多黏菌素E联合磷霉素对产碳青霉烯酶肺炎克雷伯菌的体外抗菌活性研究  

In Vitro Activity of Colistin Combination with Fosfomycin Against Klebsiella pneumoniae Carbapenemase-producing K. pneumonia

作　　者：贺吉童 陶静[3] 倪文涛[2] 王瑾[3] 王睿[3] 张勇[4] 

机构地区：[1]沈阳药科大学生命科学与生物制药学院,沈阳110032 [2]中国人民解放军总医院呼吸科,北京100853 [3]中国人民解放军总医院药物/器械临床试验中心,北京100853 [4]中国人民解放军总医院药材处,北京100853

出　　处：《中国药学杂志》2017年第13期1132-1136,共5页Chinese Pharmaceutical Journal

基　　金："十二五"国家重大科技专项基金资助项目(2012ZX09303004-002)

摘　　要：目的评价多黏菌素E联合磷霉素对74株产碳青霉烯酶肺炎克雷伯菌(Klebsiella pneumoniae carbapenemase-producing K.pneumoniae,KPC-Kp)的体外抗菌效应。方法分别用微量肉汤稀释法和琼脂平板稀释法测定多黏菌素E和磷霉素对74株KPC-Kp的最低抑菌浓度(MIC)值。用棋盘法计算部分抑菌浓度指数来判定联合效应。从中随机选取6株KPC-Kp测定多黏菌素E与磷霉素单用或联用的时间杀菌曲线。结果 MIC结果:多黏菌素敏感率100%,磷霉素敏感率为35.14%,FIC结果:多黏菌素E与磷霉素联合用药协同率为12.16%,部分协同率为39.19%,相加为6.76%,无关为41.89%,无拮抗作用。杀菌曲线结果:对于磷霉素敏感菌株,多黏菌素E联合磷霉素有明显的协同作用,磷霉素耐药菌株则没有明显协同作用。结论对于磷霉素敏感菌株,多黏菌素E与磷霉素联合用药在体外对KPC-Kp以协同作用和相加作用为主,杀菌曲线也显示了较好的协同作用,而磷霉素耐药菌株和多黏菌素协同作用较差。OBJECTIVE To evaluate the antibacterial effects of colistin combined with fosfomycin against KlebsieUa pneumoniae carbapenemase-producing K. pneumonia in vitro. METHODS The minimal inhibitory concentration（MIC） of colistin and fosfomycin against 74 strains of KPC-Kp was determined by agar dilution method and broth microdilution method respectively. The fractional inhibitory concentration index（ FICI ）was calculated by checkerboard method to determine the combined effect. SixKPC-Kp strains were randomly selected to determine the time-killing curves of colistin and fosfomycin alone or in combination. RESULTS The MIC results ： polymyxin sensitivity rate of 100%, fosfomycin sensitivity rate of 35.14%. The FIC results： In 74 strains,12. 16% synergism, 39. 19% section syn- ergism,6. 76% additive effect,41.89% irrelevant, no antagonism found. The results of time-kill assay showed that there was a significant synergistic effect between colistin and fosfomycin in fosfomycin-sensitive strains, while fosfomycin-resistant strains showed no synergistic effect. CONCLUSION In the case of fosfomycin-sensitive strains, the combination of colistin and fosfomycin has synergistic effects on KPC-Kp in vitro, and time-kill assay also shows a good synergistic effect. Resistant strains are poor in synergism.

关 键 词：多黏菌素E 磷霉素 联合用药 抗菌活性 肺炎克雷伯菌 

分 类 号：R965[医药卫生—药理学]