头孢曲松-舒巴坦复方制剂对产ESBLs大肠埃希菌持续效应的研究

Persistent effects of ceftriaxone-sulbactam combination on extended-spectrum β-lactamases-producing E. coli

目的测定头孢曲松-舒巴坦复方制剂(2∶1)对产ESBLs大肠埃希菌的MIC和持续效应。后者包括抗生素后效应(PAE)、内酰胺酶抑制剂后效应(PLIE)和亚抑菌浓度后效应(PASME)。方法以肉汤试管稀释法测定MIC。将大肠埃希菌与一定冲击浓度的头孢曲松-舒巴坦作用2h后,在不同药物浓度条件下继续培养,用倾皿培养法进行菌落计数(CFU/mL),以log(CFU/mL)对培养时间(h)绘制生长曲线,计算PAE、PLIE和PASME。结果①头孢曲松和头孢曲松-舒巴坦对大肠埃希菌的MIC分别为8/4mg/L和大于256mg/L。②头孢曲松和头孢曲松-舒巴坦对大肠埃希菌的PAE为负值或很短。③舒巴坦对大肠埃希菌的PLIE在低冲击浓度(2MIC、4MIC)时为负值或很短,当浓度增加至10MIC时,其PLIE>6.5h。结论时间依赖的头孢曲松-舒巴坦对产ESBLs大肠埃希菌的PLIE存在明显的浓度依赖效应,为了提高头孢曲松-舒巴坦的临床疗效,其给药方法的设计除了要延长T>MIC外,适当提高给药的峰浓度或许亦有利于疗效的发挥。

Objective To measure the minimal inhibitory concentration （MIC） and persistent effects of ceftriaxone-sulbactam combination （2 ： 1） on extended-spectrum β-lactamase-producing E. coli. The persistent effects include post-antibiotic effect （PAE）, post-β-lactamase inhibitor effect （PLIE） and post antibiotic sub-MIC effect （PASME）. Methods The MIC were determined by broth microdilution method. E. coli strains were exposed to certain concentration of ceftriaxone-sulbactam for 2 hours. The E. coli strains were cultured with various concentrations of antibiotic. The number of colony forming units （CFU） in incubated broth was counted by plating method. The PAE, PLIE and PASME of eeftriaxone-sulbactam on E. coli were calculated according to the logCFU/mL-time （h） curve. Results The MIC of ceftriaxone and eeftriaxone-sulbactam were 〉256 mg/L and 8/4 mg/L respectively. The PAE of ceftriaxone and ceftriaxone-sulbactam against extended-spectrum β-lactamase-producing E. coli were short or negative. PLIE induced by sulbactam on extended-spectrum β-lactamase-producing E. coli were short or negative at low exposure concentrations of ceftriaxone-sulbactam （2 × MIC, 4 × MIC） and exceeded 6.5 h at 10 x MIC. Conclusions The time-dependent ceftriax- one-sulbactam has significant effect on the PLIE of sulbactam against extended-spectrum β-lactamase-producing E. coli, which is concentration-dependent. In addition to increasing the time over MIC, increasing the peak concentration of ceftriaxone-sulbactam may also be beneficial for clinical out-comes of ceftriaxone sulbactam combination therapy.