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摘要:
目的 分析烧伤患者与肺部感染患者利奈唑胺的药代动力学差异并探讨其影响因素。 方法 该研究为回顾性队列研究。将2024年8月1日—2025年8月1日上海交通大学医学院附属瑞金医院烧伤整形与创面修复科收治的接受利奈唑胺治疗（每12小时给药1次,每次给药600 mg）且完成利奈唑胺血药谷浓度（以下简称血药谷浓度）监测的74例（共行81次血药谷浓度检测）烧伤患者作为烧伤组,其中男22例、女52例,年龄16~87岁。将同期该院重症医学科收治的肺部感染患者中接受相同方案利奈唑胺治疗且完成血药谷浓度监测的74例患者（共行75次血药谷浓度检测）作为肺部感染组,其中男51例、女23例,年龄23~90岁。于第5次给药前30 min,采用液相色谱-串联质谱法检测血药谷浓度。分析烧伤组患者血药谷浓度与年龄、体重、烧伤总面积、Ⅲ度烧伤面积、伤后入院时间、血清白蛋白水平、血清肌酐水平及肌酐清除率之间的相关性,分析肺部感染组患者血药谷浓度与年龄、体重、血清白蛋白水平、血清肌酐水平及肌酐清除率之间的相关性。分析2组患者血药谷浓度与年龄、体重、血清白蛋白水平、血清肌酐水平的交互作用。 结果 烧伤组患者血药谷浓度为2.30（0.65,5.70）mg/L,明显低于肺部感染组的4.07（2.01,7.82）mg/L（Z=-3.131,P<0.05）。烧伤组中血药谷浓度<2 mg/L的患者比例达46.91%（38/81）,明显高于肺部感染组的22.67%（17/75）,χ²=10.030,P<0.05。烧伤组患者血药谷浓度与年龄呈明显正相关（rs=0.483,P<0.05）,与体重及Ⅲ度烧伤面积呈明显负相关（rs值分别为-0.247、-0.231,P<0.05）。肺部感染组患者血药谷浓度与肌酐清除率呈明显负相关（rs=-0.344,P<0.05）,与血清肌酐水平呈明显正相关（rs=0.255,P<0.05）。肺部感染组和烧伤组患者血药谷浓度均仅与血清白蛋白水平存在明显交互作用（β值分别为0.201、-0.145,95%CI分别为-0.085~0.488、-0.344~0.055,P<0.05）。 结论 在利奈唑胺标准给药方案下,烧伤患者血药谷浓度较肺部感染患者显著降低且低血药暴露比例更高。烧伤患者血药谷浓度与年龄、体重及Ⅲ度烧伤面积相关,烧伤患者和肺部感染患者血药谷浓度均与血清白蛋白水平存在明显交互作用。 Abstract:Objective To analyze the pharmacokinetic differences of linezolid between burn patients and patients with pulmonary infection, and to explore the influencing factors. Methods This study was a retrospective cohort study. From August 1st, 2024 to August 1st, 2025, 74 burn patients (with 81 plasma trough concentration measurements) admitted to the Department of Burn of Ruijin Hospital of Shanghai Jiao Tong University School of Medicine, who received linezolid treatment of 600 mg every 12 hours and completed monitoring of plasma trough concentration of linezolid (hereinafter referred to as plasma trough concentration) were included as burn group. There were 22 males and 52 females, aged 16-87 years. During the same period, 74 patients with pulmonary infection (with 75 plasma trough concentration measurements) admitted to the Department of Critical Care Medicine of the same hospital who received the same linezolid treatment and completed monitoring of plasma trough concentration were included as pulmonary infection group. There were 51 males and 23 females, aged 23-90 years. The plasma trough concentrations were detected at 30 min before the fifth administration using liquid chromatography-tandem mass spectrometry. In burn group of patients, the correlations between plasma trough concentration and age, body weight, total burn area, full-thickness burn area, admission time after burn, serum albumin level, serum creatinine level, and creatinine clearance rate were analyzed. In pulmonary infection group of patients, the correlations between plasma trough concentration and age, body weight, serum albumin level, serum creatinine level, and creatinine clearance rate were analyzed. The interactions of plasma trough concentration with age, body weight, serum albumin level, and serum creatinine level between the two groups of patients were analyzed. Results The plasma trough concentration of linezolid in burn group of patients was 2.30 (0.65, 5.70) mg/L, which was significantly lower than 4.07 (2.01, 7.82) mg/L in pulmonary infection group (Z=-3.131, P<0.05). The proportion of patients