目的:观察重症患者不同给药方案下万古霉素药代动力学-药效动力学（PK-PD）参数的变化特点，并对其影响因素进行深入探讨。方法:回顾性分析2011年1月至2018年12月上海交通大学医学院附属瑞金医院重症监护病房（ICU）使用过万古霉素并有稳态谷浓度（Cn min）测定数据患者的临床资料。根据万古霉素的给药间隔将患者分成q12 h组（12 h给药1次）、q8 h组（8 h给药1次）、q6 h组（6 h给药1次），收集患者万古霉素Cn min，采用Bayesian法估算万古霉素用药前（0 h）及用药后1、2、4、6、8、12和24 h的血药浓度，采用梯形面积法估算万古霉素24 h内血药浓度-时间曲线下面积（AUCn 0～24 h）；收集同期病原微生物对万古霉素的最低抑菌浓度（MIC），计算AUCn 0～24 h/MIC。n 结果:共收集到285例患者529项Cn min数据，其中q12 h组375项，q8 h组121项，q6 h组33项。使用JPKD-Ver 3.1软件统一日剂量后，q12 h组、q8 h组、q6 h组万古霉素目标谷浓度达标率（Cn min为10～20 mg/L）分别为35.7%、43.8%、60.6%，但是仅q12 h组与q6 h组比较差异具有统计学意义（n P<0.01）；q6 h组、q8 h组较q12 h组具有较高的Cn min（mg/L：13.8±5.2、13.5±7.3比11.4±7.9，均n P<0.05）及较低的峰浓度〔Cn max（mg/L）：19.4±5.3、21.5±7.3比23.9±8.1，均n P0.05）。多元线性回归分析显示，肌酐清除率（CCr）、万古霉素清除率（CLn 万古）是影响万古霉素Cn min及AUCn 0～24 h/MIC等PD指标的主要因素（CCr的n r值分别为-0.391、-0.424，CLn 万古的n r值分别为-0.673、-0.663，均n P<0.01），且均与年龄呈负相关（n r值分别为-0.432、-0.488，均n P<0.01）。n 结论:相同日剂量下，增加万古霉素给药频率可提高Cn min并降低Cn max，从而降低血药浓度的波动性，但不影响AUCn 0～24 h/MIC。应根据CCr、CLn 万古以及年龄等参数优化重症患者万古霉素的给药方案。n “,”Objective:To observe the changing characteristics of pharmacokinetic and pharmacodynamic (PK-PD) parameters of vancomycin in critical patients under different drug regimens and to further explore the influencing factors.Methods:The clinical data of patients who treated with vancomycin and recorded by steady-state through concentration (Cn min) admitted to intensive care unit (ICU) of Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine from January 2011 to December 2018 were analyzed retrospectively. The patients were divided into three groups according to the dosing interval (groups of q12 h, q8 h and q6 h respectively) and Cn min was collected. The serum concentration of vancomycin before (0 hour) and 1, 2, 4, 6, 8, 12 and 24 hours after administration were estimated by JPKD Ver 3.1. Area under the curve (AUCn 0-24 h) was estimated by trapezoidal area method. Minimum inhibitory concentration (MIC) of pathogenic microorganisms in the same period was retrieved, thus AUCn 0-24 h/MIC was calculated.n Results:285 patients with 529 records of Cn min were enrolled in the study, including 375 data in q12 h group, 121 data in q8 h group and 33 data in q6 h group. After unifying daily dose by JPKD Ver 3.1, the Cn min (10-20 mg/L) reaching rate of q12 h group, q8 h group, q6 h group were 35.7%, 43.8% and 60.6%, respectively, while only q12 h group was statistically significant compared with q6 h group (n P < 0.01). q6 h group and q8 h group showed higher C n min than q12 h group (mg/L: 13.8±5.2, 13.5±7.3 vs. 11.4±7.9, both n P < 0.05) and lower peak concentration (C n max) than q12 h group (mg/L: 19.4±5.3, 21.5±7.3 vs. 23.9±8.1, both n P 0.05). Multiple linear regression analysis showed that creatinine clearance (CCr) and vancomycin clearance (CLvancomycin) were the main influencing factors of vancomycin PD parameters such as C n min and AUCn 0-24 h/MIC (n r values of CCr were -0.391, -0.424, and rvalues of CLvancomycin were -0.673, -0.663, all n P < 0.01), and were negatively correlated with age ( n r values were -0.432 and -0.488, respectively, both n P < 0.01).n Conclusions:At the same daily dose, Cn min can be increased and Cn max can be decreased by increasing the frequency of vancomycin administration, thus minimize the fluctuation of vancomycin serum concentration, but AUCn 0-24 h/MIC is not affected. Vancomycin administration regimen in severe patients should be optimized according to CCr, CLvancomycin and age.n