头孢噻肟及他唑巴坦对β-内酰胺酶稳定性的初步研究

Study on enzyme stability of cefotaxime/tazobactam to β-lactamases

目的:测定头孢噻肟钠他唑巴坦钠(1∶1,2∶1,4∶1,8∶1,16∶1)及单组分头孢噻肟钠(CTX)对13种产酶株β-内酰胺酶粗提液的水解率及抑酶保护率,并与复方制剂头孢哌酮钠舒巴坦钠和哌拉西林钠他唑巴坦钠进行比较。方法生物法测定β-内酰胺酶对抗生素的相对水解率以及抑酶保护率。结果不同配比头孢噻肟钠他唑巴坦钠的相对水解率均显著低于头孢噻肟钠单用(P<0.01);与头孢哌酮钠舒巴坦钠(CPZ/SB 1∶1)和哌拉西林钠他唑巴坦钠(PIPC/TB 8∶1)的相对水解率相比,CTX/TB(1∶1)的相对水解率有明显降低(P<0.05),且显著低于CTX/TB(8∶1,16∶1)(P<0.05),也低于CTX/TB(2∶1,4∶1)但无统计学意义。结论CTX/TB(1∶1)抑酶效应优于其他配比,且优于同类复方制剂CPZ/SB(1∶1)及PIPC/TB(8∶1),因此,他唑巴坦起到了增强头孢噻肟对β-内酰胺酶的稳定性和抑酶保护作用。

Objective：To evaluate the relative rate of hydrolysis of cefotaxime/tazobactam（CTX/TB1 ： 1, 2 ： 1, 4 ： 1, 8 ： 1, 16 ： 1 ） 13stariβ-lactamases, which were compared with cefoperazone/sulbactam（CPZ/SB1 ： 1） and piperacillin/tazobactam（PIPC/TB 8 ： 1 ）, and to estimate the ability of tazobactam in preventing hydrolysis of cefotaxime. Methods：The relative rate of hydrolysis of CTX/TB and the ability of enzyme inhibitors in protecting cefotaxime from hydrolyzing byβ-lactamases were measured by biological method. Results：The relative rate of hydrolysis of each combination of CTX/TB was significantly lower than that of CTX alone; Compared with the relative rate of CPZ/SB and PIPC/TB, CTX/TB（ 1 ： 1 ） was lower（ P〈0. 05）, and also lower than CTX/TB（8 ： 1,16 ： 1 ） （P〈 0. 05）. Conclusion： On aspect of inhibition of β-lactamases ,CTX/TB（1 ：1） was better than other combination of CTX/TB, and also better than CPZ/SB and PIPC/TB, therefore, the availability of compounds to cefotaxime and tazobactam could greatly improve the ability of β-lactamases.