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万古霉素药代动力学参数在儿科重症监护病房治疗儿童中的临床应用价值

Clinical Application Value of Pharmacokinetic Parameters of Vancomycin in Children Treated in the Pediatric Intensive Care Unit.

作者信息

Zhou Bo, Xiong Wenyi, Bai Ke, Dang Hongxing, Li Jing, Xu Feng, Fu Yue-Qiang, Liu Chengjun

机构信息

Department of Pharmacy, Children's Hospital of Chongqing Medical University, Chongqing, China.

National Clinical Research Center for Child Health and Disorders, Chongqing, China.

出版信息

Front Pediatr. 2022 Jun 30;10:867712. doi: 10.3389/fped.2022.867712. eCollection 2022.

Abstract

OBJECTIVE

To explore the efficacy and safety of vancomycin as measured by pharmacokinetic/pharmacodynamic parameters in children with severe infection in the Pediatric Intensive Care Unit (PICU) and to determine the appropriate threshold for avoiding nephrotoxicity.

METHODS

The medical records of hospitalized children with severe infection treated with vancomycin in the PICU of a tertiary pediatric hospital from September 2018 to January 2021 were retrospectively collected. Univariate analysis was used to assess the correlation between vancomycin pharmacokinetic/pharmacodynamic parameters and therapeutic efficacy or vancomycin-related nephrotoxicity. Binary logistic regression was used to analyze the risk factors for vancomycin-related nephrotoxicity. The vancomycin area under the concentration-time curve over 24 h (AUC) threshold was determined by receiver operating characteristic (ROC) curve analysis.

RESULTS

One hundred and 10 patients were included in this study. Seventy-six patients (69.1%) exhibited clinically effective response, while the rest exhibited clinically ineffective response. There were no significant differences in APACHE II score, steady-state trough concentration, peak concentration or AUC of vancomycin between the effective and ineffective groups. Among the 110 patients, vancomycin-related nephrotoxicity occurred in 15 patients (13.6%). Multivariate analysis showed that vancomycin treatment duration, trough concentration, and AUC were risk factors for vancomycin-related nephrotoxicity. The ROC curve indicated that AUC < 537.18 mg.h/L was a suitable cutoff point for predicting vancomycin-related nephrotoxicity.

CONCLUSION

No significant correlations were found between the trough concentration or AUC of vancomycin and therapeutic efficacy when the daily dose of vancomycin was approximately 40 mg/kg d, while the trough concentration and AUC were both closely related to vancomycin-related nephrotoxicity. The combination of AUC and trough concentration for therapeutic drug monitoring may reduce the risk of nephrotoxicity.

摘要

目的

通过药代动力学/药效学参数探讨万古霉素在儿科重症监护病房(PICU)重症感染患儿中的疗效和安全性,并确定避免肾毒性的合适阈值。

方法

回顾性收集2018年9月至2021年1月在一家三级儿科医院PICU接受万古霉素治疗的重症感染住院患儿的病历。采用单因素分析评估万古霉素药代动力学/药效学参数与治疗效果或万古霉素相关肾毒性之间的相关性。采用二元逻辑回归分析万古霉素相关肾毒性的危险因素。通过受试者工作特征(ROC)曲线分析确定万古霉素24小时浓度-时间曲线下面积(AUC)阈值。

结果

本研究共纳入110例患者。76例患者(69.1%)表现出临床有效反应,其余患者表现出临床无效反应。有效组和无效组之间的APACHE II评分、万古霉素稳态谷浓度、峰浓度或AUC无显著差异。110例患者中,15例(13.6%)发生万古霉素相关肾毒性。多因素分析显示,万古霉素治疗持续时间、谷浓度和AUC是万古霉素相关肾毒性的危险因素。ROC曲线表明,AUC < 537.18 mg·h/L是预测万古霉素相关肾毒性的合适截断点。

结论

当万古霉素日剂量约为40 mg/kg d时,万古霉素的谷浓度或AUC与治疗效果之间未发现显著相关性,而谷浓度和AUC均与万古霉素相关肾毒性密切相关。联合AUC和谷浓度进行治疗药物监测可能会降低肾毒性风险。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8500/9279905/acddcb167f11/fped-10-867712-g001.jpg

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