β-内酰胺类抗生素对产ESBL肺炎克雷伯菌小鼠肺炎疗效研究  

Efficacy of different β-lactams against two extended spectrum β-lactamase producing Klebsilla pneumoniae strains in a mouse model of pneumonia

作　　者：裴迎华[1] 张杰[1] 马越[2] 李景云[2] 

机构地区：[1]首都医科大学附属天坛医院,北京100050 [2]中国药品生物制品检定所,北京100050

出　　处：《中国抗生素杂志》2008年第1期30-33,共4页Chinese Journal of Antibiotics

摘　　要：目的评价几种β-内酰胺类抗生素对不同的产超广谱β-内酰胺酶(ESBL)肺炎克雷伯菌动物肺炎模型的疗效。方法选择临床分离的2株对实验用抗生素敏感的产ESBL肺炎克雷伯菌建立小鼠肺炎模型。根据细菌分为GX6998和Tian29两组,于感染后6h给药。对照组腹腔注射生理盐水0.5ml;治疗组分别给予头孢哌酮/舒巴坦、头孢他啶、头孢吡肟和哌拉西林/三唑巴坦。连续治疗72h后,根据细菌计数结果评价疗效。结果体外药敏试验表明Tian29对4种抗生素的MIC值均大于GX6998,但仍在敏感范围内。4种抗生素治疗后,各组病死率均显著减低。GX6998组中4种抗生素均可显著降低肺组织匀浆的细菌计数(P<0.01)。Tian29组中头孢哌酮/舒巴坦、头孢他啶可以显著降低肺组织匀浆的细菌计数(P<0.05);头孢吡肟和哌拉西林/三唑巴坦也可使组织匀浆的细菌计数减少,但与对照组比较差异无显著性(P>0.05)。比较同一种抗生素对2株细菌的清除作用发现,4种抗生素对GX6998的清除作用均强于Tian29(P<0.01)。结论体外敏感的广谱β-内酰胺类抗生素和β-内酰胺酶抑制剂复合制剂治疗产ESBL肺炎克雷伯菌感染均可显著降低动物模型的死亡率,减少肺组织匀浆细菌计数。但如果细菌对抗生素的MIC升高,将会影响治疗效果。Objective To evaluate the efficacy of several β-1actams against ESBL producing Klebsiella pneurnoniae pneumonia in a mouse model of peneumonia. Methods Two clinical Klebsiella pneumoniae strains susceptible to the experimental antimicrobial agents, Klebsiella pneumoniae GX6998 and Tian 29, were divided into two groups for mouse pneumonia infection respectively. After six-hour infection, mice were intraperitoneally injected with 0. 5ml 0. 9% NaC1 for control; mice were intraperitoneally injected with ceftazidime, cefepime, cefoprazone plus sulbactam and piperacillin plus tazobactam respectively for trial. Seventy-two hours latcr, therapy efficacies were evaluated with bacterial counts. Results All the trial groups had significantly lower mortality than control groups （P〈0.05）. Compared with the control groups, in GX6998-infected groups, the bacterial amounts with all the testing agents were significantly decreased （P〈 0.01）; in Tian 29-infected group, the bacterial amounts with ccfoprazonc plus sulbactam and ceftazidimc were significantly decreased （P〈0.05）; in cefcpime and pipcraciltin plus tazobactam groups, bacterial amounts were reduced without significant difference with that of the control group （P〉0.05）. Conclusion The combinations of broad-spectrum β-lactams and β-lactamases inhibitor could reduce the mortality and bacterial amounts in mouse pneumonia model which were susceptible to ESBLs-producing Klebsiella pneumonia strains. However, the clinical efficacy would be reduced when the MIC increased.

关 键 词：超广谱Β-内酰胺酶 Β-内酰胺类抗生素 肺炎克雷伯菌 药效学 

分 类 号：R378[医药卫生—病原生物学]