Fierer J, Hatlen L, Lin J P, Estrella D, Mihalko P, Yau-Young A
Department of Medicine and Pathology, Veterans Administration Medical Center, San Diego, California.
Antimicrob Agents Chemother. 1990 Feb;34(2):343-8. doi: 10.1128/AAC.34.2.343.
Gentamicin entrapped within stable multilamellar liposomes was used to treat mice after they were infected per os with Salmonella dublin. Of 10 mice, 8 survived after a single intravenous (i.v.) injection of 2 mg of gentamicin liposomes per kg compared with 0 of 10 treated with the same amount of free gentamicin. All mice survived after treatment with a single i.v. or intraperitoneal injection of 20 mg of gentamicin liposomes per kg, whereas that dose of free drug was completely ineffective and caused neuromuscular paralysis when injected rapidly i.v. In mice treated with gentamicin liposomes, there was a steady decrease in the number of salmonellae in spleens for 2 weeks after treatment. High concentrations of gentamicin were present in the spleen for at least 10 days after treatment. Although gentamicin was not detected in the mesenteric lymph nodes of mice treated with gentamicin liposomes, bacterial counts in the nodes also decreased over time. Small numbers of bacteria remained viable in the mesenteric lymph nodes and Peyer's patches but not in the spleens of mice treated with 20 to 80 mg/kg. Mice treated with doses of gentamicin liposomes as high as 80 mg/kg showed only a transient increase in blood urea nitrogen and no rise in serum creatinine. These results confirm that gentamicin in liposomes is less toxic in mice than is free gentamicin and is extremely effective therapy for disseminated Salmonella infections in mice.
将包裹在稳定多层脂质体中的庆大霉素用于经口感染都柏林沙门氏菌后的小鼠治疗。10只小鼠中，每千克体重单次静脉注射2毫克庆大霉素脂质体后，有8只存活，而用相同剂量游离庆大霉素治疗的10只小鼠全部死亡。每千克体重单次静脉注射或腹腔注射20毫克庆大霉素脂质体后，所有小鼠均存活，而该剂量的游离药物完全无效，快速静脉注射时会导致神经肌肉麻痹。在用庆大霉素脂质体治疗的小鼠中，治疗后2周脾脏中的沙门氏菌数量持续减少。治疗后至少10天，脾脏中存在高浓度的庆大霉素。尽管在用庆大霉素脂质体治疗的小鼠的肠系膜淋巴结中未检测到庆大霉素，但淋巴结中的细菌计数也随时间减少。在肠系膜淋巴结和派伊尔结中仍有少量细菌存活，但在用20至80毫克/千克治疗的小鼠脾脏中则没有。用高达80毫克/千克剂量的庆大霉素脂质体治疗的小鼠仅出现血尿素氮短暂升高，血清肌酐未升高。这些结果证实，脂质体中的庆大霉素在小鼠中的毒性低于游离庆大霉素，是治疗小鼠播散性沙门氏菌感染的极其有效的疗法。
