目的 评价万古霉素负荷剂量对重症患者血万古霉素24小时药时曲线下面积（AUC₂₄）的影响。方法 回顾分析2015年1月-2017年9月入住广州医科大学附属第二医院重症医学科的319例临床怀疑或证实存在严重的革兰阳性球菌感染的重症患者，根据医嘱中是否使用万古霉素25 mg/kg体质量的负荷剂量，将患者分为普通用药组和负荷剂量组，计算万古霉素的AUC₂₄>400为目标AUC₂₄。通过多元线性逐步回归法和Logistic回归进行多因素分析。生存分析采用Kaplan-Meier法进行分析。结果 负荷剂量组纳入患者68例，普通用药组纳入患者156例。普通用药组AUC₂₄明显低于负荷剂量组，两者比较差异具有显著意义（P<0.001）；负荷剂量和普通用药组患者住院死亡率存在差异，分别为20.59%、35.26%。将多因素纳入Logistic回归方程分析后发现，使用万古霉素负荷剂量患者的死亡率为普通用药组的47.80%。Kaplan-Meier生存分析提示两者生存曲线比较差异存在显著差异（P=0.02）。结论 用万古霉素25 mg/kg负荷剂量给药方案能有效提高临床怀疑或证实存在严重的革兰阳性球菌感染重症感染患者万古霉素AUC₂₄的水平和达标率，同时降低ICU住院死亡率。

Objective To evaluate the effect of vancomycin loading dose on the area under 24-hour curve (AUC₂₄) of vancomycin in critical patients. Methods A retrospective analysis was made on 319 patients with suspected or confirmed severe Gram-positive coccal infections who were admitted to Department of Intensive Care Unit, The Second Affiliated Hospital of Guangzhou Medical University from January 2015 to September 2017. According to the loading dose of vancomycin with 25 mg/kg body weight, patients were divided into general administration group and loading dose group. The target AUC₂₄ was set as AUC₂₄ > 400. Kaplan-Meier method was used for survival analysis. Multivariate linear stepwise regression and logistic regression were used for multivariate analysis. Results There were 68 patients in loading dose group and 156 patients in general administration group. AUC₂₄ of general administration group were lower than that of loading dose group with significant difference (P < 0.001). There were differences in ICU mortality between two groups, which were 20.59% and 35.26%, respectively. Multivariate logistic regression analysis showed that the mortality rate of loading dose group was 47.80% compared with general administration group. Kaplan-Meier survival analysis indicated that there was significant difference in survival curve between two groups (P=0.02). Conclusion Vancomycin dosages with loading dose can improve the levels of vancomycin AUC₂₄ and the rate of reaching the standard in patients with suspected or confirmed severe Gram-positive coccal infections and reduce the in-hospital mortality in ICU.

R978.1

广东省医院药学研究基金资助项目（2016A30）