万古霉素谷浓度、AUC及AUC/MIC比值与肠球菌血症患者临床结局的相关性：一项前瞻性队列研究

Association of vancomycin trough levels, AUC and AUC/MIC ratios with clinical outcomes in patients with enterococcal bacteremia: a prospective cohort study.

作者信息

Sel Eda Kubra, Tufan Berfu, Atagun Gundag Kupra, Oguz Vildan Avkan, Ozbek Ozgen Alpay, Gumustekin Mukaddes, Ucku Serife Reyhan, Gelal Ayse

机构信息

Department of Medical Pharmacology, Dokuz Eylül University Faculty of Medicine, Balçova, İzmir, Türkiye.

Department of Medical Microbiology, Dokuz Eylül University Faculty of Medicine, Balçova, İzmir, Türkiye.

出版信息

BMC Infect Dis. 2025 Jul 29;25(1):958. doi: 10.1186/s12879-025-11400-9.

DOI:10.1186/s12879-025-11400-9

PMID:40731327

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12309136/

Abstract

BACKGROUND

The optimal vancomycin pharmacokinetic/pharmacodynamic (PK/PD) targets for successful treatment of enterococcal infections remain controversial. To clarify these targets, this study investigated the association of the vancomycin area under the curve (AUC), the AUC/minimum inhibitory concentration (MIC) ratio, and the serum trough concentration (C) with clinical outcomes (treatment efficacy, safety, and 30-day mortality) in adult patients with enterococcal bacteremia.

METHODS

This prospective cohort study was conducted at a tertiary university hospital between January 2023–2025 and included adult patients with enterococcal bacteremia who were treated with vancomycin and met predefined inclusion/exclusion criteria. Data were prospectively collected. The associations of the steady-state 24-hour vancomycin AUC (AUC), the AUC/MIC ratio, and the trough concentration (C) with treatment efficacy, safety, and 30-day mortality were evaluated. Bayesian modeling was used to estimate the AUC. Optimal vancomycin PK/PD cutoff values were determined using receiver operating characteristic (ROC) curve analysis.

RESULTS

Among the 53 patients included in the study, treatment was effective in 62.3%, while acute kidney injury (AKI) developed in 47.2%. The 30-day all-cause mortality rate was 28.3%. Regarding treatment efficacy, only the AUC cutoff value was found to be statistically significant; patients with AUC<616 µg·h/mL had a higher rate of efficacy compared to those with AUC≥616 µg·h/mL ( = 0.031). A similar pattern was observed for mortality at this cutoff value ( = 0.041). The highest efficacy was observed in the 400–616 µg·h/mL range (18 out of 22 patients, 82%). The cutoff values for AKI were determined to be 538 µg·h/mL for AUC and 15.7 µg/mL for C. Acute kidney injury occurred in 68.8% of patients with AUC≥538 µg·h/mL and in 14.3% of those with AUC<538 µg·h/mL ( < 0.001). Similarly, the risk of AKI was significantly greater in patients with C≥15.7 µg/mL than in those with C<15.7 µg/mL ( < 0.001).

CONCLUSIONS

In patients with enterococcal bacteremia treated with vancomycin, adjusting the dose to achieve an AUC between 400 and 616 µg·h/mL may be appropriate to ensure effective therapy. However, due to the risk of AKI at these doses, patients should be closely monitored. For safe treatment in cases where AUC monitoring is not feasible, maintaining a serum C below 15.7 µg/mL may be appropriate.

SUPPLEMENTARY INFORMATION

The online version contains supplementary material available at 10.1186/s12879-025-11400-9.

摘要

背景

万古霉素药代动力学/药效学（PK/PD）的最佳靶点对于成功治疗肠球菌感染仍存在争议。为了阐明这些靶点，本研究调查了成人肠球菌血症患者中万古霉素曲线下面积（AUC）、AUC/最低抑菌浓度（MIC）比值以及血清谷浓度（C）与临床结局（治疗效果、安全性和30天死亡率）之间的关联。

方法

本前瞻性队列研究于2023年1月至2025年在一家三级大学医院进行，纳入了接受万古霉素治疗且符合预先定义的纳入/排除标准的成人肠球菌血症患者。数据进行前瞻性收集。评估稳态24小时万古霉素AUC（AUC）、AUC/MIC比值和谷浓度（C）与治疗效果、安全性和30天死亡率之间的关联。采用贝叶斯模型估计AUC。使用受试者工作特征（ROC）曲线分析确定万古霉素PK/PD的最佳截断值。

结果

在纳入研究的53例患者中，62.3%的患者治疗有效，而47.2%的患者发生了急性肾损伤（AKI）。30天全因死亡率为28.3%。关于治疗效果，仅发现AUC截断值具有统计学意义；AUC<616 μg·h/mL的患者与AUC≥616 μg·h/mL的患者相比，有效率更高（P = 0.031）。在该截断值下，死亡率也观察到类似模式（P = 0.041）。在400–616 μg·h/mL范围内观察到最高疗效（22例患者中的18例，82%）。确定AKI的AUC截断值为538 μg·h/mL，C截断值为15.7 μg/mL。AUC≥538 μg·h/mL的患者中68.8%发生了急性肾损伤，而AUC<538 μg·h/mL的患者中14.3%发生了急性肾损伤（P<0.001）。同样，C≥15.7 μg/mL的患者发生AKI的风险显著高于C<15.7 μg/mL的患者（P<0.001）。