摘要
目的:评价不同质量配比的头孢噻肟-舒巴坦的体内抗菌活性,为寻找其合理配比提供依据。方法:小鼠腹腔注射0.5 mL的1个最小致死量(MLD)菌液(金葡球菌、大肠埃希菌、肺炎克雷伯菌、阴沟肠杆菌)建立败血症模型,感染1 h后注射给予0.2 mL不同浓度的药液(每种药物配比5~6组,每组10只鼠),观察和记录感染鼠死亡率(共7 d)。用NDST软件程序的Bliss法计算半数有效量(ED_(50))值和95%有效量(ED_(95))值、ED_(50)的95%可信限,用t检验比较各药ED_(50)值。结果:头孢噻肟-舒巴坦在1:1,2:1和4:1质量配比时对大肠埃希菌、肺炎克雷伯菌产超广谱β内酰胺酶(ESBLs)菌株的体内抗菌作用显著优于头孢噻肟-舒巴坦(8:1)及头孢噻肟单剂,ED_(50)值及ED_(95)值仅为头孢噻肟单剂的1/6.6~1/2.0及1/6.9~1/1.4(P<0.01)。头孢噻肟-舒巴坦在1:1和2:1配比时对产酶阴沟肠杆菌感染小鼠体内抗菌作用优于4:1和8:1配比及头孢噻肟单剂,ED_(50)值及ED_(95)值仅为头孢噻肟单剂1/5.2~1/4.2及1/3.6~1/2.0(P<0.01)。头孢噻肟-舒巴坦在1:1,2:1,4:1和8:1配比时对产酶金葡球菌感染小鼠体内抗菌作用与头孢噻肟单剂相似。结论:头孢噻肟-舒巴坦在1:1和2:1配比时对大肠埃希菌、肺炎克雷伯ESBLs菌株及产酶阴沟肠杆菌感染小鼠体内抗菌作用最强。头孢噻肟-舒巴坦2:1配比可减少舒巴坦用药量,为最佳配方组合。
Objective:To evaluate the in vivo antibacterial effects of combination of sulbactam with cefotaxim (1: 1, 2: 1,4:1 and 8:1 ) in the treatment of mice septicemia caused by the pathogenic microorganisms producing extended-speetrum beta-lactamases(ESBLs). Methods: A mouse septicemia model was set up by an abdominal injection with 0. 5 mL minimum lethal dose of methicillin-resistant Staphylococcus aureus( MRSA ) ,Escherichia coli ( E. coli ) ,Klebsiella pneumoniae( Kl. pneumoniae ) and Enterobacter cloacae (Ent. cloacae). The different concentrations of combination antibiotics (0.2 mL each injection) were injected once into the mice in 1 hour after the injection of bacteria. Each combination antibiotics were tested in 5 -6 concentration groups, and each group was consisted of 10 mice. The death rate in each infected mice group was monitored. The EDso ,ED95 and L95 were calculated using a bliss method of NDST software. The t test was used to determine the statistical significance of ED50. Results: The combination of cefotaxim with sulbactam at the ratio of 1: 1,2: 1 and 4:1 showed a superiority against E. coli,Kl, pneumoniae and Ent. cloacae to the one at 1 : 8 and cefotaxim alone, the ED 50 and ED 95 values of the combination of sulbactam with cefotaxim (1: 1, 2:1 and 4: 1) against the mouse septicemia by E. coli and Kl. pneumoniae were 1/6. 6 - 1/2. 0 and 1/6. 9 - 1/1.4 times of cefotaxim alone (P 〈0.01 ). The combination of sulbactam with cefotaxim (1:1 and 2:1 ) against the mouse septicemia by Ent. cloacae were 1/5.2 - 1/4.2 and 1/3.6 - 1/2. 0 times of the ones at the ratio of 4:1 and 8:1 and cefotaxim alone (P 〈 0. 01 ). The combination of sulbactam with cefotaxim (1: 1, 2: 1, 4:1 and 8: 1) against the mouse septicemia by MRSA showed no difference from cefotaxim alone (P 〉 0. 05 ). Conclusion: The combination of sulbactam with cefotaxim (1:1 and 1: 2) had the most potent antibacterial activity. In the viewpoint of the combination, the optimal ratio of sulbactam to cefotaxim is 1:2.
出处
《中国新药杂志》
CAS
CSCD
北大核心
2006年第4期269-273,共5页
Chinese Journal of New Drugs
关键词
头孢噻肟
舒巴坦
败血症模型
体内抗菌作用
超广谱Β内酰胺酶
cefotaxim
sulbctam
mouse septicemia model
in vivo antibacterial activity
extended-spectrum beta-lactamases