Journal of Integrative Agriculture ›› 2021, Vol. 20 ›› Issue (7): 1921-1932.DOI: 10.1016/S2095-3119(20)63572-9

所属专题： 动物医学合辑Veterninary Medicine

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  • 收稿日期:2020-07-15 出版日期:2021-07-01 发布日期:2021-06-02

Susceptibility breakpoint for cefquinome against Escherichia coli and Staphylococcus aureus from pigs

ZHANG Hui-lin*, ZHAO Yi-yang*, ZHOU Zi-chong, DING Huan-zhong
  

  1. Guangdong Key Laboratory for Veterinary Drug Development and Safety Evaluation, South China Agricultural University, Guangzhou 510000, P.R.China
  • Received:2020-07-15 Online:2021-07-01 Published:2021-06-02
  • Contact: Correspondence DING Huan-zhong, Tel/Fax: +86-20-85282562, E-mail: hzding@scau.edu.cn
  • About author:ZHANG Hui-lin, E-mail: hlzhang@stu.scau.edu.cn; * These authors contributed equally to this study.
  • Supported by:
    This work was supported by the National Natural Science Foundation of China (31972733).

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摘要：

头孢喹肟是动物专用的第四代头孢菌素类药物，对大肠杆菌和金黄色葡萄球菌均有较好的作用效果。本研究旨在建立头孢喹肟对大肠杆菌和金黄色葡萄球菌的野生型折点（wild-type cut-off, COWT）和药动/药效学折点（pharmacokinetic/pharmacodynamic, COPD），以期为临床细菌耐药性监测提供数据指导。采用微量肉汤稀释法测定2014至2018年期间广东省分离的210株猪源大肠杆菌和160株猪源金黄色葡萄球菌对头孢喹肟的最低抑菌浓度（minimum inhibitory concentration, MIC），结果表明头孢喹肟对大肠杆菌的MIC50（能抑制50%细菌生长的最低药物浓度和MIC90（能抑制90%细菌生长的最低药物浓度）分别是0.06 μg mL-1和0.25 μg mL-1；对金黄色葡萄球菌的MIC50和MIC90分别是0.5 μg mL-1 和1 μg mL-1。统计学分析方法和ECOFFinder程序计算结果表明头孢喹肟对大肠杆菌和金黄色葡萄球菌的野生型折点分别为0.125 μg mL-1和2 μg mL-1。大肠杆菌和金黄色葡萄球菌对头孢喹肟的耐药率分别为11.9％和6.25％。基于5000次循环的蒙特卡洛计算结果显示在临床推荐给药剂量下（2 mg kg-1,每天给药2次，连续给药3天），头孢喹肟对大肠杆菌和金黄色葡萄球菌的药动/药效学折点值均为0.25 µg mL-1，表明在当前推荐剂量下可对MIC ≤ 0.25 μg mL-1的大肠杆菌和金黄色葡萄球菌实现90％以上的有效治疗。当前的给药方案对金黄色葡萄球菌引起的感染不能取得理想的治疗效果，将头孢喹肟给药剂量调整为4.5 mg kg-1时，能对MIC90 = 1 μg mL-1的金黄色葡萄球菌引起的感染实现90%以上的有效治疗。本研究对于临床上头孢喹肟对猪源大肠杆菌和金黄色葡萄球菌的耐药性监测和用药指导有重要意义。


Abstract:

Cefquinome is the only fourth-generation cephalosporin used solely for veterinary applications.  In this study, we established the wild-type cut-off (COWT) and pharmacokinetic/pharmacodynamic cut-off (COPD) of cefquinome against Escherichia coli and Staphylococcus aureus.  A total of 210 E. coli and 160 S. aureus isolates were collected from pigs in Guangdong Province between 2014 and 2018.  The minimum inhibitory concentrations (MICs) were determined using a microdilution broth method.  MIC50 and MIC90 were 0.06 and 0.25 μg mL–1 for E. coli and 0.5 and 1 μg mL–1 for S. aureus, respectively.  Statistical analysis and the ECOFFinder Program showed that the COWT for cefquinome against E. coli and S. aureus were 0.125 and 2 µg mL–1, respectively.  The resistance rates were 11.9% for E. coli and 6.25% for S. aureus.  Based on a 5 000-subject Monte Carlo simulation, the COPD value for cefquinome against E. coil and S. aureus was 0.25 µg mL–1 under the recommended dose (2 mg kg–1, twice a day for 3 days), confirming that infections caused by strains with MIC≤0.25 μg mL–1 could be effectively treated.  Following adjustment of the dosing regimen to 4.5 mg kg–1, effective treatment (>90) was achieved for S. aureus infections with MIC90 1 μg mL–1.  This susceptibility breakpoint determination is significant for resistant surveillance and cefquinome dosage guidance against E. coli and S. aureus in pigs.

Key words: cefquinome ,  Escherichia coli ,  Staphylococcus aureus ,  COWT ,  COPD