多黏菌素B在重症感染患者中的应用及其血药浓度分析

Application of polymyxin B in treatment of patients with severe infections and distribution of plasma concentration

    摘要
  • 摘要:
    目的 分析使用多黏菌素B重症感染患者的临床特点, 比较不同肌酐清除率(Ccr)重症感染患者多黏菌素B血药浓度分布情况。
    方法 收集2021年1月-2023年12月东南大学附属中大医院重症医学科(ICU)152例接受静脉用多黏菌素B治疗的重症感染患者的临床信息及其5剂后测定的多黏菌素B谷浓度(Cmin)、中浓度(C1/2t)和峰浓度(Cmax), 根据多黏菌素B药物浓度曲线下面积(AUC0~24 h), 结合三组患者Ccr水平≤30~<60 ml/min组(n=40)、60~<130 ml/min组(n=79)、≥130 ml/min组(n=33)临床信息, 计算多黏菌素B AUC0~24 h的分布情况, 分析患者Ccr对血药浓度的影响。
    结果 152例重症感染患者中, 男性118例, 女性34例, 年龄20~92岁, 基础疾病高血压及糖尿病患者分别占14.47% (22/152)和7.24%(11/152)。多黏菌素B临床主要用于治疗由耐碳青霉烯类鲍曼不动杆菌和肺炎克雷伯菌引起的肺部感染和血流感染。首剂量与维持剂量中位数分别为1.35(1.00, 1.67) mg/kg及1.07(0.83, 1.25) mg/kg q12 h。152例患者多黏菌素B AUC0~24 h为76.57(54.65, 106.47) μg·h/ml, AUC0~24 h在(50~100) μg·h/ml占53.95%(82/152)。虽然三组患者多黏菌数B AUC0~24 h中位数均在(50~100) μg·h/ml, 但Cmin、C1/2t、Cmax和AUC0~24 h在三组间均具有统计学差异(P＜0.05)；此外, 三组患者的多黏菌数B AUC0~24 h在<50 μg·h/ml、(50~100) μg·h/ml及>100 μg·h/ml三个范围内的分布也存在统计学差异(χ2=21.632, P＜0.001)。
    结论 对接受多黏菌素B治疗的重症感染患者进行治疗药物监测(TDM)是有必要的, 特别是Ccr为≤30~<60 ml/min及≥130 ml/min患者。

     

    Abstract:
    OBJECTIVE To analyze the clinical characteristics of the patients with severe infections who were treated with polymyxin B and compare the plasma concentration of polymyxin B among the patients with severe infections with different creatinine clearance rates (Ccr).
    METHODS The clinical data were collected from 152 patients with severe infections who were treated with intravenous polymyxin B in intensive care unit (ICU) of Zhongda Hospital Affiliated to Southeast University from Jan. 2021 to Mar. 2023. The trough concentration (Cmin), median concentration (C1/2t) and peak concentration (Cmax) of polymyxin B were determined after 5 doses were completed. Based of the area under the curve (AUC) of drug concentration of polymyxin B (AUC0~24 h) combined with the Ccr level the ≤30 to<60 ml/min group (n=40), the 60 to<130ml/min group (n=79), and the ≥130ml/min group (n=33), the AUC0~24 h of polymyxin B were calculated, and the influence of Ccr on the plasma concentration was observed.
    RESULTS Among the 152 patients with severe infections, 118 were male, and 34 were female, with the age ranging between 20 and 90 years old; the patients with high blood pressure accounted for 14.47% (22/152), the patients with diabetes mellitus 7.24%(11/152). Polymyxin B is primarily used in clinical settings for the treatment of pulmonary infections and bloodstream infections caused by carbapenem-resistant Acinetobacter baumannii and Klebsiella pneumoniae. The median initial dose and the median maintenance dose were 1.35(1.00, 1.67) mg/kg q12 h and 1.07(0.83, 1.25) mg/kg q12 h, respectively. The median AUC0~24 h of polymyxin B was 76.57(54.65, 106.47)μg·h/ml among the 152 patients, and the patients with AUC0~24 h ranging between 50 and 100 μg·h/ml accounted for 53.95%(82/152). Although the median AUC0~24 hof polymyxin B of all the three groups ranged between 50 and 100)μg·h/ml, there were significant differences in Cmin, C1/2t, Cmax and AUC0~24 h among the three groups(P<0.05). In addition, there were significant differences in the AUC0~24 h of polymyxin B less than 50 μg·h/ml, ranging between 50 and 100 μg·h/ml and more than 100 μg·h/ml among the three groups of patients(χ2=21.632, P<0.001).
    CONCLUSION Therapeutic drug monitoring (TDM) is necessary for the patients with severe infection who receive the polymyxin B for treatment, especially for the patients with Ccr ≤30 to<60 ml/min and Ccr ≥130 ml/min.

     

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