Children's and Women's Health Centre of British Columbia, Vancouver, BC, Canada.
Paediatr Drugs. 2015 Jun;17(3):245-53. doi: 10.1007/s40272-015-0122-8.
Pediatric studies and anecdotal experience suggest that current empiric vancomycin dosing does not reach serum trough concentration targets of at least 10 mg/L for uncomplicated infections or 15-20 mg/L for serious or complicated infections.
This study reviewed vancomycin dosing and serum concentrations to (i) determine the proportion of patients who reached initial target concentrations; (ii) describe pharmacokinetic parameters; and (iii) compare patient-specific area-under-the-curve (AUC) values to population estimates using the Rodvold equation.
Following ethics approval, data were extracted from medical records of 200 patients aged 1 month-18 years, who received intravenous (IV) vancomycin and had at least two pharmacokinetically evaluable serum concentrations.
Trough vancomycin concentrations of 10-15 and 15-20 mg/L were achieved in 25 (29%) and 2 (2%) patients receiving vancomycin 15 mg/kg IV every 6 h (q6 h) and 22 (20%) and 9 (8%) patients receiving vancomycin 20 mg/kg IV every 8 h (q8 h), respectively. Patients were stratified into four age groups (1 month-1 year, 1-6 years, 6-13 years and 13-18 years). Median (IQR) pharmacokinetic parameters were elimination rate constant 0.25 (0.09), 0.29 (0.07), 0.24 (0.10) and 0.22 (0.07) h(-1); volume of distribution 0.56 (0.20), 0.61 (0.21), 0.47 (0.26) and 0.49 (0.22) L/kg; and half-life 2.8 (1.1), 2.4 (0.5), 2.9 (1.1) and 3.2 (1.0) h, respectively. Median (IQR) AUCs were 458 (170), 338 (132), 478 (215) and 513 (179) mg h/L and population-estimated AUCs were 67 (44), 108 (70), 299 (102) and 454 (103) mg h/L (p < 0.05 for all groups).
Based on these findings, we recommend vancomycin 70 and 90 mg/kg/day divided q6 h for troughs of 10-15 and 15-20 mg/L, respectively (patients 1 month-6 years) and 60 mg/kg/day divided q8 h and 70 mg/kg/day divided q6 h, respectively (patients >6 years) to undergo further testing as initial dosing regimens. Furthermore, population estimates grossly underestimate vancomycin AUC in patients 1-18 years old and thus patient-specific parameters are required.
儿科研究和轶事经验表明，目前经验性万古霉素给药方案并未达到 10 毫克/升（mg/L）以下的单纯感染或 15-20mg/L 的严重或复杂感染的血清谷浓度目标。
本研究回顾了万古霉素的给药和血清浓度，以：（i）确定达到初始目标浓度的患者比例；（ii）描述药代动力学参数；（iii）使用 Rodvold 方程比较患者特定的 AUC 值与人群估计值。
在获得伦理批准后，从 200 名 1 个月至 18 岁接受静脉（IV）万古霉素治疗且至少有两个可进行药代动力学评估的血清浓度的患者的病历中提取数据。
接受 15mg/kg IV 每 6 小时（q6 h）万古霉素治疗的患者中，有 25 名（29%）达到 10-15mg/L 的谷浓度，2 名（2%）达到 15-20mg/L 的谷浓度；接受 20mg/kg IV 每 8 小时（q8 h）万古霉素治疗的患者中，有 22 名（20%）达到 10-15mg/L 的谷浓度，9 名（8%）达到 15-20mg/L 的谷浓度。患者分为四个年龄组（1 个月至 1 岁、1-6 岁、6-13 岁和 13-18 岁）。中值（IQR）药代动力学参数为消除率常数 0.25（0.09）、0.29（0.07）、0.24（0.10）和 0.22（0.07）h（-1）；分布容积 0.56（0.20）、0.61（0.21）、0.47（0.26）和 0.49（0.22）L/kg；半衰期 2.8（1.1）、2.4（0.5）、2.9（1.1）和 3.2（1.0）h，分别。中值（IQR）AUC 为 458（170）、338（132）、478（215）和 513（179）mg h/L，人群估计 AUC 为 67（44）、108（70）、299（102）和 454（103）mg h/L（所有组均 p<0.05）。
根据这些发现，我们建议对于 1 个月至 6 岁的患者，将万古霉素剂量分别调整为 70mg/kg/天和 90mg/kg/天，每 6 小时给药一次，以达到 10-15mg/L 和 15-20mg/L 的谷浓度；对于 6 岁以上的患者，将万古霉素剂量分别调整为 60mg/kg/天和 70mg/kg/天，每 8 小时给药一次，作为初始给药方案进行进一步测试。此外，人群估计值严重低估了 1-18 岁患者的万古霉素 AUC，因此需要患者特定的参数。
