Hartman Stan J F, Brüggemann Roger J, Orriëns Lynn, Dia Nada, Schreuder Michiel F, de Wildt Saskia N
Department of Pharmacology-Toxicology, Radboudumc, Geert Grooteplein Zuid 10, 6525 GA, Nijmegen, The Netherlands.
Department of Pharmacy, Radboudumc, Nijmegen, The Netherlands.
Clin Pharmacokinet. 2020 Feb;59(2):173-205. doi: 10.1007/s40262-019-00813-w.
Pharmacokinetics (PK) are severely altered in critically ill patients due to changes in volume of distribution (Vd) and/or drug clearance (Cl). This affects the target attainment of antibiotics in critically ill children. We aimed to identify gaps in current knowledge and to compare published PK parameters and target attainment of antibiotics in critically ill children to healthy children and critically ill adults.
Systematic literature search in PubMed, EMBASE and Web of Science. Articles were labelled as relevant when they included information on PK of antibiotics in critically ill, non-neonatal, pediatric patients. Extracted PK-parameters included Vd, Cl, (trough) concentrations, AUC, probability of target attainment, and elimination half-life.
50 relevant articles were identified. Studies focusing on vancomycin were most prevalent (17/50). Other studies included data on penicillins, cephalosporins, carbapenems and aminoglycosides, but data on ceftriaxone, ceftazidime, penicillin and metronidazole could not be found. Critically ill children generally show a higher Cl and larger Vd than healthy children and critically ill adults. Reduced target-attainment was described in critically ill children for multiple antibiotics, including amoxicillin, piperacillin, cefotaxime, vancomycin, gentamicin, teicoplanin, amikacin and daptomycin. 38/50 articles included information on both Vd and Cl, but a dosing advice was given in only 22 articles.
The majority of studies focus on agents where TDM is applied, while other antibiotics lack data altogether. The larger Vd and higher Cl in critically ill children might warrant a higher dose or extended infusions of antibiotics in this patient population to increase target-attainment. Studies frequently fail to provide a dosing advice for this patient population, even if the necessary information is available. Our study shows gaps in current knowledge and encourages future researchers to provide dosing advice for special populations whenever possible.
由于分布容积（Vd）和/或药物清除率（Cl）的变化，危重症患者的药代动力学（PK）会发生严重改变。这影响了危重症儿童抗生素的目标达成情况。我们旨在找出当前知识中的差距，并比较已发表的危重症儿童与健康儿童及危重症成人的抗生素PK参数和目标达成情况。
在PubMed、EMBASE和科学网进行系统的文献检索。当文章包含危重症非新生儿儿科患者抗生素PK的信息时，将其标记为相关文章。提取的PK参数包括Vd、Cl、（谷）浓度、AUC、目标达成概率和消除半衰期。
共识别出50篇相关文章。关注万古霉素的研究最为普遍（17/50）。其他研究包括青霉素类、头孢菌素类、碳青霉烯类和氨基糖苷类的数据，但未找到头孢曲松、头孢他啶、青霉素和甲硝唑的数据。危重症儿童的Cl通常高于健康儿童和危重症成人，Vd也更大。多项抗生素在危重症儿童中的目标达成率降低，包括阿莫西林、哌拉西林、头孢噻肟、万古霉素、庆大霉素、替考拉宁、阿米卡星和达托霉素。50篇文章中有38篇包含Vd和Cl的信息，但只有22篇给出了给药建议。
大多数研究集中在应用治疗药物监测（TDM）的药物上，而其他抗生素则完全缺乏数据。危重症儿童更大的Vd和更高的Cl可能需要在该患者群体中提高抗生素剂量或延长输注时间以提高目标达成率。即使有必要的信息，研究也常常未能为该患者群体提供给药建议。我们的研究揭示了当前知识中的差距，并鼓励未来的研究人员尽可能为特殊人群提供给药建议。
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