头孢曲松/他唑巴坦对产β-内酰胺酶大肠埃希菌后效应的研究

Post Antibiotic,Post β-lactamase Inhibitor and Post Antibiotic Sub-MIC Effect of Ceftriaxone/Tazobactam on β-lactamase-producing Escherichia coli in vitro

目的探讨头孢曲松/他唑巴坦复方(CRO/TAZ)对产β-内酰胺酶大肠埃希菌的体外抗菌活性(MIC)、抗生素后效应(PAE)、β-内酰胺酶抑制剂后效应(PLIE)和抗生素亚抑菌浓度后效应(PASME)。方法采用琼脂二倍稀释法测定CRO/TAZ和CRO对产4种酶型β-内酰胺酶E.coli菌株的MIC;以微量接种菌落计数法测定菌落形成单位(CFU),绘制细菌生长曲线,并计算PAE、PLIE和PASME。结果CRO/TAZ复方对产β-内酰胺酶菌株的MIC较CRO单方降低都在8倍以上;无论CRO单方还是CRO/TAZ复方均无长的PAE(-0.59～0.85 h);PLIE和PASME随着菌株β-内酰胺酶酶型的不同而不同,相同酶型的菌株PLIE和PASME很接近;PLIE(0.62～3.22 h)和大多数PASME(0.12～5.61 h)都较其PAE长,而且对CRO单方MIC较小的菌株,其PAE、PLIE和PASME较长。结论PLIE和PASME的长短可能与β-内酰胺酶酶型有关。对于有较长PLIE和PASME的菌株,在制定临床给药方案时可适当延长给药间隔;PAE、PLIE和PASME理论为研究抗菌药物药效学和设计合理给药方案、优化给药模式提供重要参考和新思路。

Objective To study post antibiotic effect（PAE）,post β-lactamase inhibitor effect（PLIE） and post antibiotic sub-MIC effect（PASME） of ceftriaxone/tazobactam on β-lactamase-producing Escherichia coli in vitro.Methods The minimal inhibitory concentration（MIC） of ceftriaxone/tazobactam against 4 types of β-lactamase producing E.colis strains,was measured by two-fold agar dilution method.The numbers of CFU on plates were counted by micro-inoculation colony counting method.The growth kinetics curves of the bacteria were drawn according to CFU counts,from which the PAE,PLIE and PASME were calculated.Results The MIC of the ceftriaxone/tazobactam combination was eight times more than ceftriaxone alone.No longer PAE（-0.59-0.85 h） was found in the ceftriaxone/tazobactam combination or any of them alone.The PLIE and PASME varied according to the type of β-lactamase but similar results were observed for the strains producing the same type β-lactamase.All PLIEs（0.62-3.22 h） and most PASMEs（0.12-5.61 h） were longer than PAEs.The lower MIC of ceftriaxone the strain had,the longer the PAE,PLIE and PAMSE were.Conclusion The duration of PLIE and PASME may concerned with the type of β-lactamase.With both longer PLIE and PASME,longer dosing interval should be recommended.The PAE,PLIE and PASME provide an important instrument for pharmacodynamic studies of antibiotics,in particular for the design of dosing schedules.