头孢噻肟和舒巴坦复方制剂体内外抗菌活性研究  

In vitro and in vivo synergistic antibacterial activity of cefotaxime/sulbactam

作　　者：杨文吉[1] 邵振俊[1] 曾云[1] 罗刚[1] 周黎明[1] 

机构地区：[1]四川大学华西基础医学与法医学院,成都610041

出　　处：《中国抗生素杂志》2008年第8期487-490,共4页Chinese Journal of Antibiotics

摘　　要：目的评价头孢噻肟钠/舒巴坦钠(CTX/SB,1∶1,2∶1,4∶1,8∶1,16∶1)及单组分头孢噻肟钠(CTX)对13株产β-内酰胺酶革兰阴性菌体外抗菌作用,并与复方制剂头孢哌酮钠/舒巴坦钠(CPZ/SB 1∶1)和哌拉西林钠/三唑巴坦钠(PIPC/TB 8∶1)进行比较,以及对产酶大肠埃希菌与铜绿假单胞菌感染小鼠体内保护作用。方法采用琼脂二倍稀释法测定CTX/SB(1∶1,2∶1,4∶1,8∶1,16∶1)复方制剂对产β-内酰胺酶革兰阴性菌体外抗菌作用及对产酶大肠埃希菌与铜绿假单胞菌感染小鼠体内保护作用;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,PCR扩增并检测了其耐药酶的类型。结果CTX/SB(1∶1)的MICs较CTX有不同程度的下降;各不同配比CTX/SB的相对水解率均显著低于CTX单用(P<0.01),CTX/SB(1∶1)的相对水解率也显著低于PIPC/TB(8∶1)和CPZ/SB(1∶1)(P<0.01);CTX/SB(1∶1)的抑酶保护率显著低于CTX/SB(8∶1,16∶1)(P<0.01),也低于CTX/SB(2∶1,4∶1),但无统计学意义。体内试验,CTX/SB(1∶1)的ED50值较CTX有明显下降。结论体内、外试验表明CTX/SB(1∶1)抑酶效应优于其它配比,也优于同类复方制剂CPZ/SB(1∶1)及PIPC/TB(8∶1);因此,舒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 in vitro synergistic activity of cefotaxime/sulbactam （CTX/SB, 1 ： 1, 2 ： 1, 4 ： 1, 8 ： 1, 16 ： 1） against 13 stains producing β-lactamases, and compare with cefotaxime, cefoperazone/sulbactam （CPZ/SB, 1 ： 1）and piperacillin/tazobactam （PIPC/TB, 8： 1）; as well as compare the in vivo antibacterial activity between cefotaxime and CTX/SB （1 ： 1）. Methods The minimal inhibitory concentrations were detected by the agar dilution method. The hydrolysis rate and the ability of enzyme inhibitor in protecting cefotaxime from hydrolyzing by β-lactamases were measured by biological method. The in vivo antibacterial activities of CTX/SB （1 ： 1） and cefotaxime were detected on mice in experimental infection caused by P. aeruginosa 39 and E. coli 8. Results The relative rate of hydrolysis of each combination of CTX/SB was significantly lower than that of CTX alone （P〈0. 01）. The relative rate of hydrolysis of CTX/SB （1 ： 1） was also remarkably lower than CPZ/SB and PIPC/TB （P〈0.01）. The inhibition rate of β-lactamases of CTX/SB （1 ： 1） was lower than that of CTX/SB （8 ： 1, 16 ： 1） （P〈0.05）; the ED50 value of CTX/SB （1 ： 1） was also lower than that of cefotaxime. Conclusion In respect to the inhibition of β-lactamases, CTX/SB （1 ： 1） was better than other combination of CTX/SB, and also CPZ/SB and PIPC/TB, therefore, the hydrolysis activity of β-lactamases was greatly improved by the combination of compounds cefotaxime and sulbactam.

关 键 词：头孢噻肟 舒巴坦 最低抑菌浓度 生物法 半数有效量 

分 类 号：R978.11[医药卫生—药品]