Imburgia Taylor A, Kussin Michelle L
Department of Pharmacy (TAI), WVU Medicine Children's, Morgantown, WV.
Department of Pharmacy (MLK), Riley Hospital for Children at Indiana University Health and Indiana University School of Medicine, Indianapolis, IN.
J Pediatr Pharmacol Ther. 2022;27(3):214-227. doi: 10.5863/1551-6776-27.3.214. Epub 2022 Mar 21.
Intravenous beta-lactam antibiotics are the most prescribed antibiotic class in US hospitalized patients of all ages; therefore, optimizing their dosing is crucial. Bactericidal killing is best predicted by the time in which beta-lactam drug concentrations are maintained above the organism's minimum inhibitory concentration (MIC), rather than achievement of a high peak concentration. As such, administration of beta-lactam antibiotics via extended or continuous infusions over a minimum of 3 hours, rather than standard infusions over approximately 30 minutes, has been associated with improved achievement of pharmacodynamic targets and improved clinical outcomes in adult medical literature. This review summarizes the pediatric medical literature. Applicable studies include pharmacodynamic models, case series, retrospective analyses, and prospective studies on the use of extended infusion and continuous infusion penicillins, cephalosporins, carbapenems, and monobactams in neonates, infants, children, and adolescents. Specialized patient populations with unique pharmacokinetics and high-risk infections (neonates, critically ill, febrile neutropenia, cystic fibrosis) are also reviewed. While more studies are needed to confirm prospective clinical outcomes, the current body of evidence suggests extended and continuous infusions of beta-lactam antibiotics are well tolerated in children and improve achievement of pharmacokineticpharmacodynamic targets with similar or superior clinical outcomes, particularly in infections associated with high MICs.
静脉注射β-内酰胺类抗生素是美国各年龄段住院患者中处方量最多的抗生素类别;因此,优化其给药剂量至关重要。杀菌效果最好通过β-内酰胺类药物浓度维持在微生物最低抑菌浓度(MIC)以上的时间来预测,而不是通过达到高的峰值浓度来预测。因此,在成人医学文献中,通过至少3小时的延长或持续输注而非大约30分钟的标准输注来给药β-内酰胺类抗生素,与更好地实现药效学目标和改善临床结局相关。本综述总结了儿科医学文献。适用的研究包括药效学模型、病例系列、回顾性分析以及关于在新生儿、婴儿、儿童和青少年中使用延长输注和持续输注青霉素、头孢菌素、碳青霉烯类和单环β-内酰胺类抗生素的前瞻性研究。还对具有独特药代动力学和高风险感染的特殊患者群体(新生儿、重症患者、发热性中性粒细胞减少症、囊性纤维化)进行了综述。虽然需要更多研究来证实前瞻性临床结局,但目前的证据表明,β-内酰胺类抗生素的延长和持续输注在儿童中耐受性良好,并能改善药代动力学-药效学目标的实现,临床结局相似或更好,尤其是在与高MIC相关的感染中。