From the Departments of Neonatology.
Pediatric Infectious Diseases and Immunology.
Pediatr Infect Dis J. 2021 May 1;40(5):434-439. doi: 10.1097/INF.0000000000002993.
Adequate dosage recommendations are imperative for successful treatment of invasive infections. We evaluated the occurrence of sub- and supratherapeutic serum and cerebrospinal fluid (CSF) concentrations of benzylpenicillin (BPEN) in neonates treated for a severe group B streptococci (GBS) sepsis and/or meningitis as well as discrepancies in dosing recommendations provided by pediatric reference sources.
Retrospective analysis of (pre)term infants treated with BPEN undergoing therapeutic drug monitoring (TDM) between May 2015 and May 2019. Outcomes included numbers of sub- and supratherapeutic concentrations, and dose adjustments, clinical evolution, and dosing recommendations from six pediatric reference sources.
A total of 21 TDM samples from 8 neonates were evaluated. Among serum concentrations, 9/21 (43%) were below and 8/21 (38%) above the pre-specified therapeutic target range of 10-20 mg/L. Only 1 patient had BPEN determined in CSF whose concentration was below the lower limit of quantification. TDM identified a need for dose modification in 10/21 (48%) instances. Three of eight patients exhibited complete resolution of clinical, laboratory and radiologic signs of infection. Substantial variation in dosing recommendations (50,000-400,000 IE/kg/d) was present between reference sources.
Our data reveal that under current dosage recommendations, the predefined target serum or CSF concentrations of BPEN are not achieved in all children. In case of clinical failure, serum and/or CSF BPEN concentrations should be determined. Given the wide variation in concentrations and subsequent dose requirements, further exploration of the clinical and pharmacologic characteristics of BPEN in (pre)term neonates is essential to optimize therapeutic efficacy.
为了成功治疗侵袭性感染，适当的剂量推荐是必不可少的。我们评估了接受治疗的严重 B 组链球菌（GBS）败血症和/或脑膜炎新生儿的苯唑西林（BPEN）血清和/或脑脊液（CSF）浓度低于和高于治疗目标范围（10-20mg/L）的发生率，以及儿科参考来源提供的剂量推荐之间的差异。
回顾性分析 2015 年 5 月至 2019 年 5 月期间接受 BPEN 治疗并进行治疗药物监测（TDM）的（早产）婴儿。结果包括亚治疗和超治疗浓度的数量、剂量调整、临床转归以及来自六个儿科参考来源的剂量推荐。
共评估了 8 名新生儿的 21 份 TDM 样本。在血清浓度中，9/21（43%）低于 10-20mg/L 的预先指定治疗目标范围，8/21（38%）高于该范围。只有 1 名患者的 CSF 中 BPEN 被测定，其浓度低于定量下限。TDM 确定需要在 10/21（48%）的情况下进行剂量调整。8 例患者中有 3 例完全消除了感染的临床、实验室和影像学体征。参考来源之间存在剂量推荐（50,000-400,000IE/kg/d）的显著差异。
我们的数据显示，在目前的剂量推荐下，并非所有儿童的 BPEN 预设目标血清或 CSF 浓度都能达到。在临床治疗失败的情况下，应测定血清和/或 CSF 的 BPEN 浓度。鉴于浓度和随后的剂量需求存在广泛差异，进一步探索 BPEN 在（早产）新生儿中的临床和药理学特征对于优化治疗效果至关重要。
