妥布霉素和亚胺培南联合用药对铜绿假单胞菌有协同抑制效应  

Tobramycin combined with Imipenem had synergistic inhibitory effect on Pseudomonas aeruginosa

作　　者：曹静 向雅婷 孙玥 王帆 吴红肖 戴璐 韩怡婷 褚少朋[1] 俞娟[1,2] CAO Jing;XIANG Yating;SUN Yue;WANG Fan;WU Hongxiao;DAI Lu;HAN Yiting;CHU Shaopeng;YU Juan(Department of Laboratory Medicine,the Affiliated Hospital of Nantong University,Nantong 226001;Department of Medical Laboratory,Institute of Public Health,Nantong University)

机构地区：[1]南通大学附属医院医学检验科,南通226001 [2]南通大学公共卫生学院医学检验系

出　　处：《南通大学学报（医学版）》2021年第2期126-130,共5页Journal of Nantong University(Medical sciences)

基　　金：南通市基础科学研究项目(JC2018067);南通大学大学生创新训练计划项目(2019155)。

摘　　要：目的:收集南通大学附属医院分离的临床多重耐药铜绿假单胞菌,使用临床常用抗菌药物在体外联合作用于多重耐药铜绿假单胞菌,筛选出有协同作用和累加作用的组合并评价该组合的体外抗菌效果。方法:使用世界卫生组织推荐的细菌耐药监测专用软件WHONET5.5进行数据分析,采用K-B法初筛联合用药组合效果。采用棋盘稀释法测定不同浓度组合的抗菌药物组合对103株临床多重耐药铜绿假单胞菌的最低抑菌浓度(minimum inhibitory concentration,MIC)值,并计算联合用药的部分抑菌浓度指数(fractional inhibitory concentration index,FICI)来判断药物联合效应。最后检测筛选出的妥布霉素和亚胺培南单独和联合应用时的杀菌曲线。结果:K-B法筛选出具有协同作用和累加作用的药物组合有:妥布霉素与亚胺培南、哌拉西林/他唑巴坦与阿奇霉素、头孢他啶与亚胺培南、哌拉西林/他唑巴坦与亚胺培南、哌拉西林/他唑巴坦与头孢他啶、头孢他啶与阿奇霉素、亚胺培南与阿奇霉素。选择妥布霉素和亚胺培南进行联合药敏试验,棋盘稀释法检测结果为妥布霉素与亚胺培南对铜绿假单胞菌联合用药表现协同作用为16.5%,累加作用为35.9%,无关作用为47.6%,拮抗作用为0;进一步的杀菌曲线检测结果显示妥布霉素和亚胺培南协同作用明显。结论:临床痰液中分离的铜绿假单胞菌耐药尤为严重,此次实验从临床常用抗菌药物中成功筛选出妥布霉素和亚胺培南药物组合,并发现两者联合用药比单独用药效果好,为临床治疗多重耐药铜绿假单胞菌感染增加了一种用药选择。Objective:Clinical multi-drug resistant Pseudomonas aeruginosa isolated from Affiliated Hospital of Nantong University was collected and combined with common clinical antibacterial drugs on clinical multi-drug resistant Pseudomonas aeruginosa in vitro.The combination with synergistic effect and cumulative effect were screened out and its antibacterial effect in vitro was evaluated.Methods:Data were analyed with WHONET5.5 recommended by the World Health Organization Center for bacterial tolerance monitoring.Using K-B method to detect the effect of combined use of drugs.Used checkerboard method for determining the antimicrobial drug combinations of different concentration combinations of 103 strains of clinical multi-drug resistant Pseudomonas aeruginosa minimum bacteriostatic concentration minimum inhibitory concentration(MIC),the fractional inhibitory concentration index(FICI)of the drug combination was calculated to determine the effect of the drug combination.Finally,the bactericidal curves of Tobramycin and Imipenem were detected when they were used separately and in combination.Results:The combination of drugs with synergistic effect and cumulative effect were selected by K-B method as follows:Tobramycin and Imipenem,Piperacillin/Tazobactam and Azithromycin,Ceftazobactam and Imipenem,Piperacillin/Tazobactam and Imipenem,Piperacillin/Tazobactam and Ceftazidime,Ceftazidime and Azithromycin,Imipenem and Azithromycin.In the experiment,Tobramycin and Imipenem were selected for further combined drug sensitivity test.The results of checkerboard method showed that the synergistic effect of Tobramycin and Imipenem on Pseudomonas aeruginosa was 16.5%,the additive effect was 35.9%,the irrelevant effect was 47.6%,and the antagonistic effect was 0.The results of bactericidal curve showed that Tobramycin and Imipenem had obvious synergistic effect.Conclusion:Pseudomonas aeruginosa resistance isolated from clinical sputum was particularly severe.In this experiment,the combination of Tobramycin and Imipenem was successfully

关 键 词：铜绿假单胞菌 耐药 联合用药 协同作用 妥布霉素 亚胺培南 

分 类 号：R378.991[医药卫生—病原生物学]