Safety and Efficacy of Tigecycline in Intensive Care Unit Patients Based on Therapeutic Drug Monitoring
Safety and Efficacy of Tigecycline in Intensive Care Unit Patients Based on Therapeutic Drug Monitoring
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DOI：
10.1097/ftd.0000000000000784
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发表时间：
2020-12-01
影响因子：
2.5
通讯作者：
Dong, Yalin
中科院分区：
文献类型：
--
作者：
Fan, Guangjun;Jin, Liu;Dong, Yalin
目的：替加环素对耐药细菌感染具有显著的治疗作用。临床实践中使用的主要是经验性药物，通常与疗效和安全性的广泛个体差异有关。我们调查了替加环素的药代动力学及其在重症监护病房（ICU）患者的疗效和安全性之间的关联，目的是促进替加环素的临床应用。通过单变量和多变量analysis.Results：本研究包括45例患者，共收集了63份血液样本，以确定替加环素的稳态血浆谷浓度（C-min）的临床疗效和安全性的相关因素进行了评估。替加环素的C-min为417.1 ± 263.8 ng/mL（平均6 SD）。多因素分析显示，APACHE II评分[OR = 0.874，95%可信区间（CI）= 0.733-0.901，P = 0.048]与替加环素疗效显著相关，而替加环素C-min与疗效无相关性。在安全性方面，与肝毒性显著相关的危险因素是性别（OR = 0.562，95%CI = 0.191-0.774，P = 0.023），APACHE Ⅱ评分（OR = 1.061，95%CI = 1.039-1.392，P = 0.045）和C-min（OR = 1.210，95%CI = 1.014-1.336，P = 0.008）。在ICU患者中用替加环素治疗的肝毒性的最佳截止值为474.8 ng/mL.Conclusions：在本研究中，ICU患者中替加环素的C-min存在相当大的变异性，并且在女性中存在高暴露风险。C-min可以作为肝毒性的有用预测因子，临界值为474.8 ng/mL。
Objective: Tigecycline exerts significant beneficial effects against drug-resistant bacterial infections. The largely empirical medications used in clinical practice are often associated with wide individual differences in efficacy and safety. We investigated the associations between the pharmacokinetics of tigecycline and its efficacy and safety in intensive care unit (ICU) patients, with the aim of facilitating clinical applications of tigecycline.Methods: ICU patients who were prescribed tigecycline in a hospital setting were prospectively included. Factors related to the clinical efficacy and safety of tigecycline were assessed by univariate and multivariate analyses.Results: This study included 45 patients, from whom a total of 63 blood samples were collected to determine steady-state trough plasma concentrations (C-min) of tigecycline. The C-min of tigecycline was 417.1 6 263.8 ng/mL (mean 6 SD). The multivariate analysis showed that the APACHE II scores [odds ratio (OR) = 0.874, 95% confidence interval (CI) = 0.733-0.901, P = 0.048] were significantly correlated with the efficacy of tigecycline, whereas there was no correlation between C-min of tigecycline and efficacy. In safety, the risk factors significantly associated with hepatotoxicity were sex (OR = 0.562, 95% CI = 0.191-0.774, P = 0.023), APACHE II score (OR = 1.061, 95% CI = 1.039-1.392, P = 0.045), and C-min (OR = 1.210, 95% CI = 1.014-1.336, P = 0.008). The optimal cut-off for hepatotoxicity in ICU patients treated with tigecycline was 474.8 ng/mL.Conclusions: There was considerable variability in the C-min of tigecycline among the ICU patients in this study and it is at risk of high exposure in women. C-min can be a useful predictor of hepatotoxicity with a cut-off of 474.8 ng/mL.