摘要目的 探讨成人患者万古霉素血药浓度与临床疗效、不良反应之间的关系,为临床优化给药提供指导.方法 采用前瞻性观察性临床研究.选择2013年7月1日至2017年12月31日上海交通大学附属第一人民医院收治的革兰阳性(G+)菌感染并使用万古霉素治疗的成人患者.根据肌酐清除率决定给药剂量,并结合监测的万古霉素血药浓度和患者的治疗反应调整万古霉素给药方案,同时记录给药前后患者的临床相关资料,如病原菌清除情况、血常规、肝肾功能、不良反应等,分析万古霉素治疗G+菌感染的有效性及安全性.结果 共收集89例符合入选标准的病例,男性占67.42% ;年龄(50.5±17.9)岁;以血流感染为主(占61.80%),其次为下呼吸道感染(占17.98%);金黄色葡萄球菌引起的感染占39.33% ;细菌清除率为89.89% (80/89);综合治疗有效率为77.53%(69/89).致病菌最低抑菌浓度(MIC)＜2 mg/L者的治疗有效率为80.30% (53/66),MIC≥2 mg/L者为69.57%(16/23),二者差异无统计学意义(χ2＝1.129,P＝0.288).万古霉素谷浓度＜10 mg/L者的治疗有效率为72.92%(35/48),谷浓度≥10 mg/L者为82.93%(34/41),二者差异也无统计学意义(χ2＝1.272,P＝0.259).89例患者中有4例治疗后出现万古霉素相关肾毒性损伤,肾毒性损伤发生率为4.49%,该4例患者万古霉素谷浓度为17.22～28.53 mg/L ;33例发生肝功能异常,其中以γ-谷氨酰转移酶、碱性磷酸酶和天冬氨酸转氨酶升高为主;2例治疗过程中出现白细胞减少;2例出现皮疹.结论 万古霉素血药谷浓度、致病菌MIC可能与G+菌感染患者的治疗效果没有相关性;但是当万古霉素谷浓度超过15 mg/L时肾毒性损伤发生率明显升高.临床试验注册 中国临床试验注册中心,ChiCTR-OPC-16007920.

abstractsObjective To investigate the relationship between the serum level of vancomycin and its clinical efficacy as well as adverse reactions in adult patient so as to provide recommendations for clinical management. Methods An open observational research was performed from 1st July 2013 to 31st December 2017 in Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, which recruited the adult patients who were infected with Gram positive (G+) bacteria and treated with vancomycin. The initial dose was decided by the patient's creatinine clearance rate, and the treating dose was directed by the serum drug concentration and the patient's clinical response. By recording the associated clinical information (pathogen eradication, blood test results, adverse reactions, etc.), the clinical outcome and adverse reactions for vancomycin to treat G+bacterial infections were analyzed. Results Eighty-nine cases who meet research standards were finally recruited, with 67.42% of male patients, and an average age of (50.5±17.9) years. The most common type of infection was bloodstream infection (61.80%), followed by low respiratory infection (17.98%). Infections caused by Staphylococcus aureus accounted for 39.33%. The bacterial eradication rate was 89.89% (80/89) and the total effective rate was 77.53% (69/89). The effective rate was 80.30% (53/66) with minimum inhibitory concentration (MIC) < 2 mg/L vs. 69.57% (16/23) with MIC ≥ 2 mg/L, the difference was not statistically significant (χ2= 1.129, P = 0.288). The effective rate was 72.92% (35/48) with trough levels <10 mg/L vs. 82.93% (34/41) with trough levels ≥ 10 mg/L, the difference was not statistically significant (χ2= 1.272, P = 0.259). There were 4 cases of vancomycin associated nephrotoxicity, the incidence of nephrotoxicity was 4.49%, and the vancomycin serum trough levels were 17.22-28.53 mg/L. There were 33 cases of liver dysfunction, and elevated γ-glutamine transferase, alkaline phosphatase and aspartate aminotransferase were most common. There were 2 cases of neutropenia and 2 patients appeared rash during vancomycin period. Conclusions Treatment outcomes were similar regardless of vancomycin MIC and serum trough level. The incidence of vancomycin associated nephrotoxicity rises apparently when serum trough level is over 15 mg/L. Clinical Trial Registry Chinese Clinical Trail Registry, ChiCTR-OPC-16007920.