Denetclaw Tina Harrach, Dowling Thomas C, Steinke Douglas
Marin General Hospital, Greenbrae, CA, USA.
Ann Pharmacother. 2013 Dec;47(12):1611-7. doi: 10.1177/1060028013510395. Epub 2013 Oct 25.
Current guidelines recommend vancomycin trough concentrations 15 to 20 µg/mL in complicated infections and all trough concentrations above 10 µg/mL.
We assessed the performance of a novel divided-load protocol designed to attain target trough concentrations within 24 hours of initiation and prevent doses given at concentrations above the target range, in critically ill patients.
The protocol was evaluated in 79 critically ill patients through retrospective medical record review. Vancomycin serum concentrations were drawn before the third dose after initiation and after any dosing change. Steady-state concentrations were drawn before the fifth or sixth doses. Vancomycin concentrations before the second dose were predicted using a nonparametric expectation maximization algorithm.
Sixty-nine of 79 patients received scheduled doses, and 62 (90%) of the scheduled-dose patients attained therapeutic target concentrations 12 to 24 hours after therapy initiation. Eight scheduled-dose patients weighed > 150% of ideal body weight (IBW) and were significantly more likely to exhibit supratherapeutic trough concentrations before the fifth or sixth doses (P = .0004) compared with patients weighing ≤150% of IBW. Ten of 79 patients (8 dialysis dependent and 2 experiencing acute kidney injury) were dosed in response to measured serum drug concentrations drawn according to the divided-load protocol. All the 8 dialysis-dependent patients (100%) attained therapeutic concentrations 12 hours after therapy initiation.
The divided-load vancomycin dosing strategy achieved measured trough concentrations 15 to 20 µg/mL for most critically ill patients within 24 hours of initial dosing, without allowing doses given during supratherapeutic concentrations.
当前指南建议，在复杂感染中万古霉素谷浓度为15至20μg/mL，所有谷浓度应高于10μg/mL。
我们评估了一种新型的分次负荷方案的效果，该方案旨在使重症患者在开始治疗后24小时内达到目标谷浓度，并防止在高于目标范围的浓度下给药。
通过回顾性病历审查对79例重症患者的该方案进行评估。在开始治疗后的第三剂之前以及任何剂量改变之后采集万古霉素血清浓度。在第五或第六剂之前采集稳态浓度。使用非参数期望最大化算法预测第二剂之前的万古霉素浓度。
79例患者中有69例接受了预定剂量，62例（90%）接受预定剂量的患者在开始治疗后12至24小时达到了治疗目标浓度。8例接受预定剂量的患者体重超过理想体重（IBW）的150%，与体重≤IBW 150%的患者相比，这些患者在第五或第六剂之前出现超治疗谷浓度的可能性显著更高（P = 0.0004）。79例患者中有10例（8例依赖透析，2例发生急性肾损伤）根据分次负荷方案采集的实测血清药物浓度进行给药。所有8例依赖透析的患者（100%）在开始治疗后12小时达到了治疗浓度。
分次负荷万古霉素给药策略在初始给药后24小时内使大多数重症患者的实测谷浓度达到15至20μg/mL，且未出现超治疗浓度下的给药情况。