with plasma trough concentration <2 mg/L in burn group of patients was 46.9% (38/81), which was significantly higher than 22.67% (17/75) in pulmonary infection group (χ²=10.030, P<0.05). In burn group of patients, the plasma trough concentration was significantly positively correlated with age (rs=0.483, P<0.05), and significantly negatively correlated with body weight and full-thickness burn area (with rs of -0.247 and -0.231, respectively, P<0.05). In pulmonary infection group of patients, the plasma trough concentration was significantly negatively correlated with creatinine clearance rate (rs=-0.344, P<0.05), and significantly positively correlated with serum creatinine level (rs=0.255, P<0.05). Both in pulmonary infection group and burn group of patients, the plasma trough concentration showed a significant interaction with the serum albumin level (with β values of 0.201 and -0.145, respectively, 95%CI of -0.085 to 0.488 and -0.344 to 0.055, respectively, P<0.05). Conclusions Under the standard dosing regimen of linezolid, the plasma trough concentration in burn patients was significantly lower than that in patients with pulmonary infection, and the proportion of low drug exposure was higher. In burn patients, the plasma trough concentration was correlated with age, body weight, and full-thickness burn area. Both in burn patients and patients with pulmonary infection, the plasma trough concentration showed a significant interaction with serum albumin level. -
Key words:
- Burns /
- Pharmacokinetics /
- Linezolid /
- Plasma trough concentration /
- Precision medicine
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参考文献
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图 1 2组患者利奈唑胺血药谷浓度与其影响因素的交互作用森林图
注：肺部感染组74例患者共进行75次血药谷浓度检测,烧伤组74例患者共进行81次血药谷浓度检测；于利奈唑胺第5次给药前30 min检测血药谷浓度及血清肌酐、白蛋白水平
Table 1. 2组行利奈唑胺治疗的患者的一般资料比较[M（Q1,Q3）]
组别 例数 年龄（岁） 体重（kg） 肌酐清除率（mL/min） 血清肌酐水平（μmol/L） 血清白蛋白水平（g/L） 烧伤组 74 45.5（34.0,60.0） 66.0（59.3,75.8） 64.00（51.50,95.42） 102.00（67.39,140.28） 33.00（30.00,37.50） 肺部感染组 74 72.0（63.8,81.0） 61.0（50.0,70.0） 79.42（39.90,105.52） 71.00（50.00,98.00） 31.00（28.00,33.00） Z值 -6.805 -2.872 -0.625 -3.340 -4.011 P值 <0.001 0.004 0.532 <0.001 <0.001 注：于利奈唑胺第5次给药前30 min检测血清肌酐、白蛋白水平并计算肌酐清除率；烧伤组患者共进行81次检测,肺部感染者组患者共进行75次检测 
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Table 2. 2组患者利奈唑胺血药谷浓度分布
组别 例次 <2 mg/L 2~8 mg/L >8 mg/L 烧伤组 81 38（46.91%） 28（34.57%） 15（18.52%） 肺部感染组 75 17（22.67%） 43（57.33%） 15（20.00%）
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Table 3. 烧伤组患者利奈唑胺血药谷浓度与其影响因素之间的相关性
影响因素 rs值 P值 年龄（岁） 0.483 <0.001 体重（kg） -0.247 0.026 烧伤总面积（TBSA%） -0.177 0.114 Ⅲ度烧伤面积（TBSA%） -0.231 0.038 伤后入院时间（d） 0.100 0.374 血清白蛋白水平（g/L） -0.151 0.178 血清肌酐水平（μmol/L） -0.139 0.217 肌酐清除率（mL/min） -0.151 0.179 注：74例患者共进行81次血药谷浓度检测；于利奈唑胺第5次给药前30 min检测血药谷浓度及血清肌酐、白蛋白水平并计算肌酐清除率；TBSA为体表总面积
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Table 4. 肺部感染组患者利奈唑胺血药谷浓度与其影响因素之间的相关性
影响因素 rs值 P值 年龄（岁） 0.225 0.052 体重（kg） -0.130 0.267 血清白蛋白水平（g/L） 0.164 0.159 血清肌酐水平（μmol/L） 0.255 0.027 肌酐清除率（mL/min） -0.344 0.002 注：74例患者共进行75次血药谷浓度检测,于利奈唑胺第5次给药前30 min检测血药谷浓度及血清肌酐、白蛋白水平并计算肌酐清除率
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