模型指导下的精准给药对囊性纤维化患儿万古霉素暴露目标达成的影响。

Impact of model-informed precision dosing on achievement of vancomycin exposure targets in pediatric patients with cystic fibrosis.

机构信息

Department of Pediatrics, Stanford University, Palo Alto, California, USA.

Department of Pharmacy, Lucile Packard Children's Hospital Stanford, Palo Alto, California, USA.

出版信息

Pharmacotherapy. 2023 Oct;43(10):1007-1014. doi: 10.1002/phar.2845. Epub 2023 Jul 11.

DOI:10.1002/phar.2845

PMID:37401162

Abstract

BACKGROUND

Vancomycin is commonly used to treat acute pulmonary exacerbations in pediatric patients with cystic fibrosis (CF) and a history of methicillin-resistant Staphylococcus aureus. Optimizing vancomycin exposure during therapy is essential and area under-the-curve (AUC)-guided dosing is now recommended. Model-informed precision dosing (MIPD) utilizing Bayesian forecasting is a powerful approach that can support AUC-guided dose individualization. The objective of the current study was to examine the impact of implementing an AUC-guided dose individualization approach supported via a MIPD clinical decision support (CDS) tool on vancomycin exposure, target attainment rate, and safety in pediatric patients with CF treated with vancomycin during clinical care.

METHODS

A retrospective chart review was performed in patients with CF at a single children's hospital comparing pre- and post-implementation of a MIPD approach for vancomycin supported by a cloud-based, CDS tool integrated into the electronic health record (EHR). In the pre-MIPD period, vancomycin starting doses of 60 mg/kg/day (<13 years) or 45 mg/kg/day (≥13 years) were used. Dose adjustment was guided by therapeutic drug monitoring (TDM) with a target trough 10-20 mg/L. In the post-MIPD period, starting dose and dose adjustment were based on the MIPD CDS tool predictions with a target 24 h AUC (AUC ) 400-600 mg*h/L. Exposure and target achievement rates were retrospectively calculated and compared. Rates of acute kidney injury (AKI) were also compared.

RESULTS

Overall, 23 patient courses were included in the pre-MIPD period and 21 patient courses in the post-MIPD period. In the post-MIPD period, an individualized MIPD starting dose resulted in 71% of patients achieving target AUC compared to 39% in the pre-MIPD period (p < 0.05). After the first TDM and dose adjustment, target AUC achievement was also higher post-MIPD versus pre-MIPD (86% vs. 57%; p < 0.05). AKI rates were low and similar between periods (pre-MIPD 8.7% vs. post-MIPD 9.5%; p = 0.9).

CONCLUSION

An MIPD approach implemented within a cloud-based, EHR-integrated CDS tool safely supported vancomycin AUC-guided dosing and resulted in high rates of target achievement.

摘要

背景

万古霉素常用于治疗有耐甲氧西林金黄色葡萄球菌病史的囊性纤维化（CF）儿科患者的急性肺部恶化。优化治疗期间的万古霉素暴露量至关重要，目前推荐使用曲线下面积（AUC）指导剂量。利用贝叶斯预测的模型指导精准剂量（MIPD）是一种强大的方法，可以支持 AUC 指导的剂量个体化。本研究的目的是评估在临床护理中使用万古霉素治疗 CF 患者时，通过基于云的、集成到电子病历（EHR）中的临床决策支持（CDS）工具实施 AUC 指导剂量个体化方法对万古霉素暴露量、目标达标率和安全性的影响。

方法

对单家儿童医院的 CF 患者进行回顾性图表审查，比较在使用基于云的、集成到 EHR 中的 CDS 工具支持的 MIPD 方法之前和之后，万古霉素的暴露量、目标达标率和安全性。在 MIPD 前，使用 60mg/kg/天（<13 岁）或 45mg/kg/天（≥13 岁）的万古霉素起始剂量。根据治疗药物监测（TDM），以 10-20mg/L 的目标谷浓度调整剂量。在 MIPD 后，起始剂量和剂量调整基于 MIPD CDS 工具预测，目标 24 小时 AUC（AUC）为 400-600mg*h/L。回顾性计算并比较暴露量和目标达标率。还比较了急性肾损伤（AKI）的发生率。

结果

总体而言，MIPD 前有 23 个患者疗程，MIPD 后有 21 个患者疗程。在 MIPD 后，个体化 MIPD 起始剂量使 71%的患者达到目标 AUC，而 MIPD 前为 39%（p<0.05）。在第一次 TDM 和剂量调整后，MIPD 后目标 AUC 的达成率也高于 MIPD 前（86%比 57%；p<0.05）。AKI 发生率较低，且在两个时期相似（MIPD 前 8.7%，MIPD 后 9.5%；p=0.9）。