Minotti Chiara, Barbieri Elisa, Doni Denis, Impieri Cristina, Giaquinto Carlo, Donà Daniele
Division of Pediatric Infectious Diseases, Department of Women's and Children's Health, University of Padova, Padova, Italy.
Department of Women's and Children's Health, University of Padova, Padova, Italy.
Front Pediatr. 2022 Apr 26;10:868513. doi: 10.3389/fped.2022.868513. eCollection 2022.
Dosing recommendations for anti-infective medicines in children with pre-existing kidney dysfunction are derived from adult pharmacokinetics studies and adjusted to kidney function. Due to neonatal/pediatric age and kidney impairment, modifications in renal clearance and drug metabolism make standard anti-infective dosing for children and neonates inappropriate, with a risk of drug toxicity or significant underdosing. The aim of this study was the systematic description of the use of anti-infective medicines in pediatric patients with pre-existing kidney impairment.
A systematic review of the literature was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The EMBASE, Medline and Cochrane databases were searched on September 21st, 2021. Studies in all languages reporting data on pre-defined outcomes (pharmacokinetics-PK, kidney function, safety and efficacy) regarding the administration of anti-infective drugs in children up to 18 years with pre-existing kidney dysfunction were included.
29 of 1,792 articles were eligible for inclusion. There were 13 case reports, six retrospective studies, nine prospective studies and one randomized controlled trial (RCT), reporting data on 2,168 pediatric patients. The most represented anti-infective class was glycopeptides, with seven studies on vancomycin, followed by carbapenems, with five studies, mostly on meropenem. Antivirals, aminoglycosides and antifungals counted three articles, followed by combined antibiotic therapy, cephalosporins, lipopeptides with two studies, respectively. Penicillins and polymixins counted one study each. Nine studies reported data on patients with a decreased kidney function, while 20 studies included data on kidney replacement therapy (KRT). Twenty-one studies reported data on PK. In 23 studies, clinical outcomes were reported. Clinical cure was achieved in 229/242 patients. There were four cases of underdosing, one case of overdosing and 13 reported deaths.
This is the first systematic review providing evidence of the use of anti-infective medicines in pediatric patients with impaired kidney function or requiring KRT. Dosing size or interval adjustments in pediatric patients with kidney impairment vary according to age, critical illness status, decreased kidney function and dialysis type. Our findings underline the relevance of population PK in clinical practice and the need of developing predictive specific models for critical pediatric patients.
已有肾功能不全的儿童抗感染药物给药建议源自成人药代动力学研究并根据肾功能进行调整。由于新生儿/儿童年龄及肾功能损害，肾脏清除率和药物代谢的改变使得儿童和新生儿的标准抗感染药物给药并不合适，存在药物毒性或剂量严重不足的风险。本研究的目的是系统描述已有肾功能损害的儿科患者使用抗感染药物的情况。
根据系统评价和Meta分析的首选报告项目（PRISMA）指南对文献进行系统评价。于2021年9月21日检索了EMBASE、Medline和Cochrane数据库。纳入所有语言的研究，这些研究报告了关于18岁以下已有肾功能不全儿童使用抗感染药物的预定义结局（药代动力学-PK、肾功能、安全性和疗效）的数据。
1792篇文章中有29篇符合纳入标准。有13篇病例报告、6篇回顾性研究、9篇前瞻性研究和1项随机对照试验（RCT），报告了2168例儿科患者的数据。最具代表性的抗感染药物类别是糖肽类，有7项关于万古霉素的研究，其次是碳青霉烯类，有5项研究，主要是关于美罗培南。抗病毒药物、氨基糖苷类和抗真菌药物各有3篇文章，其次是联合抗生素治疗、头孢菌素类、脂肽类，各有2项研究。青霉素类和多粘菌素类各有1项研究。9项研究报告了肾功能减退患者的数据，20项研究纳入了肾脏替代治疗（KRT）的数据。21项研究报告了PK数据。23项研究报告了临床结局。242例患者中有229例实现了临床治愈。有4例剂量不足、1例剂量过量和13例报告死亡。
这是第一项系统评价，提供了已有肾功能损害或需要KRT的儿科患者使用抗感染药物的证据。已有肾功能损害的儿科患者的给药剂量或间隔调整因年龄、危重病状态、肾功能减退和透析类型而异。我们的研究结果强调了群体PK在临床实践中的相关性以及为危重症儿科患者开发预测性特定模型的必要性。
