Comprehensive Guidance for Antibiotic Dosing in Obese Adults
Comprehensive Guidance for Antibiotic Dosing in Obese Adults
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DOI：
10.1002/phar.2023
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发表时间：
2017-11-01
期刊：
影响因子：
4.1
通讯作者：
Deresinski, Stan C.
中科院分区：
文献类型：
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作者：
Meng, Lina;Mui, Emily;Deresinski, Stan C.
在肥胖中观察到的生理变化通常会影响抗生素的药代动力学（PK）和药效学（PD），并可能导致在这个不断扩大但研究不足的人群中给药不佳。迄今为止，大部分已发表的临床和PK证据包括小患者人群，并且是回顾性的，结果不常见，在某些情况下是矛盾的。在过去的10年中，出现了额外的抗菌药物PK/PD和临床数据，包括延长输注策略和重症人群的检查，以告知肥胖症的抗菌药物剂量。在这篇叙述性综述中，我们对肥胖成人的给药、PK和可能的给药策略进行了批判性综述。我们使用医学主题词检索PubMed、Scopus和科克伦图书馆，包括抗感染药、特定抗菌药物名称、肥胖、药代动力学等。我们回顾了文章，交叉引用了选定的引用文献，并在适用时引用了药物数据库和包装说明书，以制定剂量建议。我们对关于PK和给药问题的现有数据进行了全面的严格审查，包括严重肥胖的危重病和非危重病患者的给药建议。我们根据检索策略确定的2336篇文章中的121篇，为34种抗菌药物制定了剂量建议。尽管其中11种似乎不需要调整剂量，但仍为其余23种抗菌药物提供了针对肥胖症的剂量指南。需要更多的研究来更好地理解和解决关于抗生素PK的不一致的已发表结果，以建立肥胖成人的最佳给药策略。对于时间依赖性抗生素，应考虑替代给药策略，如延长输注时间（例如，- 内酰胺类），以可靠地实现PD目标。在这一人群和其他人群中，跨抗菌药物谱的治疗药物监测越来越重要，以确保优化给药。
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., -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.