药代动力学指导下应用替考拉宁治疗重症革兰阳性球菌感染

Clinical value of teicoplanin in the treatment of severe gram-positive cocci infection under the guidance of pharmacokinetics

目的研究药代动力学指导下应用替考拉宁治疗重症革兰阳性球菌感染的临床价值。方法选取郑州大学附属郑州中心医院2019年1月-2019年12月收治并确诊为重症革兰阳性球菌感染的患者235例,随机将患者分为标准组(n=114)和指导组(n=121),通过高效液相色谱法(HPLC)开展血药浓度监测(TDM),获取反映药代动力学/药效学的参数,标准组按照说明书应用替考拉宁治疗,指导组在药代动力学指导下应用替考拉宁治疗,比较两组患者替考拉宁TDM、临床治疗疗效、病原菌清除情况、时间相关指标、血清炎症因子水平以及不良反应发生情况。结果采用HPLC法测定替考拉宁血药浓度线性范围为3.125~100μg/ml,线性回归方程为:Y=0.0465C-0.0132;指导组Cmin高于标准组,Cmin达标率优于标准组(P<0.05);指导组治疗总好转率为85.95%,高于标准组的67.54%(P<0.05);指导组病原菌总清除率90.91%,高于标准组的64.91%(P<0.05);指导组体温恢复时间、白细胞计数(WBC)恢复时间、血清C-反应蛋白(CRP)恢复时间及住院时间短于标准组(P<0.05);标准组、指导组患者治疗后血清WBC、CRP、肿瘤坏死因子-α(TNF-α)及降钙素原(PCT)水平较治疗前降低(P<0.05),治疗后指导组患者血清WBC、CRP、TNF-α及PCT水平低于标准组(P<0.05);指导组不良反应发生率2.48%,低于标准组的15.79%(P<0.05)。结论在药代动力学指导下应用替考拉宁治疗重症革兰阳性球菌感染患者,可根据药物浓度监测以制定个体化给药方案,从而保持较高的血药浓度,提高治疗效果,有效缓解患者临床症状,提高病原菌清除率,安全可靠。

OBJECTIVE To study the pharmacokinetic value of teicolanin in the treatment of severe gram-positive coccal infection. METHODS A total of 235 patients with severe Gram-positive cocci infection admitted in Zhengzhou Central Hospital Affiliated to Zhengzhou University from Jan. 2019 to Dec. 2019 were recruited, and the patients were randomly divided into the standard group(n=114) and guidance group(n=121). Therapeutic drug monitoring(TDM) was monitored by high-performance liquid chromatography(HPLC) to obtain the parameters reflecting pharmacokinetics/pharmacodynamics. The standard group was treated with teicoplanin according to the instructions, while the guidance group was treated under the guidance of pharmacokinetics. The TDM of teicoplanin, clinical treatment efficacy, pathogenic bacteria clearance, time-related indicators, serum inflammatory factors levels and occurrence of adverse reactions were compared between the two groups. RESULTS The linear range of teicoplanin concentration was 3.125~100 μg/ml by HPLC, and the linear regression equation was Y=0.0465 C-0.0132. The Cmin in the guidance group was significantly higher than that in the standard group, and the Cmin qualified rate was significantly higher than that in the standard group(P<0.05). The total improvement rate of treatment in the guidance group was 85.95%, which was significantly higher than that in the standard group of 67.54%(P<0.05). The total pathogenic bacteria clearance rate in the guidance group was 90.91%, which was significantly higher than that in the standard group(64.91%, P<0.05). The temperature recovery time, WBC recovery time, serum CRP recovery time and hospital stay in the guidance group were significantly shorter than those in the standard group(P<0.05). After treatment, the levels of serum WBC, CRP, TNF-α and PCT in the standard group and guidance group were significantly lower than those before treatment(P<0.05). After treatment, the levels of serum WBC, CRP, TNF-α and PCT in the guidance group were significantly lower than those in the standard group(P<0.05). The incidence rate of adverse reactions in the guidance group was 2.48%, which was significantly lower than that in standard group of 15.79%(P<0.05). CONCLUSION Teicoplanin administration under the guidance of pharmacokinetics in patients with severe Gram-positive cocci infection can be based on drug concentration monitoring to develop individualized drug administration program, so as to maintain a higher blood drug concentration, improve the therapeutic effect, effectively relieve the clinical symptoms of patients, and improve the clearance rate of pathogenic bacteria, and it is safe and reliable.