依替米星联合美罗培南、哌拉西林他唑巴坦对多重耐药铜绿假单胞菌突变选择窗的研究  

Mutant selection window of etimicin combined with meropenem or piperacillin tazobactam against multi-drug resistant Pseudomonas aeruginosa

作　　者：毕玲玲[1] 孙成春[2] 公衍文[3] 张欣悦[1] 

机构地区：[1]辽宁医学院研究生院,辽宁锦州121001 [2]济南军区总医院药剂科,山东济南250031 [3]济南军区总医院实验诊断科,山东济南250031

出　　处：《中国医院药学杂志》2015年第7期597-601,共5页Chinese Journal of Hospital Pharmacy

摘　　要：目的：探讨依替米星（ETM）与美罗培南（MEM）、哌拉西林他唑巴坦（TZP）体外联合对多重耐药铜绿假单胞菌（MDRP）耐药突变选择窗的影响,为降低细菌耐药的产生提供依据。方法：分别采用棋盘法、琼脂平板稀释法测定24株临床分离MDRP的最低抑菌浓度（MIC）和防耐药突变浓度（MPC）,并计算相应的部分抑菌浓度（FIC）指数及选择指数（SI）。结果：ETM联用MEM、TZP后,对标准菌株的MIC、MPC、SI值较单用时明显降低,并表现为协同作用。ETM＋MEM与ETM＋TZP对24株MDRP有协同抗菌作用的分别占37.50%、33.33%,相加作用分别占58.33%、41.67%,无关作用分别占4.17%、25.00%,均无拮抗作用。ETM、MEM、TZP单用对24株MDRP的SI分别为8~32、8~32、8~32,ETM分别与MEM、TZP联合后各自单药的SI分别为ETM＋MEM（ETM-1~8,MEM-1~8）、ETM＋TZP（ETM-1~8,TZP-1~16）。结论：ETM与MEM、TZP联合后,可降低各药对铜绿假单胞菌的MPC值,缩小MSW,有利于防止细菌耐药突变体的产生。OBJECTIVE To study the changes of mutant selection window（MSW）in multi-drug resistant Pseudomonas aeruginosa（MDRP）used etimicin（ETM）combined with meropenem（MEM）or piperacillin tazobactam（TZP）,and provide the laboratory evidence for preventing bacterial resistance.METHODS The minimum inhibitory concentration（MIC）of 24 clinical isolates of MDRP used ETM combined with MEM or TZP were determined by checkerboard microdilution assay to calculate the fractional inhibitory concentration（FIC）index.In addition,the mutant prevention concentration（MPC）of 24 clinical isolates of MDRP used ETM combined with MEM or TZP were determined by agar plate dilution assay to calculate the selection index（SI）.RESULTS When ETM combined with MEM or TZP,the MIC,MPC and SI reduced evidently compared with the single treatment.And there was synergistic effects against standard strains when treated with ETM＋MEM or ETM＋TZP.The synergic antibacterial effects against MDRP strains were 37.50% and 33.33%,additive effects were 58.33% and41.67%,and unrelated effects were 4.17% and 25.00% respectively,with no antagonistic effects when ETM combined with MEM or TZP.The SI of the 24 isolates treated with ETM,MEM or TZP alone was 8-32,8-32 and 8-32,respectively.Compared with the single treatment,the SI of ETM reduced to 1-8 when ETM combined with MEM or TZP,and the SI of MEM or TZP reduced to 1-8 and 1-16.CONCLUSION These results suggest that the combination treatment of ETM＋MEM and ETM＋TZP against pseudomonas aeruginosa might lower the MPC of the isolates treated with ETM/MEM/TZP alone,narrow the mutant selection window,and prevent the generation of drug-resistant mutants,

关 键 词：依替米星 美罗培南 哌拉西林他唑巴坦 突变选择窗 

分 类 号：R978.1[医药卫生—药品]