米卡芬净联合头孢他啶对铜绿假单胞菌生物被膜形成与清除的研究  

Effect of micafungin combined with ceftazidime on clearance of the biofilms formed by Pseudomonas aeruginosa

作　　者：李艳华 张树逍 杨阳 徐广健 邓启文[2] LI Yanhua;ZHANG Shuxiao;YANG Yang;XU Guangjian;DENG Qiwen(Department of Laboratory Medicine,Huazhong University of Science and Technology Union Shenzhen Hospital,Shenzhen Guangdong 518052,China)

机构地区：[1]华中科技大学协和深圳医院检验科,广东深圳518052 [2]华中科技大学协和深圳医院感染科,广东深圳518052

出　　处：《中国感染与化疗杂志》2022年第4期441-447,共7页Chinese Journal of Infection and Chemotherapy

基　　金：深圳市南山区科技计划项目(2019024)。

摘　　要：目的分析米卡芬净联合头孢他啶对铜绿假单胞菌生物被膜的抑制和清除作用。方法筛选成膜能力强的4株铜绿假单胞菌临床株,使用肉汤微量稀释法测定米卡芬净、头孢他啶对铜绿假单胞菌浮游相和被膜相的MIC。采用微孔板构建体外被膜模型,设立米卡芬净组、头孢他啶组、米卡芬净联合头孢他啶组和无药对照组。采用结晶紫染色法,观察米卡芬净单用和联用抑制被膜形成及清除成熟被膜的效果。根据方差齐性采用Student-t检验或近似t检验,使用SPSS 23.0软件进行统计分析,以P<0.05为差异有统计学意义。结果未测得米卡芬净对铜绿假单胞菌的MIC;加入米卡芬净后,头孢他啶对铜绿假单胞菌浮游相MIC无任何变化,但对被膜相(3/4株)MIC降低50%。米卡芬净对所有菌株被膜形成均表现出良好的抑制效果,对成熟被膜也具有较好的清除作用。亚抑菌浓度的头孢他啶对铜绿假单胞菌被膜形成有明显的抑制作用,高浓度头孢他啶对成熟被膜有明显的清除作用,但与米卡芬净联用表现出拮抗作用,对所有被膜的形成和其中3株成熟被膜的清除效果均低于米卡芬净单用。结论米卡芬净单用对铜绿假单胞菌生物被膜的形成和清除均有明显的效果,但与头孢他啶联合表现出拮抗作用。Objective To analyze the effect of micafungin combined with ceftazidime on the biofilms produced by Pseudomonas aeruginosa.Methods Four clinical isolates of P.aeruginosa capable of biofilm formation were collected.The minimum inhibitory concentrations(MICs)of micafungin and ceftazidime were determined by broth microdilution method against the planktonic phase and biofilm-forming phase strains.In vitro biofilm model was constructed using microwell plate.The strains were tested by different treatments,including micafungin intervention,ceftazidime intervention,micafungin plus ceftazidime,and control group.Crystal violet staining was used to observe the effect of micafungin alone and in combination on inhibiting biofilm formation and removing the mature film.SPSS 23.0 statistical software was used for data analysis.Student t-test or approximate t-test was used based on homogeneity of variance in comparing the difference between treatment groups.P<0.05 indicates significant difference.Results MIC of micafungin was not detected.Micafungin combined with ceftazidime did not reduce the MIC of ceftazidime against the planktonic bacterial strains,but slightly reduced the MIC against 3 of the 4 biofilm-forming phase strains.Micafungin showed good inhibitory effect on biofilm formation of all strains,and capacity of eradicating the mature biofilm.Sub-MIC ceftazidime apparently inhibited biofilm formation and high concentration ceftazidime apparently eradicated the mature biofilm,but ceftazidime combined with micafungin had an antagonistic effect on eradicating biofilm,evidenced by lower effect on biofilm formation of all strains and lower effect on eradicating the mature biofilm of 3 strains.Conclusions Micafungin has an obvious effect on the biofilm formation of P.aeruginosa and eradicating the mature film,but the effect is reduced when combined with ceftazidime.

关 键 词：铜绿假单胞菌 生物膜 米卡芬净 头孢他啶 拮抗作用 

分 类 号：R978[医药卫生—药品] R378.991[医药卫生—药学]