通过间歇性,长时间或连续输注给的β-乳剂的标准和高剂量的定义:PK/PD模拟研究
Sylvain Goutelle1,2,3, Vincent Jullien4,5, Jean-Pierre Bru6
1Hospices Civils de Lyon, Groupement Hospitalier Nord, Service de Pharmacie, Lyon, France.
欧洲抗生素敏感性测试委员会 (EUCAST) 的新指南要求使用标准剂量和高剂量的抗生素. 这项研究评估了可注射β-乳糖胺的长时间输液 (PI) 和持续输液 (CI) 剂量,确定了最佳抗菌素敏感性的替代方案.
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
- 临床微生物学 临床微生物学
背景情况:
- 欧洲抗生素敏感性测试委员会 (EUCAST) 在2020年更新了抗生素敏感性类别,需要标准和高剂量的抗生素.
- 目前关于注射β-乳酸的建议主要仅为短时间输液方案定义这些剂量.
研究的目的:
- 评估和定义通过长时间输注 (PI) 和连续输注 (CI) 给药的β-乳糖抗生素的标准和高剂量.
- 确定替代剂量方案,以确保适当的药理动力学/药理动力学 (PK/PD) 目标与EUCAST断点保持一致.
主要方法:
- 蒙特卡洛模拟用于七种可注射β-乳酸盐 (阿兹特雷诺,塞菲皮姆,塞福塔克西姆,塞福西丁,塞夫塔齐迪姆,皮佩拉西林,泰莫西林).
- 模拟评估了虚拟患者的各种剂量方案 (短期输注,PI,CI),使用人群PK模型和EUCAST目标/断点.
- 可接受性是基于实现药理动力学/药理动力学 (PK/PD) 目标和与推剂量相比的目标实现概率 (PTA) 值.
主要成果:
- 大多数标准的EUCAST短时间输液方案都显示出足够的PTA.
- 使用PI (34小时) 或CI的9种标准和14种高剂量疗法被确定为可接受的替代方案.
- 对于Pseudomonas spp. 的情况. 感染,PI或CI疗法对于塞费皮姆和阿兹特雷诺南来说至关重要,以达到足够的PTA,并提供了具体的例子.
结论:
- 预计已确定的PI和CI的替代标准和高剂量疗法将与新的EUCAST敏感性定义和MIC断点保持一致.
- 这些发现为优化β-乳酸治疗提供了关键数据,符合不断变化的抗菌素敏感性指南.
- 建议进行进一步的临床验证,以确认这些替代剂量策略的有效性和安全性.
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