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一个基于机制的途径,用于管理高度活跃的N-菌体尾酒

Nicholas M Smith¹, Thomas D Nguyen¹, Wai Hoe Chin²

¹Division of Clinical and Translational Therapeutics, School of Pharmacy and Pharmaceutical Sciences, University at Buffalo, Buffalo, New York, NY, United States.

Frontiers in microbiology

|December 4, 2023

概括

菌体疗法显示出对抗微生物耐药性的承诺. 使用空腔纤维感染模型评估的菌体尾酒的玻尿酸剂量,与连续输注相比,显示出优异的细菌减少,指导最佳的施用策略.

科学领域:

微生物学微生物学
药理学药理学是指药理学的学科.
传染性疾病传染性疾病

背景情况:

抗菌素耐药性需要新的治疗策略.
菌体 (菌体) 治疗是一种可行的抗生素替代品.
优化菌体尾酒的配方和管理对于治疗成功至关重要.

研究的目的:

在动态剂量下研究抗伪蒙菌体的药理动力学 (PD).
为了比较玻尿酸与连续输液菌体的疗效.
开发菌体药动力学和耐药性的数学模型.

主要方法:

使用空腔纤维感染模型 (HFIM) 模拟体内药理动力学 (PK).
用菌体 LUZ19,PYO2 和 E215.5 进行外源单一治疗和组合治疗.
开发了一种基于机制的数学模型,包括菌体PD,竞争和抵抗.
进行蒙特卡洛模拟,以预测不同剂量方案下的细菌数量.

主要成果:

用LUZ19进行玻尿酸单疗法,实现了 Pseudomonas aeruginosa 的完全减少.
用LUZ19 + PYO2或LUZ19 + E215进行结合玻尿酸治疗,使细菌负载降低到<2 log10 CFU/mL.
连续输注PYO2是无效的,强调了剂量策略的重要性.

结论:

玻尿酸剂量方案对于菌体治疗的有效性优于连续输注.
试管室和体模型对于优化菌体尾酒的管理至关重要.
了解菌体PK/PD是打击抗菌素耐药性的关键.

关键词:

伪omonas aeruginosa 这种类型的病毒.空洞纤维感染模型的空洞纤维感染模型.数学建模的数学建模菌体尾酒可以使用.菌体疗法是一种菌体疗法.药理动力学是药理动力学的一个方面.药物动力学药物动力学治疗优化治疗优化

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