基于治疗药物监测的替加环素治疗重症监护病房耐碳青霉烯类革兰阴性菌肺炎的临床疗效及安全性。
Clinical efficacy and safety of tigecycline based on therapeutic drug monitoring for carbapenem-resistant Gram-negative bacterium pneumonia in intensive care units.
机构信息
Department of Pharmacy, Xuan Wu Hospital Capital Medical University, National Gerontic Disease Clinical Research Center, No. 45 Changchun Street, Xi Cheng District, Beijing, 100053, China.
Department of Intensive Medicine, Xuan Wu Hospital Capital Medical University, National Gerontic Disease Clinical Research Center, Beijing, 100053, China.
出版信息
BMC Infect Dis. 2023 Nov 27;23(1):830. doi: 10.1186/s12879-023-08815-7.
BACKGROUND
We investigated the associations between the different doses of tigecycline, its efficacy and safety, and the role of tigecycline therapeutic drug monitoring for patients in the intensive care unit.
METHODS
This study was a single-center cohort including patients infected with multidrug-resistant Acinetobacter baumannii (MDR-AB) and multidrug-resistant Klebsiella pneumoniae (MDR-KP) causing pulmonary infections. The steady-state plasma concentration after tigecycline administration was determined by High-Performance Liquid Chromatography (HPLC) in patients admitted to the ICU between October 2020 and December 2021. Multivariate analyses of tigecycline's clinical efficacy and safety were performed to control confounding factors.
RESULTS
For this study, we included 45 patients and 45 blood samples to determine steady-state trough concentrations of tigecycline. All patients were divided into the High Dose (HD) and Standard Dose (SD) groups. The median trough concentration of tigecycline was 0.56 μg/mL in the HD group, which was higher than in the SD group (0,21 μg/mL), p = 0.000. There was no significant difference between the two groups of patients in terms of bacterial eradication rate, mortality rate, and clinical efficacy. Multiple regression analysis showed that the ICU days were correlated with mortality OR 1.030(1.005-1.056), p = 0.017. APACHE II was significantly associated with clinical efficacy OR 0.870(0.755-1.002), p = 0.045. The level of fibrinogen decline in the HD group was significantly higher than in the SD group (-3.05 ± 1.67 vs -1.75 ± 1.90), p = 0.038. We identified that age and tigecycline treatment duration influenced fibrinogen decline.
CONCLUSIONS
Tigecycline plasma concentrations are significantly increased when using a high dose. However, the plasma concentration of tigecycline is not correlated with clinical efficacy and adverse reactions. Fibrinogen decline appears to be related to the patient's age and days of tigecycline. Large sample data are still needed to confirm the clinical guidance significance of tigecycline TDM.
背景
我们研究了替加环素不同剂量与其疗效和安全性之间的关系，以及替加环素治疗药物监测在重症监护病房患者中的作用。
方法
本研究为单中心队列研究，纳入 2020 年 10 月至 2021 年 12 月期间入住重症监护病房的感染多药耐药鲍曼不动杆菌（MDR-AB）和多药耐药肺炎克雷伯菌（MDR-KP）导致肺部感染的患者。采用高效液相色谱法（HPLC）测定替加环素给药后患者的稳态血浆浓度。采用多变量分析控制混杂因素，评估替加环素的临床疗效和安全性。
结果
本研究共纳入 45 例患者和 45 份血样，以确定替加环素的稳态谷浓度。所有患者均分为高剂量（HD）和标准剂量（SD）组。HD 组替加环素的中位谷浓度为 0.56μg/mL，高于 SD 组（0μg/mL），p=0.000。两组患者的细菌清除率、死亡率和临床疗效无显著差异。多因素回归分析显示，重症监护病房天数与死亡率相关，OR 1.030（1.005-1.056），p=0.017。APACHE II 与临床疗效显著相关，OR 0.870（0.755-1.002），p=0.045。HD 组纤维蛋白原下降水平明显高于 SD 组（-3.05±1.67 比-1.75±1.90），p=0.038。我们发现年龄和替加环素治疗时间影响纤维蛋白原下降。
结论
高剂量使用替加环素时，其血浆浓度显著升高。然而，替加环素的血浆浓度与临床疗效和不良反应无关。纤维蛋白原下降似乎与患者的年龄和替加环素治疗天数有关。仍需要大样本数据来证实替加环素 TDM 的临床指导意义。
Zotero 插件