孢西丁使这些器官中的细菌含量进一步降低了五倍至十倍。在注射普通脂质体的动物中观察到最小杀菌效果。虽然脂质体头孢西丁给药7天进一步降低了肝脏和脾脏中的细菌数量,但在7天时游离头孢西丁相对于生理盐水没有明显的有益杀菌效果。在所有三种治疗中,24小时后肺部细菌含量均降低了约十倍,但7天后未观察到进一步降低。接受普通脂质体或生理盐水治疗的动物7天生存率无差异(45%对39%)。虽然游离头孢西丁治疗的生存率有上升趋势(64%),但使用脂质体头孢西丁可显著提高生存率(82%)。

结论

在该大肠杆菌腹膜炎模型中,脂质体头孢西丁增强了肝脏和脾脏中的细菌杀灭作用。与未治疗相比,它还改善了生存结果,但与游离头孢西丁相比无差异。

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