载万古霉素和美罗培南骨水泥人体局部释放研究

目的: 研究万古霉素联合美罗培南骨水泥用于骨感染患者治疗的局部释放特点及规律。方法: 2020年6月至2021年3月北京积水潭医院创伤骨科收治的骨感染患者,手术感染病灶中植入万古霉素联合美罗培南骨水泥链珠,局部留置引流管,分别于术后2 h及每日清晨留取伤口引流液标本及静脉血,使用酶放大免疫法和超高效液相色谱-串联质谱法测定万古霉素和美罗培南浓度。结果: 共纳入21例骨感染患者,局部释放率两药最高峰均出现在10 h,最大释放速率万古霉素和美罗培南分别为4.761,1.149 mg·h^-1,累计局部释放率分别为6.38%,1.41%;术后2 h引流液中万古霉素和美罗培南药物质量浓度分别为(373.06±357.70) mg·L^-1,(158.41±121.33) mg·L^-1;血药浓度最大值分别为1.1,0.54 mg·L^-1。结论: 万古霉素联合美罗培南骨水泥自制链珠局部植入骨感染病灶可以在术后短期内获得高组织浓度,万古霉素局部药物浓度更高,两药全身药物浓度均很低安全性高。

Local release of vancomycin and meropenem from antibiotic-loaded bone cement in human

OBJECTIVE To study the local release characteristics of vancomycin combined with meropenem bone cement in patients with bone infection.METHODS Patients with bone infection who were treated in the department of orthopedics and trauma of Beijing Jishuitan Hospital from June 2020 to March 2021 were collected.The vancomycin and meropenem bone cement beads were implanted into the infection lesions,and the localized drainage tube was implanted.The wound drainage fluid samples and venous blood were collected 2 h after operation and every morning until the drainage tube was removed.The concentration of vancomycin and meropenem in drainage fluid and plasma were determined by Enzyme amplification immunoassay and ultra performance liquid chromatography-tandem mass spectrometry.RESULTS Twenty one patients participated in the study.The peak of local release rate of both drugs occurred in 10 hours.The maximum release rate of vancomycin and meropenem were 4.761,1.149 mg·L^-1.The cumulative local release rate were 6.38% and 1.41%.The concentration of drainage fluid were (373.06±357.70) mg·L^-1,(158.41±121.33) mg·L^-1within 2 hours after operation.The maximum plasma concentrations were 1.1,0.54 mg·L^-1.CONCLUSION Local implantation of vancomycin combined with meropenem bone cement self-made chain into bone infection lesions can obtain high tissue concentration in short period after operation.The local drug concentration of vancomycin is higher and the maintenance time is longer than meropenem.The systemic drug concentration of both drugs is very low,and it is a safe method.