Department of Pharmacy, Stanford Health Care, Stanford, California.
Stanford Antimicrobial Safety and Sustainability Program, Stanford Health Care, Stanford, California.
Pharmacotherapy. 2017 Nov;37(11):1415-1431. doi: 10.1002/phar.2023. Epub 2017 Oct 30.
Physiologic alterations seen in obesity commonly impact the pharmacokinetics (PK) and pharmacodynamics (PD) of antibiotics and may result in suboptimal dosing in this expanding but understudied population. Much of the published clinical and PK evidence to date consists of small patient populations and are retrospective with, not infrequently, heterogeneous results that in some cases are contradictory. In the last 10 years, additional antimicrobial PK/PD and clinical data encompassing prolonged infusion strategies and examination of critically ill populations have emerged to inform antimicrobial dosing in obesity. In this narrative review, we critically review literature on dosing, PK, and possible dosing strategies in obese adults. We searched PubMed, Scopus, and the Cochrane Library using Medical Subject Headings including anti-infectives, specific antimicrobial names, obese, pharmacokinetics, and others. We reviewed articles, cross-referenced select cited references, and when applicable, referenced drug databases and package inserts to develop dosing recommendations. We provide an overall critical review of the available data regarding PK and dosing issues including dosing recommendations in both critically ill and noncritically ill patients with significant obesity. We developed dosing recommendations for 34 antimicrobials based on 121 articles of the 2336 identified by the search strategy. Although 11 of these do not appear to require dose adjustment, obesity-specific dosing guidance is provided for the remaining 23 antimicrobials. Additional studies are needed to better understand and resolve discrepant published results regarding the PK of antibiotics to establish optimal dosing strategies in obese adults. Alternative dosing strategies, such as extended infusions, should be considered for time-dependent antibiotics (e.g., β-lactams) in obese patients to achieve PD targets reliably. Therapeutic drug monitoring across the spectrum of antimicrobials is of increasing importance in this and other populations to ensure optimized dosing.
肥胖症患者常出现生理变化，这些变化会影响抗生素的药代动力学（PK）和药效动力学（PD），并可能导致在这一不断扩大但研究不足的人群中剂量不足。迄今为止，大部分已发表的临床和 PK 证据来自于小患者人群，且多数为回顾性研究，结果往往不一致，有些情况下甚至相互矛盾。在过去的 10 年中，出现了更多涵盖延长输注策略的抗菌 PK/PD 和临床数据，并对重症患者人群进行了检查，为肥胖患者的抗菌药物剂量提供了信息。在本综述中，我们批判性地回顾了关于肥胖成人剂量、PK 和可能的剂量策略的文献。我们使用包括抗感染药物、特定抗菌药物名称、肥胖、药代动力学等在内的医学主题词，在 PubMed、Scopus 和 Cochrane 图书馆中进行了搜索。我们对文章进行了综述，交叉引用了选定的参考文献，并在适用的情况下，参考了药物数据库和药物说明书，以制定剂量建议。我们对有关 PK 和剂量问题的现有数据进行了全面的批判性评估，包括对患有严重肥胖症的重症和非重症患者的剂量建议。我们根据 121 篇文章中的数据为 34 种抗菌药物制定了剂量建议，其中 2336 篇文章是通过搜索策略确定的。尽管其中 11 种药物似乎不需要调整剂量，但我们为其余 23 种抗菌药物提供了肥胖症特异性剂量指南。需要进一步研究以更好地了解和解决有关抗生素 PK 的不一致的已发表结果，以确定肥胖成人的最佳剂量策略。对于肥胖患者，应考虑使用延长输注等替代剂量策略来可靠地实现 PD 目标，尤其是对时间依赖性抗生素（如β-内酰胺类）。在这个人群和其他人群中，越来越需要进行治疗药物监测，以确保优化剂量。
