万古霉素治疗儿童MRSA肺炎的体内暴露量与临床疗效研究

Relationship between in vivo exposure of vancomycin and clinical efficacy in children with MRSA pneumonia

目的研究万古霉素治疗儿童耐甲氧西林金黄色葡萄球菌(MRSA)肺炎的体内暴露量与临床疗效的关系。方法选取2014年1月-2018年5月华中科技大学同济医学院附属武汉儿童医院使用万古霉素治疗MRSA肺炎的155例为研究对象,观察万古霉素的临床疗效并测定万古霉素的体内暴露指标,包括:血清峰浓度(Cmax)、谷浓度(Cmin)、给药24 h内药-时曲线下面积与最低抑菌浓度的比值(AUC24h/MIC)以及给药周期内药-时曲线下面积与最低抑菌浓度的比值(AUCτ/MIC)。采用受试者工作特征(ROC)曲线考察上述暴露指标与临床疗效的关联性。建立Logistic回归方程评估万古霉素在不同暴露水平下治疗儿童MRSA肺炎的成功概率。结果本研究中万古霉素治疗儿童MRSA肺炎的总有效率为41.3%;AUC24h/MIC与临床疗效的关联性最强,ROC曲线下面积为0.874;当约登指数(Youden index)最大时对应的ROC曲线上最佳AUC24h/MIC界值切点为377.5,高于该值时预示抗感染治疗成功率较高。结论 AUC24h/MIC是预测万古霉素治疗儿童MRSA肺炎疗效的最佳暴露指标,临床应根据该指标调整用药方案。

OBJECTIVE To investigate the relationship between in vivo exposure of vancomycin and clinical efficacy in children with pneumonia caused by methicillin-resistant Staphylococcus aureus(MRSA). METHODS A total of 155 patients(aged 1 month to 16 years old) with MRSA pneumonia treated using vancomycin in our hospital from Jan. 2014 to May 2018 were selected as the research objects. The clinical efficacy of vancomycin was observed and the in vivo exposure indexes were determined, including serum peak concentration(Cmax), trough concentration(Cmin), the ratio of the area under the drug concentration-time curve in a 24-h interval to the minimum inhibitory concentration(AUC24 h/MIC), and the ratio of the area under the drug concentration-time curve in a dosing interval to the minimum inhibitory concentration(AUCτ/MIC). The correlation between the vancomycin exposure indexes above and clinical efficacy was evaluated with receiver operating characteristic(ROC) curve analysis. Logistic regression equation was established to evaluate the effective probability of vancomycin in treating children with MRSA pneumonia at different exposure levels. RESULTS In this study, the total effective rate of vancomycin in the treatment of MRSA pneumonia in children was 41.3%. ROC curve analysis suggested that the AUC24 h/MIC had the best correlation with clinical efficacy, and the area under the ROC curve was 0.874. The best cut-off value of AUC24 h/MIC was 377.5, then the Youden index was the largest. It indicated that the effective probability of anti MRSA infective treatment would be much higher when AUC24 h/MIC was above 377.5. CONCLUSION AUC24 h/MIC is the best exposure indicator to predict the efficacy of vancomycin in the treatment of MRSA pneumonia in children, so the dosage regimens of vancomycin should be adjusted according to this index.