在慢性疾病的多药疗法中,最佳的切换策略是慢性疾病的最佳切换策略
Juan Magalang1,2, Javier Aguilar3, Jose Perico Esguerra4
1University of Bern, Bern University Hospital, Department of Visceral Surgery and Medicine, Inselspital, Murtenstrasse 35, Bern 3008, Switzerland.
Physical review. E
|October 21, 2025
概括
抗微生物耐药性威胁到公共卫生. 这项研究引入了一种新型模型,以优化药物治疗,寻找具有成本效益的策略来延迟耐药性发展并改善患者的治疗结果.
科学领域:
- 数学建模的数学建模
- 计算生物学是一种计算生物学.
- 公共卫生 公共卫生
背景情况:
- 抗菌素耐药性 (AMR) 是全球主要的健康威胁,每年造成数百万人的死亡.
- 由于病原体突变的不可预测性,当前的组合疗法和疗法切换等策略面临挑战.
研究的目的:
- 为优化抗菌药物治疗策略开发一个双尺度随机模型.
- 分析药物切换频率和组合治疗对延迟AMR的影响.
- 为了确定具有成本效益的药物交换协议.
主要方法:
- 一个双尺度的随机模型模拟治疗进化在一个多维的疗效空间.
- 纳入治疗开关的随机重置和宿主恢复或抵抗的边界条件.
- 使用兰杰文和主方程,推导平均吸收时间的分析表达式.
- 包括对治疗数量和成本的限制,并扩展到单细胞异质性.
主要成果:
- 通过考虑连续和离散的基因组变化,获得了平均吸收时间的分析表达式.
- 该模型确定了最佳的药物交换协议,以平衡耐药性延迟与治疗成本.
- 药物交换间隔和药物数量的相关性与AMR发展时间表进行了评估.
- 单细胞异质性被纳入模型个体突变效应.
结论:
- 拟议的模型为优化抗微生物药物治疗策略以打击耐药性提供了一个框架.
- 发现了非碎的最佳方案,表明仔细考虑切换时间和药物组合可以减轻AMR.
- 该模型强调了在治疗设计中考虑基因组变化和宿主-病原体动态的重要性.
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