Independent Researcher, VancoPK, LLC, Temple, TX, USA.
J Clin Pharm Ther. 2021 Oct;46(5):1426-1432. doi: 10.1111/jcpt.13474. Epub 2021 Jun 25.
The revised vancomycin monitoring guidelines recommend targeting an area under the curve (AUC) of 400-600 mg*hr/L for serious methicillin-resistant Staphylococcus aureus (MRSA) infections. An AUC can be measured by checking a peak and trough concentration at steady state; however, this requires obtaining an additional blood sample. The most practical way to perform AUC-guided dosing is by estimating an AUC from a steady-state trough. The purpose of this study was to compare AUCs estimated from trough-only data to AUCs calculated from peak and trough concentrations.
Steady-state peak and trough data were collected from an open-access clinical calculator VancoPK.com. Patients were included who had (1) peaks drawn ≥60 min after the end of infusion, (2) peak and trough levels drawn ≥4 h apart and (3) troughs drawn ≤4 h early or late. The population was randomized and divided into a model group and test group. A population equation for vancomycin volume of distribution (Vd) was derived and compared to other general adult Vd models. Accuracy and precision of estimated AUCs were measured with bias, root mean square error (RMSE) and Lin's concordance correlation.
A total of 2,500 adult patients were included in the model group and 1,843 were included in the test group. The derived Vd equation, Vd (L) = 0.29(age) +0.33(total BW in kg) +11, produced accurate and precise AUC estimates from trough-only data. The mean actual AUC and estimated AUC were 504 and 503, respectively, with a correlation of 0.926. The RMSE between estimated and actual AUCs was 47.7, meaning that over 95% of estimated AUCs were within 100 points of actual AUCs with the study's Vd model. Other Vd models performed well for certain types of patients, depending on their body weight and age.
There is limited evidence from large, robust populations regarding how to estimate Vd for general adult patients. Accuracy and precision of estimated AUCs depend on the applied population Vd model. The Vd model from the present study can be used for AUC-guided dosing with trough-only data which requires less blood work than peak-trough monitoring. AUC calculations are practical with the use of open-access websites.
修订后的万古霉素监测指南建议针对严重耐甲氧西林金黄色葡萄球菌(MRSA)感染,目标为 AUC 为 400-600mg*hr/L。AUC 可以通过检查稳态时的峰浓度和谷浓度来测量;然而,这需要获得额外的血样。进行 AUC 指导剂量的最实际方法是通过稳态谷值估计 AUC。本研究的目的是比较仅通过谷值数据估计的 AUC 与通过峰谷浓度计算的 AUC。
从开放访问的临床计算器 VancoPK.com 中收集稳态时的峰和谷数据。纳入的患者符合以下条件:(1)输注结束后至少 60 分钟采集峰浓度,(2)峰浓度和谷浓度采集间隔至少 4 小时,(3)谷浓度采集提前或推迟不超过 4 小时。该人群随机分为模型组和测试组。推导了万古霉素分布容积(Vd)的群体方程,并与其他成人通用 Vd 模型进行了比较。通过偏差、均方根误差(RMSE)和林氏一致性相关系数来衡量估计 AUC 的准确性和精密度。
共有 2500 名成年患者纳入模型组,1843 名患者纳入测试组。推导的 Vd 方程 Vd(L)=0.29(年龄)+0.33(总体重[kg])+11,可从仅通过谷值数据准确、精确地估计 AUC。实际 AUC 和估计 AUC 的平均值分别为 504 和 503,相关性为 0.926。估计 AUC 与实际 AUC 之间的 RMSE 为 47.7,这意味着研究的 Vd 模型中,超过 95%的估计 AUC 与实际 AUC 的差值在 100 以内。其他 Vd 模型在特定类型的患者中表现良好,具体取决于他们的体重和年龄。
关于如何为一般成年患者估计 Vd,来自大型、稳健人群的证据有限。估计 AUC 的准确性和精密度取决于应用的群体 Vd 模型。本研究的 Vd 模型可用于仅通过谷值数据进行 AUC 指导剂量,这比峰谷监测需要的血液检测更少。通过使用开放访问网站,AUC 计算是可行的。