AIM: Bacterial resistance to quinolones has traditionally mediated by alteration of the quinolone targets and/or overproduction of efflux pump. Recently, a new mechanism, the plasmid-mediated quinolone resistance name...AIM: Bacterial resistance to quinolones has traditionally mediated by alteration of the quinolone targets and/or overproduction of efflux pump. Recently, a new mechanism, the plasmid-mediated quinolone resistance named qnr, has been clarified. Qnr and its homologus are widely distributed among gram-negative bacteria. The presence of qnr only slightly elevates the resistance level, however it facilitates the selection of highly resistant strains. In our study, we examined the probable influence of such phenomenon to the clinical regimens of levofloxacin. METHODS: In-vitro hollow fiber infection model simulating oral two-compartment pharmacokinetic model was established. In the model, bacteria was incubated in the peripheral compartment without ‘washout effect’. We designed two therapeutic regimens of levofloxacin, including 500 mg qd (peak 5.12 mg/L; half-time 6.9 h) and 700 mg qd (peak 9.46 mg/L; half-time 6.9 h) for 3 days against E.coli J53 and E. coli 6503, which carrying qnr positive plasmid. RESULTS: Although 500 mg qd regimen could decrease the bacteria density of E. coli 6503 at the beginning, the bacteria population bounced back when the drug concentration was drecreased below 2 mg/L, and the regrowth bacteria had higher MICs than the parental strains. 700 mg qd for 3 days could inhibit the outgrowth of E. coli 6503 all the time. E. coli J53 was well inhibited by both the mentioned therapeutic regimens. DNA sequencing found the mutations in QRDR of E. coli 6503. CONCLUSION: We conclude that 500 mg qd which is the most popular regimen is at risk of selecting resistant mutations and treatment failure while treating the infections caused by qnr positive E. coli, and 750 mg qd might be preferred. In vivo pharmacodynamic studies to support our findings are warranted.展开更多
为探明宠物在抗微生物药物耐药性(AMR)传播中的作用,上海交通大学医学院-国家热带病研究中心全球健康学院与上海市动物疫病预防控制中心合作,首次在上海开展大规模宠物犬猫耐药菌监测。研究成果“Companion animals as sources of hazar...为探明宠物在抗微生物药物耐药性(AMR)传播中的作用,上海交通大学医学院-国家热带病研究中心全球健康学院与上海市动物疫病预防控制中心合作,首次在上海开展大规模宠物犬猫耐药菌监测。研究成果“Companion animals as sources of hazardous critically important antimicrobial-resistant Escherichia coli:genomic surveillance in Shanghai”于2025年3月10日发表于权威期刊Journal of Hazardous Materials。展开更多
文摘AIM: Bacterial resistance to quinolones has traditionally mediated by alteration of the quinolone targets and/or overproduction of efflux pump. Recently, a new mechanism, the plasmid-mediated quinolone resistance named qnr, has been clarified. Qnr and its homologus are widely distributed among gram-negative bacteria. The presence of qnr only slightly elevates the resistance level, however it facilitates the selection of highly resistant strains. In our study, we examined the probable influence of such phenomenon to the clinical regimens of levofloxacin. METHODS: In-vitro hollow fiber infection model simulating oral two-compartment pharmacokinetic model was established. In the model, bacteria was incubated in the peripheral compartment without ‘washout effect’. We designed two therapeutic regimens of levofloxacin, including 500 mg qd (peak 5.12 mg/L; half-time 6.9 h) and 700 mg qd (peak 9.46 mg/L; half-time 6.9 h) for 3 days against E.coli J53 and E. coli 6503, which carrying qnr positive plasmid. RESULTS: Although 500 mg qd regimen could decrease the bacteria density of E. coli 6503 at the beginning, the bacteria population bounced back when the drug concentration was drecreased below 2 mg/L, and the regrowth bacteria had higher MICs than the parental strains. 700 mg qd for 3 days could inhibit the outgrowth of E. coli 6503 all the time. E. coli J53 was well inhibited by both the mentioned therapeutic regimens. DNA sequencing found the mutations in QRDR of E. coli 6503. CONCLUSION: We conclude that 500 mg qd which is the most popular regimen is at risk of selecting resistant mutations and treatment failure while treating the infections caused by qnr positive E. coli, and 750 mg qd might be preferred. In vivo pharmacodynamic studies to support our findings are warranted.
文摘为探明宠物在抗微生物药物耐药性(AMR)传播中的作用,上海交通大学医学院-国家热带病研究中心全球健康学院与上海市动物疫病预防控制中心合作,首次在上海开展大规模宠物犬猫耐药菌监测。研究成果“Companion animals as sources of hazardous critically important antimicrobial-resistant Escherichia coli:genomic surveillance in Shanghai”于2025年3月10日发表于权威期刊Journal of Hazardous Materials。
