替考拉宁药代动力学指导重症G^+菌感染患者个体化用药的临床分析

Clinical study of Teicoplanin pharmacokinetics on individual therapy in patients with severe G^+ coccus infection

目的探讨替考拉宁药代动力学指导个体化用药在重症G^+感染患者中的优势。方法选取西部战区总医院确诊为重症G^+感染患者80例,随机分成替考拉宁标准组与优化组各40例。用高效液相色谱法(HPLC)进行血药浓度监测(TDM)。标准组按说明书给药,优化组在药代动力学指导下个体化给药。比较两组患者第3、6剂谷浓度及目标谷浓度达标率、AUC0-24/MIC≥125、345的达标率、第1、4天体温、炎性指标、细菌清除率、结局指标、药物不良反应等,评价其疗效及安全性。结果 HPLC法标准曲线方程式:Y=14.316X+2.881 (r2=0.9999,n=6)。与标准组比较,优化组第6剂谷浓度及达标率更高(11.16±3.16 mg/L vs. 8.96±4.10 mg/L,82.5%vs. 32.5%,P<0.05); AUC0-24/MIC≥345达标率更优(67.5%vs. 27.5%,P<0.05);第1、4天WBC、CRP下降更快;细菌清除率更佳(80%vs. 55%,P<0.05);治疗总有效率更好(85%vs. 65%,P<0.05)。与谷浓度密切相关的是给药剂量(kg,mg/kg)和肌酐清除率(CLcr,ml/min)。拟合方程式:Log C3=0.405+0.068 kg3-0.001 CLcr3(VIF 1.023,R2=61.8%,P<0.001),Log C6=0.92+0.042 kg6-0.004 CLcr6(VIF 1,R2=73.5%,P<0.001)。结论 HPLC法进行TDM准确、可靠。替考拉宁药代动力学指导的个体化用药治疗重症G^+感染患者疗效高,安全性好。拟合方程式可为临床用药提供参考。

Objective To detect the relationship between the plasma concentration of teicoplanin and the influencing factors and to explore the advantage of individual treatment of the severe Gram-positive coccus infection under pharmacokinetic guidance. Methods Eighty patients with confirmed severe Gram-positive coccus infection from the General Hospital of Western Theater Command were randomly divided into the standard group and the optimized group. Therapeutic Drug Monitoring(TDM) was conducted by High Performance Liquid Chromatography(HPLC). The dosage regimen of teicoplanin was adopted in accordance with the drug instruction in the standard group, whereas the optimized group was applied personalized dosage regimen guided by the pharmacokinetics. The targeted trough concentration at the 3^rd dose and the 6 th dose and its success rate, the success rate of AUC 0-24 /MIC≥125 and AUC 0-24 /MIC≥345, some clinical and lab parameters, clinical outcome were compared between two groups. Results The teicoplanin standard curve for the equation was Y=14.316X+2.881( r^2=0.9999, n =6). The trough concentration and the success rate at the 6 th dose in the optimized group were significantly higher than that in the standard group [(11.16±3.16 vs. 8.96± 4.10)mg/L, 82.5% vs. 32.5%, P <0.05]. The optimized group had a better success rate of AUC 0-24 /MIC≥345 than the standard group (67.5% vs. 27.5%, P <0.05). The white blood cell and CRP in the optimized group improved apparently when compared with the standard group. When compared with the standard group, the optimized group had a higher bacterial clearance rate (80% vs. 55%, P <0.05) and whole effective rate (85% vs. 65%, P <0.05). The factors affected the teicoplanin trough concentration were creatinine clearance rate (CLcr, ml/min) and the loading dose (kg, mg/kg) and the best multiple regression model was as follows: LogC3=0.405+0.068 kg3-0.001 CLcr3 ( VIF 1.023, R^2=61.8%, P <0.001), LogC6=0.92+0.042 kg6 -0.004 CLcr 6 ( VIF1, R^2=73.5%, P <0.001). Conclusion HPLC is worthy of teicoplanin TDM with its accuracy and reliability. Individual medication guided by the teicoplanin pharmacokinetics improves the therapeutic efficacy and the safety of patients with severe Gram-positive infection and the fitting equation provides a reference for clinical use.