Table1_Relationship Between Mean Vancomycin Trough Concentration and Mortality in Critically Ill Patients: A Multicenter Retrospective Study.DOCX

Background: It remains unclear whether the mean vancomycin trough concentration (VTC) derived from the entire course of therapy is of potential benefit for critically ill patients. This study was conducted to explore the association between mean serum VTC and mortality in intensive care units (ICUs).
Methods: 3,603 adult patients with two or more VTC records after receiving vancomycin treatment in the eICU Collaborative Research Database were included in this multicenter retrospective cohort study. Mean VTC was estimated using all measured VTCs and investigated as a continuous and categorical variable. Patients were categorised into four groups according to mean VTC: <10, 10–15, 15–20, and >20 mg/L. Multivariable logistic regression and subgroup analyses were performed to investigate the relationship of mean VTC with mortality.
Results: After adjusting for a series of covariates, logistic regression analyses indicated that mean VTC, as a continuous variable, was positively correlated with ICU (odds ratio, 1.038, 95% confidence interval, [1.014–1.063]) and hospital (1.025 [1.005–1.046]) mortalities. As a categorical variable, mean VTC of 10–15 mg/L was not associated with reduced ICU (1.705 [0.975–2.981]) and hospital (1.235 [0.829–1.841]) mortalities. Mean VTC of 15–20 mg/L was not correlated with a lower risk of hospital mortality (1.370 [0.924–2.029]). Moreover, mean VTCs of 15–20 and >20 mg/L were significantly associated with higher ICU mortality (1.924 [1.111–3.332]; 2.428 [1.385–4.258]), and mean VTC of >20 mg/L with higher hospital mortality (1.585 [1.053–2.387]) than mean VTC of <10 mg/L. Similar results were observed in patients with different Acute Physiology and Chronic Health Evaluation IV score, creatinine clearance, age, and body mass index subgroups.
Conclusion: Mean VTC was not associated with reduced ICU/hospital related mortality. Our results suggested that VTC monitoring might not guarantee vancomycin efficacy for ICU patients.

背景：目前尚不清楚基于整个治疗疗程计算的平均万古霉素谷浓度（vancomycin trough concentration, VTC）是否对重症患者存在潜在获益。本研究旨在探讨重症监护病房（intensive care units, ICUs）内平均血清VTC与患者死亡率之间的关联。
方法：本多中心回顾性队列研究纳入了eICU协作研究数据库（eICU Collaborative Research Database）中，接受万古霉素治疗后拥有2条及以上VTC记录的3603名成年患者。研究采用所有实测VTC值估算平均VTC，并将其分别作为连续变量与分类变量进行分析。根据平均VTC水平将患者分为四组：<10 mg/L、10~15 mg/L、15~20 mg/L以及>20 mg/L。本研究采用多变量logistic回归分析与亚组分析，探究平均VTC与患者死亡率的关联。
结果：校正一系列混杂因素后，logistic回归分析结果显示，作为连续变量的平均VTC与重症监护病房死亡率（比值比：1.038，95%置信区间：[1.014–1.063]）及住院死亡率（1.025，[1.005–1.046]）呈正相关。作为分类变量时，平均VTC为10~15 mg/L的患者，其重症监护病房死亡率（1.705，[0.975–2.981]）与住院死亡率（1.235，[0.829–1.841]）并未出现显著降低。平均VTC为15~20 mg/L的患者，其住院死亡风险并未出现显著降低（1.370，[0.924–2.029]）。此外，相较于平均VTC<10 mg/L的患者，平均VTC为15~20 mg/L与>20 mg/L的患者重症监护病房死亡率显著升高（分别为1.924，[1.111–3.332]；2.428，[1.385–4.258]），且平均VTC>20 mg/L的患者住院死亡率亦显著升高（1.585，[1.053–2.387]）。在不同急性生理学与慢性健康状况评分IV（Acute Physiology and Chronic Health Evaluation IV, APACHE IV）亚组、肌酐清除率（creatinine clearance）亚组、年龄亚组及体重指数（body mass index, BMI）亚组的患者中，均观察到了相似的结果。
结论：平均VTC与重症监护病房/住院死亡率的降低并无关联。本研究结果提示，对VTC进行监测或许无法确保重症监护病房患者的万古霉素治疗疗效。