Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California at San Diego, La Jolla, CA, USA.
Department of Pediatrics, Division of Infectious Diseases, University of California at San Diego, La Jolla, CA, USA.
J Clin Pharmacol. 2018 Oct;58 Suppl 10:S108-S122. doi: 10.1002/jcph.1128.
The selection of the right antibiotic and right dose necessitates clinicians understand the contribution of pharmacokinetic variability stemming from age-related physiologic maturation and the pharmacodynamics to optimize drug exposure for clinical response. The complexity of selecting the right dose arises from the multiplicity of pediatric age groups, from premature neonates to adolescents. Body size and age (which relate to organ function) must be incorporated to optimize antibiotic dosing in this vulnerable population. In the effort to optimize and individualize drug dosing regimens, clinical pharmacometrics that incorporate population-based pharmacokinetic modeling, Bayesian estimation, and Monte Carlo simulations are utilized as a quantitative approach to understanding and predicting the pharmacology and clinical and microbiologic efficacy of antibiotics. In addition, opportunistic study designs and alternative blood sampling strategies can serve as practical approaches to ensure successful conduct of pediatric studies. This review article examines relevant literature on optimization of antibiotic pharmacotherapy in pediatric populations published within the last decade. Specific pediatric antibiotic data, including beta-lactam antibiotics, aminoglycosides, and vancomycin, are critically evaluated.
选择合适的抗生素和剂量需要临床医生了解源于年龄相关生理成熟和药效学的药代动力学变异性的贡献，以优化药物暴露以获得临床反应。选择正确剂量的复杂性源于儿科年龄组的多样性，从早产儿到青少年。必须结合体型和年龄（与器官功能有关）来优化这个脆弱人群的抗生素剂量。为了优化和个体化药物剂量方案，临床药代动力学结合基于人群的药代动力学建模、贝叶斯估计和蒙特卡罗模拟被用作一种定量方法来理解和预测抗生素的药理学、临床和微生物疗效。此外，机会性研究设计和替代采血策略可以作为确保儿科研究成功进行的实用方法。本文综述了过去十年中发表的关于儿科人群抗生素治疗优化的相关文献。对特定的儿科抗生素数据，包括β-内酰胺类抗生素、氨基糖苷类和万古霉素进行了批判性评估。
