【摘要】 目的不同配比头孢呋辛/三唑巴坦对产酶菌感染小鼠所致败血症的治疗作用研究,比较头孢呋辛/三唑巴坦(1:1、2:1、4:1和8:1)各种配比的抗菌活性及评价其合理性,为新药研制提供理论依据。方法通过腹腔注射0.5ml的1个最小致死量(MLD)菌液感染小鼠建立小鼠败血症模型。感染1h后给被感染小鼠注射0.2ml不同浓度的抗菌药液(每种药物配比5组,每组10只小鼠),观察和记录感染鼠死亡率(共7d)。ED50值、ED95值、ED5095%可信限及各药ED50值的t检验结果P值均用NDST软件程序的Bliss法计算统计。比较头孢呋辛/三唑巴坦(1:1、2:1、4:1和8:1)配比对实验的产超广谱β-内酰胺酶(ESBLs)的大肠埃希菌、肺炎克雷伯菌株及对甲氧西林敏感的金葡菌产酶菌(MSSA)感染小鼠所致败血症的治疗作用。结果头孢呋辛/三唑巴坦(1:1和2:1)配比对大肠埃希菌、肺炎克雷伯菌产ESBLs菌株的体内抗菌作用显著优于头孢呋辛/三唑巴坦(4:1和8:1)及单剂;ED50值及ED95值分别为头孢呋辛单剂的2.32～3.29和1.81～3.35倍(P<0.01)。头孢呋辛/三唑巴坦(1:1、2:1和4:1)配比对实验的产酶MSSA感染小鼠败血症治疗作用显著优于头孢呋辛/三唑巴坦(8:1)及单剂,ED50值及ED95值分别为头孢呋辛单剂1.56～3.33和2.24～4.03倍(P<0.01,0.01<P<0.05)。头孢呋辛/三唑巴坦(1:1、2:1)对实验的产ESBLs大肠埃希菌、肺炎克雷伯菌、产酶MSSA菌株感染小鼠败血症治疗作用类似(P>0.05)。结论在所有实验药中,头孢呋辛/三唑巴坦(1:1和2:1)对实验的大肠埃希菌、肺炎克雷伯菌ESBLs、产酶MSSA菌株感染小鼠败血症治疗作用显著优于头孢呋辛/三唑巴坦(4:1和8:1)及头孢呋辛单剂;与1:1的比例相比,头孢呋辛/三唑巴坦(2:1)配比抗菌作用相似并可减少三唑巴坦用药量,降低用药费用及用药不良反应产生的机率。体内试验结果显示头孢呋辛/三唑巴坦(2:1)合剂为最佳配方组合。更多还原

【Abstract】 Objective To evaluate the in vivo activity of different combination of cefuroxime and tazobactam in the treatment of mouse septicemia caused by β-lactamases producing clinical isolates.Methods The mouse septicemia model was established by an intraperitoneal injection with 0.5ml suspensions(minimal lethal dose) of ESBLs-producing E.coli,Klebsiella pneumoniae and β-lactamases producing MSSA.Different-concentration combinations of cefuroxime and tazobactam were injected to the mice in an hour after the injection of the bacterial suspensions.Each antibiotic combination was tested in five concentration groups,and each group consisted of 10 mice.The death rate in each group was monitored.The ED50,ED95,95% confidence intervals and P values were calculated using a Bliss method of NDST software.Results The combinations of cefuroxime with tazobactam(1:1 and 2:1) showed stronger activities against E.coli and K.pneumoniae than those of the ratio at 4:1,8:1 and cefuroxime alone,and the ED50 and ED95 values of the combination of cefuroxime with tazobactam(1:1 and 2:1) against the mouse septicemia caused by E.coli and K.pneumoniae were 2.32～3.29 and 1.81～3.35 times of those of cefuroxime alone(P<0.01).The combina-tions of cefuroxime with tazobactam(1:1,2:1 and 4:1) showed higher activities against E.coli and K.pneumoniae than those of the ratio at 8:1 and cefuroxime alone,and the ED50 and ED95 values of the combination of cefuroxime with tazobactam(1:1,2:1 and 4:1) against the mouse septicemia caused by E.coli and K.pneumoniae were 1.56～3.33 and 2.24～4.03 times of those of cefuroxime alone(P<0.01).Conclusion The combination of cefuroxime with tazobactam(1:1 and 2:1) showed significant antibacterial activity in mouse septicemia caused by β-lactamases producing strains and the optimal combination ratio of cefuroxime and tazobactam was 2:1.更多还原