Efficacy of liposomal gentamicin against Rhodococcus equi in a mouse infection model and colocalization with R. equi in equine alveolar macrophages
Efficacy of liposomal gentamicin against Rhodococcus equi in a mouse infection model and colocalization with R. equi in equine alveolar macrophages
复制标题
DOI：
10.1016/j.vetmic.2015.01.015
复制
发表时间：
2015-04-17
影响因子：
3.3
通讯作者：
Arnold, Robert D.
中科院分区：
文献类型：
--
作者：
Burton, Alexandra J.;Giguere, Steeve;Arnold, Robert D.
马红球菌是一种兼性胞内病原菌，是马驹肺炎的重要病因，在体外对庆大霉素的杀灭作用高度敏感。然而，庆大霉素在体内是无效的，由于其差的细胞渗透。药物在脂质体中的包封增强了细胞摄取。本研究的目的是比较庆大霉素脂质体和游离庆大霉素对马巨噬细胞的摄取以及与R.比较庆大霉素脂质体、游离庆大霉素和克拉霉素与利福平联合应用对降低R.在感染的小鼠模型中的马CFU。离体暴露后，含有庆大霉素脂质体（91.9 +/- 7.6%）的马肺泡巨噬细胞的平均（+/- SD）百分比显著高于游离庆大霉素（16.8 +/- 12.5%）。细胞内药物和R.通过共聚焦显微镜评估，与暴露于游离庆大霉素的细胞（10.4 +/- 8.7%）相比，暴露于庆大霉素脂质体的细胞（81.2 +/- 17.8%）中发生Equi的比例显著更高。R.与用游离庆大霉素处理的小鼠或未处理的对照小鼠相比，用庆大霉素脂质体处理的小鼠脾脏中的马CFU显著更低。用庆大霉素脂质体治疗也导致R数量显著减少。与克拉霉素与利福平联合治疗相比，肝脏中的equi CFU。这些结果支持进一步研究庆大霉素脂质体作为一种新的治疗由R。等。(C)2015 Elsevier B. V.版权所有。
Rhodococcus equi, a facultative intracellular pathogen and an important cause of pneumonia in foals, is highly susceptible to killing by gentamicin in vitro. However, gentamicin is not effective in vivo, due to its poor cellular penetration. Encapsulation of drugs in liposomes enhances cellular uptake. The objectives of this study were to compare liposomal gentamicin and free gentamicin with respect to their uptake by equine macrophages and intracellular colocalization with R. equi and to compare the efficacies of liposomal gentamicin, free gentamicin and clarithromycin with rifampin for the reduction of R. equi CFU in a mouse model of infection. After ex vivo exposure, a significantly higher mean (+/- SD) percentage of equine alveolar macrophages contained liposomal gentamicin (91.9 +/- 7.6%) as opposed to free gentamicin (16.8 +/- 12.5%). Intracellular colocalization of drug and R. equi, as assessed by confocal microscopy, occurred in a significantly higher proportion of cells exposed to liposomal gentamicin (81.2 +/- 17.8%) compared to those exposed to free gentamicin (10.4 +/- 8.7%). The number of R. equi CFU in the spleen was significantly lower in mice treated with liposomal gentamicin compared to that of mice treated with free gentamicin or to untreated control mice. Treatment with liposomal gentamicin also resulted in a significantly greater reduction in the number of R. equi CFU in the liver compared to treatment with clarithromycin in combination with rifampin. These results support further investigation of liposomal gentamicin as a new treatment for infections caused by R. equi. (C) 2015 Elsevier B.V. All rights reserved.