万古霉素在囊性纤维化患者中的药代动力学监测：是否是时候超越谷浓度了？
Pharmacokinetic Monitoring of Vancomycin in Cystic Fibrosis: Is It Time to Move Past Trough Concentrations?
机构信息
From the Department of Pharmacy Practice, University at Buffalo School of Pharmacy and Pharmaceutical Sciences, Buffalo, NY.
出版信息
Pediatr Infect Dis J. 2019 Mar;38(3):258-262. doi: 10.1097/INF.0000000000002088.
BACKGROUND
A correlation between vancomycin (VAN) trough concentrations (VTC) and area under the curve (AUC) to minimum inhibitory concentration (MIC) ratio (AUC/MIC) has not been established in children/adolescents with cystic fibrosis (CF). The primary objective of this study was to determine the correlation between measured VTCs and AUC/MIC using population-based pharmacokinetics.
METHODS
A retrospective cohort study of children/adolescents diagnosed with CF, 6 to <18 years of age, treated with VAN for methicillin-resistant Staphylococcus aureus infection was conducted. The relationship between final VTCs and calculated AUC/MIC was assessed using Pearson and Spearman correlations. All tests were 2-tailed with alpha set at 0.05.
RESULTS
Thirty children/adolescents, 7 to 17 years of age (median age 15 year; interquartile range: 9-17 years), were included. The mean final VAN dose was 58.03 ± 18.58 mg/kg/d, and the median final VTC was 12.6 (11-13.6) mg/L. The mean AUC/MIC was 355.34 ± 138.46 (Le model) versus 426.79 ± 178.92 (Stockmann model; P = 0.089). No correlation existed between VTCs and AUC/MIC using either the model by Le (r = 0.140; P = 0.461) or Stockmann (r = 0.115; P = 0.564). Using the Stockmann model, VAN dose (mg/kg/dose) was found to have a strong positive correlation with AUC (r = 0.8874; P < 0.0001) and AUC/MIC (r = 0.7877; P < 0.0001).
CONCLUSIONS
VTCs did not correlate with AUC or AUC/MIC. Further research is needed to determine which estimate of VAN treatment efficacy is most appropriate for children and adolescents with CF infected with methicillin-resistant Staphylococcus aureus.
背景
万古霉素（VAN）谷浓度（VTC）与最低抑菌浓度（MIC）比值的 AUC（AUC/MIC）之间的相关性尚未在囊性纤维化（CF）儿童/青少年中建立。本研究的主要目的是使用基于人群的药代动力学来确定测量的 VTC 与 AUC/MIC 之间的相关性。
方法
对 6 至<18 岁诊断为 CF、接受 VAN 治疗耐甲氧西林金黄色葡萄球菌感染的儿童/青少年进行回顾性队列研究。使用 Pearson 和 Spearman 相关性评估最终 VTC 与计算的 AUC/MIC 之间的关系。所有测试均为双侧检验，α 值设为 0.05。
结果
纳入 30 名 7 至 17 岁（中位年龄 15 岁；四分位间距：9-17 岁）的儿童/青少年。平均最终 VAN 剂量为 58.03±18.58mg/kg/d，中位数最终 VTC 为 12.6（11-13.6）mg/L。平均 AUC/MIC 为 355.34±138.46（Le 模型）和 426.79±178.92（Stockmann 模型；P=0.089）。使用 Le 模型（r=0.140；P=0.461）或 Stockmann 模型（r=0.115；P=0.564），VTC 与 AUC/MIC 之间均无相关性。使用 Stockmann 模型，VAN 剂量（mg/kg/dose）与 AUC（r=0.8874；P<0.0001）和 AUC/MIC（r=0.7877；P<0.0001）呈强正相关。
结论
VTC 与 AUC 或 AUC/MIC 不相关。需要进一步研究以确定哪种万古霉素治疗效果的估计值最适合感染耐甲氧西林金黄色葡萄球菌的 CF 儿童/青少年。
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