Tangvichitrerk Piyawadee, Changpradub Dhitiwat, Hemapanpairoa Jatapat, Juntanawiwat Piraporn, Santimaleeworagun Wichai
The College of Pharmacotherapy of Thailand, Nonthaburi, 11000, Thailand.
Somdetphraphutthaloetla Hospital, Samutsongkharm, 75000, Thailand.
BMC Infect Dis. 2025 Jan 28;25(1):133. doi: 10.1186/s12879-024-10399-9.
The optimal pharmacokinetic and pharmacodynamic (PK/PD) parameters of vancomycin that can improve outcomes in enterococcal infections remain controversial. To clarify the therapeutic target for this antibiotic, this study aimed to determine vancomycin PK/PD parameters associated with efficacy in the early (during 72 h) or later (after 72 h) phase of treatment and nephrotoxicity in enterococcal bloodstream infection patients.
This multicenter retrospective study reviewed medical records of patients with enterococcal bloodstream infections treated with intravenous vancomycin infusion for at least 72 h between January 2016 and March 2024 at Phramongkutklao Hospital or Nopparatrajathanee Hospital in Bangkok, and Rachaburi Hospital in Rachaburi Province, Thailand. Patients with data available on serum vancomycin concentration were analyzed. The primary outcomes were 30-day mortality and acute kidney injury. The estimates of the mean 24-h area under the curve in the first 72 h (AUC) and in steady state (AUC) were determined by Bayesian theorem.
Overall, 201 vancomycin concentrations were measured within the first 72 h after vancomycin treatment, while 156 were in a steady state (> 72 h). According to Classification and Regression Tree analysis, vancomycin AUC at 420 mg·h/l was the PK/PD target for 30-day mortality. Results reveal that patients with AUC (early phase) and AUC < 420 mg·h/l (later phase) had significantly higher 14-day, 30-day, and in-hospital mortality than AUC ≥ 420 mg·h/l groups. In addition, patients with AUC ≥ 420 mg·h/l in the early phase had significantly reduced microbiological failure (p = 0.004). Patients with AUC ≥ 700 mg·h/l in early and later phases had significantly increased acute kidney injury risk. In addition, patients receiving concomitant nephrotoxic drugs had an AUC cutoff value of 650 mg·h/l. Multivariate Cox regression analysis showed that vancomycin AUC < 420 mg·h/l, unknown source of bacteremia, and acute kidney injury were significantly associated with 30-day mortality.
AUC 420-650 mg·h/l in early and later phases was the target of vancomycin's PK/PD in enterococcal bacteremia patients for efficacy and to prevent acute kidney injury. This study suggests close monitoring of vancomycin levels to ensure efficacy and safety.
万古霉素能改善肠球菌感染预后的最佳药代动力学和药效学（PK/PD）参数仍存在争议。为明确这种抗生素的治疗靶点，本研究旨在确定肠球菌血流感染患者治疗早期（72小时内）或晚期（72小时后）与疗效相关的万古霉素PK/PD参数以及肾毒性。
这项多中心回顾性研究回顾了2016年1月至2024年3月期间在泰国曼谷的磅贡古考医院或诺帕拉贾他尼医院以及叻丕府的叻丕医院接受静脉输注万古霉素治疗至少72小时的肠球菌血流感染患者的病历。对有血清万古霉素浓度数据的患者进行分析。主要结局为30天死亡率和急性肾损伤。前72小时（AUC）和稳态（AUC）的24小时曲线下平均面积通过贝叶斯定理确定。
总体而言，在万古霉素治疗后的前72小时内测量了201次万古霉素浓度，而156次处于稳态（>72小时）。根据分类回归树分析，万古霉素AUC为420mg·h/l是30天死亡率的PK/PD靶点。结果显示，AUC（早期）和AUC<420mg·h/l（晚期）的患者14天、30天和住院死亡率显著高于AUC≥420mg·h/l组。此外，早期AUC≥420mg·h/l的患者微生物学失败显著减少（p = 0.004）。早期和晚期AUC≥700mg·h/l的患者急性肾损伤风险显著增加。此外，接受联合肾毒性药物治疗的患者AUC临界值为650mg·h/l。多因素Cox回归分析显示，万古霉素AUC<420mg·h/l、菌血症来源不明和急性肾损伤与30天死亡率显著相关。
早期和晚期AUC为420 - 650mg·h/l是肠球菌血症患者万古霉素PK/PD的靶点，以达到疗效并预防急性肾损伤。本研究建议密切监测万古霉素水平以确保疗效和安全性。
