左氧氟沙星对携带qnrA1基因大肠埃希菌药动学-药效学研究  

In vitro pharmacokinetics and pharmacodynamics of levofloxacin against Escherichia coli expressing plasmid-mediated quinolone resistant determinant qnrA1

作　　者：徐俊芳[1] 徐晓刚[1] 王明华[1] 施耀国[1] 张菁[1] 王明贵[1] 张婴元[1] 

机构地区：[1]复旦大学附属华山医院抗生素研究所,上海200040

出　　处：《中国感染与化疗杂志》2008年第4期250-254,共5页Chinese Journal of Infection and Chemotherapy

摘　　要：目的探讨左氧氟沙星对携带qnrA1质粒大肠埃希菌感染的合理给药方案。方法根据左氧氟沙星药动学参数构建左氧氟沙星体外药动学-药效学模型。在体外感染模型中研究左氧氟沙星200、300、500、550和700mg每日1次对大肠埃希菌J53(不含qnr质粒)和大肠埃希菌650T(含qnr质粒的J53结合子)的药效学,制定体外药动学-药效学目标值。结果左氧氟沙星上述5个剂量组对大肠埃希菌J53均有良好的杀灭作用;500mg每日1次及以下剂量组均不能有效杀灭大肠埃希菌650T。用药结束后左氧氟沙星对细菌的MIC由给药前的0.4mg/L平均升高到2~4mg/L。但DNA测序并未发现喹诺酮耐药决定区(QRDR)存在突变,细菌MIC上升的原因有待进一步研究。结论体外药动学-药效学研究提示左氧氟沙星对携带qnr质粒大肠埃希菌的AUC/MIC需达到120或以上时方能有效抑制细菌的生长。Objective To explore the optimal pharmacodynamic regimen of levofloxacin against qnr-positive E.coli.Methods In-vitro hollow fiber infection model simulating oral two-compartment pharmacokinetic profile of levofloxacin was established.In the model,bacteria were incubated in the peripheral compartment without ′washout effect′.We designed five therapeutic regimens,including 200 mg,300 mg,500 mg,550 mg and 700 mg of levofloxacin to study the pharmacodynamic target of levofloxacin against E.coli J53 and E.coli ...

关 键 词：左氧氟沙星 药动学-药效学 质粒介导喹诺酮耐药 

分 类 号：R96[医药卫生—药理学]