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针对多药耐药的Acinetobacter baumannii的聚氨酸 - 里法辛组合疗法的基于模型的剂量优化

Jinxin Zhao¹, Yan Zhu¹, Mei-Ling Han¹

¹Monash Biomedicine Discovery Institute, Infection Program and Department of Microbiology, Monash University, Clayton, Victoria, Australia.

International journal of antimicrobial agents

|June 28, 2023

概括

聚氨酸B和利芬素的组合显示出协同杀死多药耐药 (MDR) Acinetobacter baumannii的作用. 这种组合疗法是治疗MDR细菌感染的有希望的选择.

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 (AMR) 是一个重大的全球健康威胁.
有限的抗生素管道需要新的治疗策略,如组合疗法.
多药耐药性 (MDR) Acinetobacter baumannii 在临床环境中构成了关键的挑战.

研究的目的:

调查聚米辛B和利芬素对MDR Acinetobacter baumannii的协同抗菌活性.
阐明观察到的协同效应背后的机制.
用药理动力学/药理动力学 (PK/PD) 建模和体内感染模型来评估组合的治疗潜力.

主要方法:

实验室杀时试验是在48小时内对三种MDR A. baumannii分离物进行的.
进行了膜完整性测试,以了解协同机制.
开发了一种半机械的PK/PD模型来描述细菌的杀死和再生.
在体内有效性被评估在一个中性贫乏的小鼠大腿感染模型.

主要成果:

聚米辛B和利芬单一疗法显示了最初的杀死,但随后出现了显著的细菌再生.
组合疗法证明了协同杀死,减少细菌负载在48小时内低于量化极限.
聚胺诱导的外膜透增强了利芬素的吸收,有助于协同作用.
通过PK/PD建模和体内研究,证实了该组合对A. baumannii的治疗潜力和疗效.

结论:

聚米辛B和利芬素联合治疗对MDR A. baumannii. 呈现强烈的协同活性.
这种组合是治疗由这些具有挑战性的病原体引起的血液和组织感染的有希望的策略.
需要对polymyxin B和rifampicin联合治疗进行临床评估.

关键词:

基于模型的剂量优化.多种药物耐药的 Acinetobacter baumannii 是一个多种药物耐药的细菌.药理动力学/药理动力学波利米克辛 (Polymyxin) 是一种多重的药物.里法皮辛 (Rifampicin) 是一种药物.半机械的PK/PD模型

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