Institute of Biomedicine of Seville, University Hospital Virgen del Rocío/CSIC/University of Seville, Seville, Spain.
J Antimicrob Chemother. 2013 Jul;68(7):1609-15. doi: 10.1093/jac/dkt063. Epub 2013 Mar 14.
The aim of this study was to evaluate the impact of qnrA1, qnrB1 and qnrS1 on the in vivo efficacies of ciprofloxacin and levofloxacin in an experimental model of pneumonia caused by Escherichia coli.
Two isogenic groups of E. coli transformants, based on two ATCC 25922 strains, with or without the GyrA mutation Ser83Leu, and carrying qnrA1, qnrB1 or qnrS1, were used in an experimental pneumonia model. The efficacies of ciprofloxacin (40 mg/kg/day) and levofloxacin (50 and 150 mg/kg/day) were evaluated.
For the pneumonia caused by the parental strains lacking qnr genes, both fluoroquinolones significantly (P<0.05) reduced the bacterial lung concentration by >7 log10 cfu/g against E. coli ATCC/pBK and between 5.09 and 6.34 log10 cfu/g against E. coli ATCC-S83L/pBK. The presence of any qnr genes in the strains of both isogenic groups diminished the reduction of bacterial lung concentration with any therapy (P<0.05). Furthermore, all therapeutic schemes reduced the percentage of positive blood cultures in both isogenic groups (P<0.05). Finally, the survival results suggest a higher mortality with the strains expressing qnr genes.
The presence of qnrA1, qnrB1 and qnrS1 in E. coli reduced the efficacy of ciprofloxacin and levofloxacin in a murine pneumonia model.
本研究旨在评估 qnrA1、qnrB1 和 qnrS1 对大肠杆菌引起的肺炎实验模型中环丙沙星和左氧氟沙星体内疗效的影响。
使用基于两个 ATCC 25922 株的两种同源转化体大肠杆菌，分别带有或不带有 GyrA 突变 Ser83Leu，并携带 qnrA1、qnrB1 或 qnrS1，用于肺炎实验模型。评估环丙沙星（40mg/kg/天）和左氧氟沙星（50 和 150mg/kg/天）的疗效。
对于缺乏 qnr 基因的亲本菌株引起的肺炎，两种氟喹诺酮类药物均显著（P<0.05）降低了大肠杆菌 ATCC/pBK 的细菌肺浓度>7log10cfu/g，并且降低了大肠杆菌 ATCC-S83L/pBK 的细菌肺浓度 5.09 至 6.34log10cfu/g。两种同源转化体菌株中任何 qnr 基因的存在均降低了任何治疗方案对细菌肺浓度的降低（P<0.05）。此外，所有治疗方案均降低了两种同源转化体中阳性血培养的百分比（P<0.05）。最后，生存结果表明，表达 qnr 基因的菌株的死亡率更高。
qnrA1、qnrB1 和 qnrS1 在大肠杆菌中的存在降低了环丙沙星和左氧氟沙星在肺炎实验模型中的疗效。
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