产ESBLs及AmpC大肠埃希菌耐药性分析

Drug Resistance Analysis of ESBLs and AmpC Beta-lactamases in Clinical Isolates of Escherichia Coli

目的 调查对头孢菌素耐药的大肠埃希菌的耐药机制及对15种抗生素的耐药性与耐药特点。方法 对华中科技大学同济医学院附属同济医院检验科2004年1～12月临床分离的468株大肠埃希菌采用琼脂二倍稀释法测定15种抗生素的最低抑菌浓度（MIC），标准纸片扩散法检测超广谱G-内酰胺酶（ESBLs），改良三维试验检测头孢菌素酶（AmpC）。结果 468株大肠埃希菌中检出ESBLs153株，检出率32．7％（153／468），AmpC酶7株，检出率1．5％（7／468）。产ESBLs大肠埃希菌对二代头孢耐药率大于90％，对三代头孢耐药率为30．4％（头孢他啶）和55．4％（头孢噻肟），对四代头孢（头孢吡肟）耐药率为58．9％，对酶抑制剂联合制剂阿莫西林／克拉维酸和头孢哌酮／舒巴坦的耐药率为92．9％和80．4％，对环丙沙星的耐药率为83％，对庆大霉素的耐药率为73．3％，对四环素的耐药率为88％。产AmpC酶大肠埃希菌表现出更高的耐药性，对二、三代头孢、四环素、环丙沙星和庆大霉素100％耐药，对四代头孢（头孢吡肟）的耐药率达71．4％，对酶抑制剂联合制剂阿莫西林／克拉维酸和头孢哌酮／舒巴坦的耐药率为100％和71．4％，对单环酰胺类的氨曲南耐药率为85．7％。非产ESBLs和AmpC大肠埃希菌的耐药率明显低于产酶者，碳青霉烯类的亚胺培南对所有测试菌株的耐药率为0，MIC50为0．5mg／L。结论 （1）对头孢菌素耐药的大肠埃希菌的耐药机制主要是产生ESBLs。（2）产AmpC酶大肠埃希菌比ESBLs耐药更严重，仅亚胺培南对其有效。（3）在临床抗感染治疗中应依据药物敏感试验合理选择抗生素，尽量少选具有诱导细菌产酶的抗生素。

Objective To study the mechanisms of drug resistance in clinical isolates of Escherichia coli against 15 anti- bacterial agents. Methods A total of 468 strains of Escherichia coli isolated from January 2004 to December 2004 were collected from Tongji Hospital Affiliated to Tongji Medical College, Huazhong University of Science and Technology. The MIC of 15 antibacterial agents against the clinical isolates was detected by the double agar dilution method. ESBLs and AmpC- producing E. coli isolates were examined by standard disk diffusion susceptibility test and improved new three - dimensional test. Results Altogether 153 ESBLs - producing strains were detected in the 468 Escherichia coli isolates, and the detection rate was 32. ？% （153/468）. Additional / AmpC - producing strains were detected and the detection rate was 1.5% （7/ 468）. Resistant rates of second- generation cephlosporin in ESBLs - producing were mere than 90% i In the third - generation cephlosporin, the resistant rates to cefatazidime and cefotaxime were 30.4% and 55.4%, respectively. In the forth- generation cephlosporin, the resistant rate to cefepime was 58.9%. Among the beta- lactamase inhibitor combination regimens, the resistant rates to amoxicillin/clavulanate and cefoperazone/sulbactarn were 92.9% and 80.4%, respectively. The resistant rate to ciprofloxacin was 83%. For gentamicin and tetracycline,the rates of resistance were 73.3% and 88%, re- spectively. The AmpC - producing strains revealed a higher drug resistance comparing with ESBLs- producers. The AmpC - producers were all resistant to the second and third - generation cephlosporins, tetracycline, ciprofloxacin and gentarnicin. The resistant rates of non- ESBLs and non - AmpC - producers were less than that of the beta- lactamase producers. For imipenem, no resistant strain was found in all these E. coli strains, which showed a significant antibiotic activity and the MIC50 was only 0. 5 microgram per liter. Conclusions The mechanisms of cephlosporin- resistant in Escherichia coli were mainly producing ESBLs. AmpC - producing strains in Escherichia coli revealed a critical drug resistance. Imipenem is the most active antibiotic for treatment of the infections caused by these resistant strains. The choices of antibiotics for clinical therapy must be recommended to the results of susceptibility test in vitro.