Pediatric pharmacokinetics of the antibiotics in the access and watch groups of the 2019 WHO model list of essential medicines for children: a systematic review

<b>Introduction</b>: Pharmacokinetic-pharmacodynamic (PK-PD) studies of antibiotics in pediatrics are limited. Pediatric dosing regimens for many antimicrobial drugs have been historically derived from adult pharmacokinetic data. Most pediatric formularies and dosing guidelines globally are expert-based and provide no rationale for the recommended doses, leading to heterogeneous guidance. <b>Areas covered</b>: We systematically reviewed the current dosing for 28 antibiotics listed in the Access and Watch groups of the 2019 World Health Organization (WHO) Essential Medicines List for children (EMLc). PubMed and EMBASE were searched for all PK-PD and pharmacological studies in pediatrics up to May 2018. In total, 262 pediatric related articles were deemed eligible. The most studied drugs were those where therapeutic drug monitoring is routine (aminoglycosides, glycopeptides) and study reporting detail was variable, with only 60.0% using the PK-PD results in make dosing recommendations. Based on this evidence, dose recommendations for each antibiotic were made. <b>Expert opinion</b>: We provide an up-to-date review of the limited available evidence on pediatric dosing for the 28 commonly prescribed antibiotics in the 2019 WHO EMLc. We propose synthesized dosing recommendations for those antibiotics administered systemically for the treatment of serious infections. Further PK-PD studies in children, particularly with underlying conditions, are needed.

### 引言
儿童人群抗菌药物的药代动力学-药效动力学（PK-PD）研究相对匮乏。目前临床多数儿童抗菌药物的给药方案均基于成人药代动力学数据推导而来，全球范围内的多数儿科处方集与给药指南均由专家经验制定，未阐明推荐剂量的依据，导致给药指南标准不一。

### 研究范围
本研究系统综述了2019年世界卫生组织（WHO）儿童基本药物目录（EMLc）中准入组（Access）与监测组（Watch）收录的28种抗菌药物的现行给药方案。研究检索了PubMed与EMBASE数据库截至2018年5月的所有儿科PK-PD及药理学相关研究，最终纳入262篇儿科相关文献。研究最多的药物为常规开展治疗药物监测的品种（如氨基糖苷类、糖肽类），且各研究的报告细节参差不齐，仅60.0%的研究采用PK-PD结果制定给药推荐方案。基于上述证据，本研究为每种抗菌药物制定了给药推荐方案。

### 专家意见
本研究针对2019年WHO儿童基本药物目录中28种临床常用抗菌药物的儿科给药现有有限证据进行了最新综述，并针对用于治疗重症感染的全身用抗菌药物提出了综合给药推荐方案。未来仍需开展更多针对儿童人群（尤其是合并基础疾病者）的PK-PD研究。