Mi Kun, Sun Da, Li Mei, Hao Haihong, Zhou Kaixiang, Liu Zhenli, Yuan Zonghui, Huang Lingli
National Reference Laboratory of Veterinary Drug Residues (HZAU), Wuhan 430000, China.
MAO Key Laboratory for Detection of Veterinary Drug Residues, Huazhong Agricultural University, Wuhan 430000, China.
Pathogens. 2021 Jan 22;10(2):105. doi: 10.3390/pathogens10020105.
can cause high morbidity and mortality in swine. Cefquinome possesses excellent antibacterial activity against pathogens causing diseases of the respiratory tract. This study aimed to establish the clinical breakpoint (CBP) of cefquinome against and to monitor the resistance change. Referring to the minimum inhibitory concentration (MIC) distribution of cefquinome against 131 isolates, the MIC and MIC were determined to be 0.125 and 1 μg/mL, respectively. And the epidemiological cutoff (ECOFF) value was 1 μg/mL. was selected as a representative strain for the pharmacodynamic (PD) experiment, pharmacokinetic (PK) experiment and clinical experiments. The PK/PD index values, area under concentration-time curve (AUC)/MIC, of the bacteriostatic, bactericidal, and bacterial elimination effects were 23, 41, and 51 h, respectively. The PK/PD cutoff was calculated as 0.125 μg/mL by Monte Carlo simulation (MCS), and the clinical cutoff was 0.25-4 μg/mL by WindoW. Combing these three values, the CBP of cefquinome against was found to be 1 μg/mL. In conclusion, this was the first study to integrate various cutoffs to establish the CBP in the laboratory. It is helpful to distinguish wild type and reduce the probability of treatment failure.
可导致猪的高发病率和死亡率。头孢喹肟对引起呼吸道疾病的病原体具有优异的抗菌活性。本研究旨在确定头孢喹肟对[病原体名称未给出]的临床断点（CBP）并监测耐药性变化。参考头孢喹肟对131株[菌株名称未给出]的最低抑菌浓度（MIC）分布，确定MIC50和MIC90分别为0.125和1μg/mL。且流行病学临界值（ECOFF）为1μg/mL。[菌株名称未给出]被选为药效学（PD）实验、药代动力学（PK）实验和临床试验的代表性菌株。抑菌、杀菌和细菌清除作用的药代动力学/药效学（PK/PD）指数值，即浓度-时间曲线下面积（AUC）/MIC，分别为23、41和51小时。通过蒙特卡洛模拟（MCS）计算得出PK/PD临界值为0.125μg/mL，通过WindoW得出临床临界值为0.25 - 4μg/mL。综合这三个值，发现头孢喹肟对[菌株名称未给出]的CBP为1μg/mL。总之，这是首次在实验室中整合各种临界值来确定CBP的研究。有助于区分野生型[菌株名称未给出]并降低治疗失败的概率。
