Study On The Susceptible Breakpoint For Cefquinome Against E.coli And Staphylococcus Aureus From Pigs

Cefquinome is a fourth-generation cephalosporin which has been developed solely for veterinary use.It has a fairly broad spectrum of efficacy and shows good antibacterial activity against E.coil and Staphylococcus aureus.However,there is no breakpoint about Cefquinome on CLSI and EUCAST standard.And the lack of interpretive criteria seriously affects the development of drug resistance monitoring for Cefquinome.In this study,we established Wild type cut-off(CO_WT)and PK/PD cut-off(CO_PD)of Cefquinome against E.coil and Staphylococcus aureus.The finding in this study provided theory basis and data support for the development of drug resistance monitoring.A total of 210 E.coli and 160 Staphylococcus aureus isolates were collected from pigs in Guangdong Province from 2014 to 2018.MIC was determined by broth micro dulution technique detailed by the EUCAST.Using Normal distribution test and nonlinear regression method to determine CO_WT.Cefquinome CO_WTfor E.coli is 0.125μg/m L.Cefquinome CO_WTfor Staphylococcus aureus is 2μg/m L.The result of antimicrobial sensitivity test showed that E.coil and Staphylococcus aureus were resistant to Cefquinome11.9%and 6.25%.The PK/PD data were obtained from in vivo tissue-cage model studies.The correlation coefficient between%T>MIC and antibacterial effect was 0.90,suggesting the most important PK/PD parameter was%T>MIC.E.coil and Staphylococcus aureus of%T>MIC predicted for continuous 1/2-log reduction were 52.68%and 42.91%.A 5000-subject Monte Carlo simulation was used to calculate the CO_PDof Cefquinome against E.coil and Staphylococcus aureus using R software,based on the PK parameters from pigs,MIC distribution and the PK/PD targets.The results show that Cefquinome CO_PDfor E.coil and Staphylococcus aureus were 0.25μg/m L.According to CLSI regulations,when no clinical cut-off(CO_CL)was built,CO_PDwas the final breakpoint.So in this paper,the breakpints of Cefquinome against E.coil and Staphylococcus aureus are 0.25μg/m L.