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首页> 美国卫生研究院文献>Antimicrobial Agents and Chemotherapy >Levofloxacin plus Metronidazole Administered Once Daily versus Moxifloxacin Monotherapy against a Mixed Infection of Escherichia coli and Bacteroides fragilis in an In Vitro Pharmacodynamic Model
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Levofloxacin plus Metronidazole Administered Once Daily versus Moxifloxacin Monotherapy against a Mixed Infection of Escherichia coli and Bacteroides fragilis in an In Vitro Pharmacodynamic Model

机译：左氧氟沙星加甲硝唑每日一次与莫西沙星单一疗法在体外药效学模型中对大肠杆菌和脆弱拟杆菌的混合感染进行比较

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Moxifloxacin has been suggested as an option for monotherapy of intra-abdominal infections. Recent data support the use of a once-daily metronidazole regimen. The purpose of this study was to investigate the activity of levofloxacin (750 mg every 24 h [q24h]) plus metronidazole (1,500 mg q24h) compared with that of moxifloxacin (400 mg q24h) monotherapy in a mixed-infection model. By using an in vitro pharmacodynamic model in duplicate, Escherichia coli and Bacteroides fragilis were exposed to peak concentrations of 8.5 mg of levofloxacin/liter q24h, 32 mg of metronidazole/liter q24h, and 2 mg for moxifloxacin/liter q24h for 24 h. The activities of levofloxacin, metronidazole, moxifloxacin, and levofloxacin plus metronidazole were evaluated against E. coli, B. fragilis, and E. coli plus B. fragilis. The targeted half-lives of levofloxacin, metronidazole, and moxifloxacin were 8, 8, and 12 h, respectively. Time-kill curves were analyzed for time to 3-log killing, slope, and regrowth. Pre- and postexposure MICs were determined. The preexposure levofloxacin, metronidazole, and moxifloxacin MICs for E. coli and B. fragilis were 0.5 and 1, >64 and 0.5, and 1 and 0.25 mg/liter, respectively. Levofloxacin and moxifloxacin achieved a 3-log killing against E. coli and B. fragilis in all experiments, as did metronidazole against B. fragilis. Metronidazole did not decrease the starting inoculum of E. coli. The area under the concentration-time curve/MIC ratios for E. coli and B. fragilis were 171.7 and 85.9, respectively, for levofloxacin and 26 and 103.9, respectively, for moxifloxacin. Levofloxacin plus metronidazole exhibited the fastest rates of killing. The levofloxacin and moxifloxacin MICs for B. fragilis increased 8- to 16-fold after the organism was exposed to moxifloxacin. No other changes in the postexposure MICs were found. Levofloxacin plus metronidazole administered once daily exhibited activity similar to that of moxifloxacin against the mixed E. coli and B. fragilis infection. A once-daily regimen of levofloxacin plus metronidazole looks promising for the treatment of intra-abdominal infections.
机译：已建议将莫西沙星作为腹腔内感染单一疗法的选择。最新数据支持每天使用一次甲硝唑治疗方案。这项研究的目的是在混合感染模型中研究左氧氟沙星（每24 h [q24h] 750 mg）加甲硝唑（1,500 mg q24h）与莫西沙星（400 mg q24h）单一疗法的活性。通过一式两份使用体外药效学模型，将大肠杆菌和脆弱拟杆菌（Bacteroides fragilis）的峰值浓度分别暴露于8.5 mg左氧氟沙星/升q24h，32 mg甲硝唑/升q24h和2 mg莫西沙星/升q24h。评估了左氧氟沙星，甲硝唑，莫西沙星和左氧氟沙星加甲硝唑对大肠杆菌，脆弱型芽孢杆菌和大肠杆菌加脆弱型芽孢杆菌的活性。左氧氟沙星，甲硝唑和莫西沙星的目标半衰期分别为8、8和12小时。分析了时间杀灭曲线的杀灭时间，3-log杀灭，斜率和再生长。确定了暴露前和暴露后的MIC。暴露前的左氧氟沙星，甲硝唑和莫西沙星的MIC分别为0.5和1，> 64和0.5、1和0.25 mg / L，分别为0.5和1。左氧氟沙星和莫西沙星在所有实验中均能对大肠杆菌和脆弱的B. gilgilis杀灭3-log，甲硝唑对脆弱的B. giltis也是如此。甲硝唑不会降低大肠杆菌的起始接种量。左氧氟沙星的大肠杆菌和脆弱的芽孢杆菌的浓度-时间曲线/ MIC比值下的面积分别为171.7和85.9，莫西沙星分别为26和103.9。左氧氟沙星加甲硝唑的杀灭速度最快。暴露于莫西沙星后，脆弱类杆菌的左氧氟沙星和莫西沙星的MICs增加了8到16倍。没有发现暴露后MIC的其他变化。每天服用左氧氟沙星加甲硝唑对混合大肠杆菌和 B的活性类似于莫西沙星。脆弱的感染。左氧氟沙星加甲硝唑的每日一次治疗方案有望用于治疗腹腔内感染。

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