Crandon Jared L, MacVane Shawn H, Nicolau David P
Center for Anti-Infective Research and Development, Hartford Hospital, Hartford, Connecticut.
Pharmacotherapy. 2014 Feb;34(2):203-9. doi: 10.1002/phar.1323. Epub 2013 Jun 24.
To evaluate and compare the percent protein binding of vancomycin in hospitalized patients by using a clinical or research laboratory-derived assay methodology, and to evaluate potential patient characteristics accounting for alterations in protein binding.
Prospective noninterventional cohort study.
Single-center tertiary care medical center.
A total of 55 hospitalized adults who were receiving vancomycin for a suspected or documented infection between August and November 2011 and required therapeutic drug monitoring.
Vancomycin protein-binding studies were conducted by using ultracentrifugation of 63 blood samples collected from the 55 patients for therapeutic drug monitoring as part of clinical practice. Total and free drug concentrations were assayed in the research laboratory by using high-performance liquid chromatography (HPLC) and in the clinical laboratory by using fluorescence polarization immunoassay (FPIA). Multivariate linear regression analysis was performed to identify patient variables that were predictive of vancomycin protein binding. The average protein binding was statistically significantly lower and more variable when assayed by FPIA compared with HPLC (mean ± SD 47.3 ± 13.0% vs 54.6 ± 9.5%, p<0.001). Multivariate analyses showed that after controlling for days of vancomycin therapy, patients in the intensive care unit (ICU) had a protein binding value that was 8.4% lower than non-ICU patients (p=0.005).
Using research laboratory-based HPLC methodology, we identified an average vancomycin protein binding of 54.6% with considerably less variability than reported in the literature using clinical-based assay methodologies. Further, we identified patient factors that may likewise have an impact on this value. Future studies of vancomycin protein binding should consider use of a nonclinical assay to minimize methodological-induced variability.
采用临床或研究实验室衍生的检测方法评估和比较住院患者中万古霉素的蛋白结合率，并评估导致蛋白结合改变的潜在患者特征。
前瞻性非干预队列研究。
单中心三级医疗中心。
2011年8月至11月期间因疑似或确诊感染接受万古霉素治疗且需要进行治疗药物监测的55名住院成人。
作为临床实践的一部分，对从55名患者采集的63份血样进行超速离心，以开展万古霉素蛋白结合研究。研究实验室采用高效液相色谱法（HPLC）、临床实验室采用荧光偏振免疫分析法（FPIA）测定总药物浓度和游离药物浓度。进行多变量线性回归分析以确定可预测万古霉素蛋白结合的患者变量。与HPLC法相比，采用FPIA法测定时，平均蛋白结合率在统计学上显著更低且变异性更大（均值±标准差47.3±13.0% 对54.6±9.5%，p<0.001）。多变量分析显示，在控制万古霉素治疗天数后，重症监护病房（ICU）患者的蛋白结合值比非ICU患者低8.4%（p=0.005）。
使用基于研究实验室的HPLC方法，我们确定万古霉素的平均蛋白结合率为54.6%，与使用基于临床的检测方法的文献报道相比，变异性小得多。此外，我们确定了可能同样影响该值的患者因素。未来关于万古霉素蛋白结合的研究应考虑使用非临床检测方法，以尽量减少方法学引起的变异性。
