一项在印度一家三级医疗机构中探索危重症患者万古霉素给药方案适宜性的研究。
A study to explore the appropriateness of dosing regimen of vancomycin in critically ill patients in a tertiary care unit of India.
作者信息
Belavagi Devaraj, Bhandari Ritika Kondel, Shafiq Nusrat, Gota Vikram, Patil Anand, Pandey Avaneesh K, Mothsara Chakrant, Gupta Rajesh, Sahni Neeru, Sharma Navneet, Ray Pallab, Kumar Vivek, Sharma Sunil Kumar, Malhotra Samir
机构信息
MD Pharmacology, Dept of Pharmacology, Post Graduate Institute of Medical Education and Research, Chandigarh, 160012, India.
PhD, Demonstrator, Dept of Pharmacology, Post Graduate Institute of Medical Education and Research, Chandigarh, 160012, India.
出版信息
Germs. 2022 Jun 30;12(2):238-252. doi: 10.18683/germs.2022.1326. eCollection 2022 Jun.
INTRODUCTION
Vancomycin is used in proven or suspected MRSA and MRE infections. An AUC/MIC ratio of ≥400 is the current accepted critical PK/PD"efficacy" target of vancomycin activity. The present study was conducted to ascertain the appropriateness of practice of current dosage regimen of vancomycin (1 g BD) based on population pharmacokinetic approach.
METHODS
A single-center prospective study with the ICU setting of a tertiary care center was conducted. A total of 15 adult patients with sepsis treated with vancomycin were included over 15 months from May 2019 to July 2020. Blood samples were obtained at 5, 10, and 30 minutes and thereafter at 2 and 6 hours following the completion of the vancomycin infusion. The data obtained from HPLC estimation was analyzed using a population pharmacokinetic approach with NLME, Phoenix 8.3.2.166. The pharmacokinetic model was based on covariates such as bodyweight and urinary creatinine clearance to predict drug concentrations.
RESULTS
A total of 83 vancomycin blood samples were analyzed. The mean AUC and AUC in patients who improved and died were (AUC=293 (152.97); AUC=535.14 (353.67) and (AUC=137.19 (51.37); AUC=582.12 (1036.09) respectively, the difference between the two outcome groups was not statistically significant (p=0.104). The pharmacokinetic model was best described by a two-compartment linear model. The goodness-of-fit plots showed that the final covariate pharmacokinetic model (having bodyweight and urinary creatinine clearance) adequately described the observed vancomycin concentrations.
CONCLUSIONS
Based on the finding of the study it was concluded that 1 g BD dosing of vancomycin is inappropriate. Including covariates such as urinary creatinine clearance and weight in the pharmacokinetic model helped predict drug concentrations more accurately. However, further studies are required to demonstrate efficacy regarding applying this strategy.
引言
万古霉素用于已证实或疑似的耐甲氧西林金黄色葡萄球菌（MRSA）和耐万古霉素肠球菌（MRE）感染。AUC/MIC比值≥400是目前公认的万古霉素活性的关键药代动力学/药效学（PK/PD）“疗效”目标。本研究旨在基于群体药代动力学方法确定当前万古霉素剂量方案（1g，每日两次）应用的合理性。
方法
在一家三级医疗中心的重症监护病房（ICU）开展了一项单中心前瞻性研究。2019年5月至2020年7月的15个月期间，共纳入15例接受万古霉素治疗的成年脓毒症患者。在万古霉素输注结束后的5分钟、10分钟和30分钟，以及之后的2小时和6小时采集血样。使用群体药代动力学方法（NLME，Phoenix 8.3.2.166）对通过高效液相色谱（HPLC）测定获得的数据进行分析。药代动力学模型基于体重和尿肌酐清除率等协变量来预测药物浓度。
结果
共分析了83份万古霉素血样。病情改善和死亡患者的平均AUC和AUC分别为（AUC = 293（152.97）；AUC = 535.14（353.67））和（AUC = 137.19（51.37）；AUC = 582.12（1036.09）），两组结局之间的差异无统计学意义（p = 0.104）。药代动力学模型以二室线性模型最佳描述。拟合优度图显示，最终的协变量药代动力学模型（包含体重和尿肌酐清除率）能充分描述观察到的万古霉素浓度。
结论
基于该研究结果得出结论，万古霉素1g每日两次的给药剂量不合适。在药代动力学模型中纳入尿肌酐清除率和体重等协变量有助于更准确地预测药物浓度。然而，需要进一步研究来证实应用该策略的疗效。
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