Objective To study the mechanisms on drug susceptibility and resistance of clinically multidrug-resistant Escherichia coli isolates,to provide information on related treatment.Methods The susceptibility of E.coli strains that isolated from different kinds of samples in the last 3 years on drugs was analyzed by agar dilution test,with strains that exhibiting resistances to cefotuxime,ciprofloxacin and amikacin simultaneously collected for further analysis.Resistant genes which mediate resistance to β-lactamases,fluoroquinolone and aminoglycoside as well as phylogenic type were detected by PCR amplification while genetic relation was analyzed by PFGE.Transferability of resistant plasmids was identified by conjugation test.Results In total,137 multidrug-resistant E.coli isolates were collected.Only 1％ of the isolates exhibited resistance to both imipenem and meropenem while 4％ of the strains were resistant to piperacillin/tazobactam.Most (85％) of the isolates were positive to ESBL and majority of them produced CTX-M.Target substitution and production of methylases were the main mechanisms causing resistance to fluoroquinolones and aminoglycosides respectively.Conclusion The main source of clinical multidrug-resistance was collected from urine samples.Carbapenem and enzyme inhibitor-containing antibiotics seemed to be the available antibiotics that were sentitive to the clinically multidrug-resistant E.coli isolates.%目的 探讨临床分离的多耐药大肠埃希菌对常用抗生素的敏感性及其耐药机制.方法 采用琼脂稀释法对北京市城区3家三甲医院近3年从各种临床标本分离的大肠埃希菌进行药敏试验,收集对头孢噻肟、环丙沙星和阿米卡星同时耐药的多耐药菌株；采用PCR和测序方法检测上述多耐药菌株对β-内酰胺类、喹诺酮类和氨基糖苷类的耐药基因,并对菌株进行系统发生分型；使用脉冲场凝胶电泳(PFGE)分析菌株同源性；通过接合试验观察耐药质粒的传递性.结果 共检出137株多耐药大肠埃希菌.其中分离自尿液的比例最高(41.61％)；除对亚胺培南和美罗培南耐药率(均为1％)较低外,对哌拉西林、他唑巴坦的耐药率也较低(4％)；85％的多耐药大肠埃希菌产超广谱β-内酰胺酶(ESBL),且多为CTX-M型；介导菌株对喹诺酮类药物耐药的主要原因是药物靶位突变；导致菌株对阿米卡星耐药的机制主要是产生16S rRNA甲基化酶(ArmA或RmtB).结论 临床分离多耐药大肠埃希菌主要来自尿液标本；除碳青霉烯类,酶抑制剂抗生素可能也是治疗该类菌株引起感染的有效药物.
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