基于药学角度的假体周围感染常用抗菌药物关节腔内联合给药的可行性分析  

Combined intra-articular medication of commonly used antimicrobial agents for periprosthetic joint infection:an analysis of feasibility from a pharmaceutical perspective

作　　者：赵晓芳 张涛[2] 李梦秋 李欣宇[3] Zhao Xiaofang;Zhang Tao;Li Mengqiu;Li Xinyu(Department of Pharmacy,Qiandongnan Miao and Dong Autonomous Prefecture People's Hospital,Kaili 550000,China;Department of Orthopedics,the First Affiliated Hospital of Chongqing Medical University,Chongqing 400000,China;Department of Pharmacy,the First Affiliated Hospital of Chongqing Medical University,Chongqing 400000,China)

机构地区：[1]黔东南苗族侗族自治州人民医院药剂科,贵州凯里550000 [2]重庆医科大学附属第一医院骨科,重庆400000 [3]重庆医科大学附属第一医院药学部,重庆400000

出　　处：《实用药物与临床》2024年第8期571-577,共7页Practical Pharmacy and Clinical Remedies

摘　　要：目的从药学角度考察假体周围感染(Periprosthetic joint infection,PJI)常用关节腔抗菌药物联合方案的可行性,以期为其临床合理配伍提供依据。方法参考2020版《中国药典》标准,在室温下分别测定万古霉素(VAN)+美罗培南(MEM)、VAN+左氧氟沙星(LEV)、利奈唑胺(LZD)+MEM、LZD+LEV、LZD+哌拉西林他唑巴坦(PTZ)等配伍组合放置0 min、30 min、60 min、2 h、3 h、6 h后的澄清度、不溶性微粒数、pH值和渗透压,评估各组合的物理配伍稳定性。采用液质联用(HPLC-MS)技术检测上述配伍液中各药物的百分含量,评估各组合的化学稳定性。结果①VAN与MEM配伍后,物理和化学稳定性欠佳:澄清度(大量沉淀产生)、药物百分含量明显改变(VAN、MEM百分含量分别降低了12.23%、72.43%)。②VAN与LEV配伍后,物理稳定性欠佳,化学稳定性较好:不溶性微粒数超过《中国药典》相关标准,pH值低于人体耐受范围;③LZD与MEM配伍后,物理化学稳定性欠佳:澄清度明显改变(浅黄色),不溶性微粒数超过《中国药典》相关标准,药物百分含量明显改变(MEM百分含量降低了10.98%);④LZD与LEV配伍后,物理和化学稳定性欠佳:渗透压(<300 mOsm/L)低于健康关节液渗透压,LZD百分含量降低了11.63%;⑤LZD与PTZ配伍后,物理稳定性欠佳,化学稳定性较好:不溶性微粒数超过《中国药典》相关标准,渗透压(>600 mOsm/L)明显高于健康关节液。结论VAN+MEM、LZD+MEM 2种配伍组合不稳定,应避免联用;VAN+LEV、LZD+LEV、LZD+PTZ 3种配伍组合用于PJI的局部治疗可能是可行的,建议混合后采取过滤措施,并避免长期输注。Objective To investigate the feasibility of combined intra-articular medication of commonly used antimicrobial agents in periprosthetic joint infection(PJI)from a pharmaceutical perspective,and to provide a basis for rational clinical compatibility.Methods Referring to the 2020 edition of the“Chinese Pharmacopoeia”standards,the clarity,insoluble particle number,pH value and osmolality of vancomycin(VAN)+meropenem(MEM),VAN+le‐vofloxacin(LEV),linezolid(LZD)+MEM,LZD+LEV and LZD+piperacillin tazobactam(PTZ)were determined at room temperature to evaluate the physical stability of each drug combination after 0 min,30 min,60 min,2 h,3 h and 6 h of storage.The chemical stability of the drug combinations was evaluated by using High Performance Liquid Chromatography-Mass Spectrometry(HPLC-MS)technique to measure the percentage content of each drug in the above mixture.Results①The physical and chemical stability of VAN+MEM was poor:clarity(produced by a large amount of precipitation)and drug percentage content changed significantly(the percentage content of VAN and MEM was decreased by 12.23%and 72.43%,respectively).②The physical stability of VAN+LEV was poor,while the chemical stability was good:the number of insoluble particles exceeded the related standards of the“Chinese Pharma‐copoeia”,and the pH value was below the tolerance range of the human body.③The physical and chemical stability of LZD+MEM was poor:the clarity changed significantly(light yellow),the number of insoluble particles exceeded the related standards of the“Chinese Pharmacopoeia”,and the drug percentage content also changed significantly(MEM percentage content was reduced by 10.98%).④The physical and chemical stability of LZD+LEV was poor:the os‐motic pressure(<300 mOsm/L)was lower than that of healthy joint fluid,and the drug percentage of LZD was re‐duced by 11.63%.⑤The physical stability of LZD+PTZ was poor,while the chemical stability was good:the number of insoluble particles exceeded the related standards of the“Chi

关 键 词：假体周围感染 抗菌药物 合理用药 配伍稳定性 

分 类 号：R969[医药卫生—药理学]