万古霉素AUC/MIC在多重耐药革兰阳性菌致重症感染中的应用分析

目的：探讨以药时曲线下面积（AUC）/最低抑菌浓度（MIC）作为万古霉素监测靶目标在我院多重耐药革兰阳性菌致重症感染患者中的应用情况和临床意义。方法：以确诊多重耐药革兰阳性菌感染的患者为研究对象，通过监测患者万古霉素的血药谷浓度（Ct），借助药代动力学软件Java PK for Desktop（JPKD）采用贝叶斯计算方法计算万古霉素药时AUC，并计算AUC24h/MIC的值（假设MIC=1 mg/L）。比较不同Ct范围内AUC24h/MIC的达标率，分析AUC24h/MIC的影响因素并探讨以AUC24h/MIC作为靶目标对患者抗感染疗效和肾毒性的临床意义。结果：多元线性回归分析显示Ct与AUC24h/MIC有较好的相关性，当Ct为10～15 μg/mL时，其中仅38.89%的患者AUC24h/MIC达到400～600，当Ct为15～20 μg/mL时，则有88.89%患者其AUC24h/MIC达标。万古霉素抗感染疗效与患者是否入住ICU显著相关，而与AUC24h/MIC无显著相关性。以Ct＞20 μg/mL或者AUC24h/MIC＞600评估发生急性肾损伤（AKI）的风险无统计学差异。结论：假设MIC=1 mg/L时建议多重耐药革兰阳性菌致严重感染患者维持Ct在15～20 μg/mL，有88.89%概率其AUC24h/MIC可达到400～600。为了更好地指导临床合理使用万古霉素，建议推广MIC的规范化检测。

Application of AUC/MIC as the therapeutic drug monitoring target of vancomycin in patients with severe infections of multi drug resistant gram positive bacteria

AIM: To discuss the application and clinical significance of the ratio of area under the curve over 24 hours to minimum inhibitory concentration (AUC24h/MIC) as the monitoring target of vancomycin in patients with severe infections of multi drug resistant gram positive bacteria (MDR G+bacteria) in our hospital. METHODS: All patients with MDR G+bacterial infections were performed serum trough concentration of vancomycin (Ct). We used the pharmacokinetic software JPKD and Bayesian calculation to estimate the AUC24h/MIC of vancomycin (if MIC=1 mg/L). Then we compared the attainment rates of AUC24h/MIC with different Ct range, and tried to find out the probable interfering factors that might affect AUC24h/MIC and the clinical significance to take AUC24h/MIC as a predictor of curative effect and nephrotoxicity. RESULTS: Multiple linear regression analysis showed Ct had a good correlation with AUC24h/MIC. When Ct was 10-15 μg/mL, only 38.89% of the patients performed AUC24h/MIC 400-600, but when Ct was 15-20 μg/mL, up to 88.89% of the patients could achieve the recommended range. The curative effect of vancomycin seemed to have a significant correlation with patients accepting intensive care or not, rather than AUC24h/MIC. Whether use Ct＞20 μg/mL or AUC24h/MIC＞600 as an indicator to evaluate the occurrence risk of acute kidney injury(AKI) showed no differences. CONCLUSION: Patients with MDR G+bacterial infections should maintain Ct between 15-20 μg/mL, in this case, there was 88.89% probability to achieve AUC24h/MIC of 400-600. Also, the standardized testing of MIC should be proposed to improve the clinical application of vancomycin.