Department of Pharmacy, The Johns Hopkins Hospital, Baltimore, Maryland, USA.
Department of Pharmacy, Indiana University Health, Indianapolis, Indiana, USA.
Surg Infect (Larchmt). 2020 Dec;21(10):859-864. doi: 10.1089/sur.2020.012. Epub 2020 Apr 17.
At a tertiary referral and Level I trauma center, current institutional guidelines suggest initial aminoglycoside doses of gentamicin or tobramycin 4 mg/kg and amikacin 16 mg/kg for patients admitted to surgical intensive care units (SICUs) with suspected gram-negative infection. The objective of this study was to evaluate initial aminoglycoside dosing and peak serum drug concentrations in critically ill surgery patients to characterize the aminoglycoside volume of distribution (V) and determine an optimal standardized dosing strategy. This retrospective, observational, single-center study included adult SICU patients who received an aminoglycoside for additional gram-negative coverage. Descriptive statistics were used to evaluate the patient population, aminoglycoside dosing, and V. Multivariable linear regression was applied to determine variables associated with greater aminoglycoside V. The mortality rate was compared in patients who achieved adequate initial peak concentrations versus those who did not. One hundred seventeen patients received an aminoglycoside in the SICUs, of whom 58 had an appropriately timed peak concentration measurement. The mean Acute Physiology, Age, and Chronic Health Evaluation (APACHE) II score was 27.8 ± 8.9. The V in patients receiving gentamicin, tobramycin, and amikacin was 0.49 ± 0.10, 0.41 ± 0.09, and 0.53 ± 0.13 L/kg, respectively. Together, the mean aminoglycoside V was 0.50 ± 0.12 L/kg. Gentamicin or tobramycin 5 mg/kg achieved goal peak concentrations in 24 patients (63.2%), and amikacin 20 mg/kg achieved the desired concentrations in nine patients (50.0%). Net fluid status, Body Mass Index, and vasopressor use were not predictive of V. There was no difference in the in-hospital mortality rate in patients who achieved adequate peak concentrations versus those who did not (26.8% versus 26.7%; p = 0.99). High aminoglycoside doses are needed in critically ill surgery patients to achieve adequate initial peak concentrations because of the high V. Goal peak concentrations were optimized at doses of gentamicin or tobramycin 5 mg/kg, and amikacin 20 mg/kg.
在一家三级转诊和一级创伤中心，目前的机构指南建议对入住外科重症监护病房（SICU）的疑似革兰氏阴性感染患者给予庆大霉素或妥布霉素 4mg/kg 和阿米卡星 16mg/kg 的初始氨基糖苷类剂量。本研究的目的是评估重症手术患者的初始氨基糖苷类药物剂量和峰血清药物浓度，以描述氨基糖苷类药物分布容积（V）并确定最佳标准化给药策略。这项回顾性、观察性、单中心研究纳入了接受氨基糖苷类药物进行额外革兰氏阴性覆盖的成年 SICU 患者。描述性统计用于评估患者人群、氨基糖苷类药物剂量和 V。多变量线性回归用于确定与更大氨基糖苷类 V 相关的变量。比较了达到适当初始峰浓度的患者与未达到适当初始峰浓度的患者的死亡率。117 名患者在 SICU 接受了氨基糖苷类药物治疗，其中 58 名患者有适当的峰值浓度测量。平均急性生理学、年龄和慢性健康评估 (APACHE) II 评分为 27.8±8.9。接受庆大霉素、妥布霉素和阿米卡星的患者的 V 分别为 0.49±0.10、0.41±0.09 和 0.53±0.13 L/kg。总的来说，氨基糖苷类药物的平均 V 为 0.50±0.12 L/kg。庆大霉素或妥布霉素 5mg/kg 可使 24 名患者（63.2%）达到目标峰浓度，阿米卡星 20mg/kg 可使 9 名患者（50.0%）达到所需浓度。净液体状态、体重指数和血管加压药的使用与 V 无相关性。达到适当峰浓度的患者与未达到适当峰浓度的患者的院内死亡率无差异（26.8% 与 26.7%；p=0.99）。由于 V 较高，重症手术患者需要高剂量氨基糖苷类药物才能达到适当的初始峰浓度。庆大霉素或妥布霉素 5mg/kg 和阿米卡星 20mg/kg 的剂量可优化目标峰浓度。
