利奈唑胺谷浓度预测复杂性皮肤软组织感染疗效及血小板减少的回顾性分析

Retrospective Analysis to Estimate Target Trough Concentration of Linezolid for Efficacy and Thrombocytopenia in Patients with Complicated Skin and Soft Tissue Infections

目的探讨接受利奈唑胺治疗的复杂性皮肤软组织感染患者的目标谷浓度对临床疗效和血小板减少的预测价值。方法采用回顾性、单中心、观察性对照研究。收集53例根据微生物学检查或临床情况推断为革兰氏阳性菌感染,并接受利奈唑胺治疗的复杂性皮肤软组织感染患者的临床资料。采用SPSS22.0分析软件进行单因素(t检验,χ~2检验)及多因素Logistic回归分析,比较影响临床疗效及血小板减少的相关因素,绘制ROC曲线并寻找最佳临界值以预测临床特征。结果在有效组和无效组、血小板减少组和正常组之间,利奈唑胺的谷浓度存在显著性差异。多因素Logistic回归分析显示,首次谷浓度是决定利奈唑胺临床疗效和血小板减少的唯一独立变量。临床疗效和血小板减少的ROC曲线下面积分别为0.75和0.76,最佳临界值分别为6.7μg·mL^(-1)(灵敏度97%,特定性67%)和7.5μg·mL^(-1)(灵敏度77%,特异性68%)。结论利奈唑胺谷浓度对临床疗效和血小板减少具有较高的预测价值,通过监测血药浓度制定个体化给药方案可提高临床治愈率,减少药物不良反应。

OBJECTIVE To estimate the target trough concentration in patients with complicated skin and soft tissue infections treated with linezolid and to investigate the predict value of the target trough concentration between clinical efficacy and thrombocytopenia. METHODS In this retrospective, single-center, observational cohort study, 53 hospitalized patients with complicated skin and soft tissue infections who were treated with linezolid due to bacteriologically documented or presumptive Gram-positive infections were extracted. The data were analyzed by t-test, Chi-aquare test(univariate analysis) and Logistic regression analysis(multivariate analysis) using SPSS 22.0 software, the related factors of clinical efficacy and thrombocytopenia were compared. Receiver operating characteristic(ROC) curve was drawn in order to find the best cut-off value to predict clinical feature. RESULTS A significant difference in the first trough concentration of linezolid was observed between the response and non-response groups, and between the thrombocytopenia and non-thrombocytopenia groups. Multiple logistic regression analyses identified the first trough concentration as the only independent variable associated with clinical efficacy and thrombocytopenia of linezolid. The areas under the ROC curves were 0.75 and 0.76 for clinical efficacy and thrombocytopenia, respectively. The cut-off values of the first trough concentration were 6.7 μg·mL-1 for clinical efficacy(sensitivity 97%, specificity 67%) and 7.5 μg·mL-1 for thrombocytopenia(sensitivity 77%, specificity 68%). CONCLUSION These results suggest a relationship of trough linezolid concentration with clinical efficacy and incidence of thrombocytopenia.Serum concentration monitoring is required to achieve best outcomes and the goal of individualized treatment of linezolid.