雾化氨基糖化物用于呼吸机相关肺炎:实验研究的方法考虑和经验教训
Jean-Jacques Rouby1, Jing Xia2, Jayesh Dhanani3,4
1Department of Anaesthesiology and Critical Care, Sorbonne University, GRC 29, Assistance Publique Hôpitaux de Paris (AP-HP), DMU DREAM, Multidisciplinary Intensive Care Unit, Pitié-Salpêtrière Hospital, Paris, France.
雾化氨基糖化物在感染的肺部达到杀菌度,挑战传统的静脉注射. 这种方法显示出治疗肺部感染的潜力,尽管人们担心系统性毒性.
科学领域:
- 药理学 药理学是指药理学的学科.
- 传染性疾病 传染性疾病
- 肺部医学 肺部医学
背景情况:
- 氨基糖化物是依赖度的杀菌抗生素.
- 静脉注射显示肺透率较低和显著的全身毒性 (脏,耳毒性).
- 由于有毒性问题,目前的指导方针限制了阿米诺糖的使用时间为5天.
研究的目的:
- 评估雾化氨基糖化物在治疗肺部感染中的疗效和药理动力学.
- 为了比较雾化与静脉注射氨基糖化物的肺透和全身毒性.
- 为了研究肺部空气和损伤对氨基糖化物分布的影响.
主要方法:
- 在麻醉,机械通风的绵羊和猪身上进行的实验研究.
- 使用高剂量的雾化氨基糖化物.
- 评估肺组织度和杀死细菌.
- 系统扩散和毒性的评估.
- 利用肺部微透析进行准确的药理动力学评估.
主要成果:
- 雾化氨基糖化物在受感染的肺膜中实现了快速和强大的细菌杀死.
- 膜-毛囊膜损伤增加了雾化氨基甘油酸的全身扩散.
- 肺气化损失降低了肺透率,但在合并地区仍然达到杀菌度.
- 肺部微透析证实了精确的肺部药物动力学评估,与表皮内液不同.
结论:
- 雾化氨基糖化物可以在感染的肺组织中达到杀菌度,即使在非空气化的区域.
- 这项研究挑战了这种假设,即雾化固有的保护系统毒性.
- 肺部微透析对于肺部感染中 nebulized 抗生素的准确药理动力学评估至关重要.
- 呼吁一个国际研究网络 (LUMINA) 进行进一步的研究,以研究在呼吸机相关的肺炎中雾化抗生素.
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