β-内酰胺类抗生素对阴沟肠杆菌高产AmpC酶突变的选择作用

Potential of Six β-Lactams to Select Mutants with Depressed AmpC β-Lactamase Synthesis from Enterobacter cloacae

目的 比较哌拉西林 /他唑巴坦、头孢哌酮 /舒巴坦、头孢他啶、头孢噻肟、头孢吡肟和亚胺培南对阴沟肠杆菌高产AmpC酶突变的选择能力。方法 以 10株单纯诱导产AmpC酶的阴沟肠杆菌和 5株诱导产AmpC酶并产超广谱β 内酰胺酶 (ESBLs)的阴沟肠杆菌为对象 ,采用肉汤稀释渐进突变选择法筛选突变株 ,三维试验监测受试菌的AmpC酶产生情况 ,琼脂稀释法测定突变株的抗生素敏感性。结果 在单纯诱导产AmpC酶的阴沟肠杆菌中 ,头孢他啶和头孢噻肟对高产AmpC酶突变的选择能力最强。在诱导产AmpC酶并产ESBLs的阴沟肠杆菌中 ,哌拉西林 /他唑巴坦对高产AmpC酶突变的选择能力最强。头孢吡肟对高产AmpC酶突变的选择作用较弱 ,但可逐渐增强部分受试菌对第三、四代头孢菌素的耐药性。亚胺培南对高产AmpC酶突变没有选择作用 ,也没有导致受试菌耐药性增强。结论 各种 β 内酰胺类抗生素对阴沟肠杆菌高产AmpC酶突变的选择能力是不一致的 ,在治疗由阴沟肠杆菌引起的各种感染时 ,应选择具有高抗菌活性、低选择能力的 β 内酰胺类抗生素。

OBJECTIVE To compare the potential of piperacillin/tazobactam, cefoperazone/sulbactam, cefotaxime, ceftazidime, cefepime and imipenem to select mutants with derepressed AmpC β-lactamase synthesis from Enterobacter cloacae. METHODS Ten non-ESBLs-producing strains and 5 ESBLs-producing strains of E. cloacae with inducible AmpC β-lactamase synthesis were employed. The strains were subcultured daily with the tested antibiotics at doubling concentrations starting at 0 25×MIC. Three-dimensional extract test was used to assess the expression of AmpC β-lactamase and standard agar dilution susceptibility tests were used to analyze the resistant phenotypes of mutants selected by antibiotics. RESULTS Ceftazidime and cefotaxime exhibited the highest potential to select derepressed mutants from non-ESBLs-producing strains. Piperacillin/tazobactam showed the highest potential to select derepressed mutants from ESBLs-producing strains. Cefepime showed low potential to select derepressed mutants. Imipenem failed to select resistance to itself or other tested β-lactam antibiotics. CONCLUSIONS Different β-lactams exhibited different potential in the selection of resistant mutants with derepressed AmpC synthesis from E. cloacae. The choice of antibiotic for therapy should be based not only on its antibacterial activity but also on its potential to select resistant mutants.