Department of Pharmacy, National Hospital Organization Osaka National Hospital, Osaka, Japan.
Intensive Care Med. 2013 Jul;39(7):1247-52. doi: 10.1007/s00134-013-2909-9. Epub 2013 Apr 20.
Vancomycin has been used in patients with sepsis infected by MRSA and shows large interindividual variability in its dosing. In this observational study the potential influence of sepsis status on the vancomycin dose requirement in relation to systemic inflammatory response syndrome (SIRS) criteria was assessed.
From about 250 patients receiving serum vancomycin monitoring from May 2006 to April 2011 at the Osaka National Hospital, 105 adult patients who had been assessed using the SIRS criteria were identified. Patients on chemotherapy or intermittent positive pressure ventilation in whom the SIRS criteria could not accurately evaluate inflammatory status were excluded. Using two vancomycin serum concentrations at peak and trough, individual pharmacokinetic parameters were calculated by the Bayesian estimation method using a two-compartment model. Creatinine clearance rate was estimated by the Cockcroft-Gault formula (eCcr).
Patients with SIRS had a significantly higher vancomycin clearance than those without SIRS, indicating that SIRS patients had a higher elimination capacity. The vancomycin clearance was positively correlated with the SIRS score defined as the number of positive items in the criteria, and negatively with age, except in patients with renal dysfunction. A linear relationship between the vancomycin clearance and eCcr remained even in the supernormal eCcr phase (more than approximately 120 mL/min).
This study provides a new insight into the need for quick prediction of dose requirement. That is, an increased vancomycin dosage would be needed in patients with a higher SIRS score to maintain the therapeutic target concentration, in particular in those with a high eCcr value.
万古霉素已被用于治疗感染耐甲氧西林金黄色葡萄球菌(MRSA)的脓毒症患者,其剂量在个体间存在较大差异。在这项观察性研究中,评估了脓毒症状态对万古霉素剂量需求的潜在影响,特别是与全身炎症反应综合征(SIRS)标准的关系。
从 2006 年 5 月至 2011 年 4 月在大阪国立医院接受血清万古霉素监测的约 250 名患者中,选择了 105 名符合 SIRS 标准的成年患者。排除接受化疗或间歇性正压通气的患者,因为这些患者的 SIRS 标准无法准确评估炎症状态。使用峰和谷时的两个万古霉素血清浓度,通过贝叶斯估计法使用两室模型计算个体药代动力学参数。肌酐清除率通过 Cockcroft-Gault 公式(eCcr)估计。
患有 SIRS 的患者的万古霉素清除率明显高于未患有 SIRS 的患者,表明 SIRS 患者具有更高的消除能力。万古霉素清除率与 SIRS 评分呈正相关,SIRS 评分定义为标准中阳性项目的数量,与年龄呈负相关,但在肾功能不全的患者中除外。即使在超正常 eCcr 阶段(超过约 120 mL/min),万古霉素清除率与 eCcr 之间仍存在线性关系。
本研究为快速预测剂量需求提供了新的见解。即,对于 SIRS 评分较高的患者,需要增加万古霉素剂量以维持治疗目标浓度,特别是对于 eCcr 值较高的患者。