铜绿假单胞菌多黏菌素异质性耐药及联合药敏研究  

Colistin heteroresistance in Pseudomonas aeruginosa strains and their susceptibility to antibiotics used in combination

作　　者：许磊[1,2] 季京淑 张慧川[1] 史可人[1] 王海萍[1] 王燕飞[1] 俞云松[1] 

机构地区：[1]浙江大学医学院附属邵逸夫医院感染科,杭州310016 [2]宁波市医疗中心李惠利医院,315040

出　　处：《中华微生物学和免疫学杂志》2015年第12期869-874,共6页Chinese Journal of Microbiology and Immunology

基　　金：科技部973计划前期研究专项（2014CB560707）

摘　　要：目的明确多黏菌素（colistin）在多重耐药铜绿假单胞菌中的异质性及体外联合药敏情况。方法选择297株碳青霉烯类耐药铜绿假单胞菌，采用微量肉汤稀释法测定多黏菌素等抗菌药物的最低抑菌浓度（MIC）。采用群体谱分析方法分析多黏菌素敏感菌株的多黏菌素异质性，并分析部分菌株的杀菌曲线。采用棋盘法判断多黏菌素与亚胺培南、美罗培南、比阿培南、头孢他啶、左氧氟沙星、哌拉西林／他唑巴坦和头孢哌酮／舒巴坦的联合抑菌效应。结果药物敏感性试验提示99．66％的菌株对多黏菌素敏感。群体谱分析提示异质性耐药菌株比例为35％（7／20株），具有异质性的菌株比例为20％（4／20株）。联合药敏提示多黏菌素联合用药对异质性耐药菌株的作用以协同和相加为主，而对无异质性的菌株则主要表现为相加和无关作用。结论多重耐药铜绿假单胞菌对多黏菌素的敏感性很高，但异质性及异质性耐药现象较为普遍。多黏菌素与其他多种抗菌药物联合对异质性耐药菌株的作用增强。Objective To analyze the colistin heteroresistance in Pseudomonas aeruginosa strains and their in vitro susceptibility to antibiotics used in combination. Methods Two hundred and ninety-seven carbapenem-resistant Pseudomonas aeruginosa strains were selected for this study. Broth microdilution method was used to determine the minimum inhibitory concentrations of colistin and other antimicrobials against the Pseudomonas aeruginosa strains. The colistin heterogeneity of 20 colistin sensitive strains was analyzed by using population analysis profiles. The time-kill curves of 3 randomly selected colistin heteroresistant strains were used to determine the bacteriostatic activity of colistin. Chequer-board method was used to measure the combination efficacy of eolistin with other antimicrobials including imipenem, meropenem, biapenem, ceftazidime, levofloxcin, piperacillin/tazobactam and cefoperazone/sulbactam. Results The colistin sensitive Pseudomonas aeruginosa strains accounted for 99.66% of the 297 isolates. Population analysis profiles displayed that 35% of the 20 isolates were colistin heteroresistant and 20% of the 20 isolates were heterogeneous. It showed that when colistin was used in combination with other drugs, they mainly had synergistic and additive effects on heteroresistant isolates, but additive and indifferent effects on non-heterogeneous isolates. Conclusion Multidrug resistant Pseudomonas aeruginosa strains were highly susceptible to colistin, but heteroresistant and heterogeneous strains were common. The efficacy of colistin against heteroresistant isolates could be enhanced by using in combination with other drugs.

关 键 词：多重耐药 铜绿假单胞菌 多黏菌素 异质性耐药 异质性 

分 类 号：R446.5[医药卫生—诊断学]