【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。更多还原

【Abstract】 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 650T,which carrying qnr positive plasmid.Results All the regimens had excellent bactericidal effects against E.coli J53.The dosages below 500 mg once-daily were insufficient against E.coli 650T and the regrowth bacteria had MICs ranging from 2 mg/L to 4 mg/L,much higher than the parental strains which had MICs of 0.38 mg/L.However,DNA sequencing found no apparent mutations in gyrA and parC of E.coli 650T,which requires further experiments to clarify the underlying mechanism of drug resistance.Conclusions The AUC/MIC ratio of levofloxacin against E.coli 650T should excess 120 to reach an optimal pharmacodynamic endpoint.更多还原