AUTHOR=Li Yafei , Feng Baoyi , Gu Xiaoyan , Yang Dawei , Zeng Zhenling , Zhang Bingxu , Ding Huanzhong 

TITLE=Correlation of PK/PD Indices with Resistance Selection for Cefquinome against Staphylococcus aureus in an In Vitro Model

JOURNAL=Frontiers in Microbiology

VOLUME=7

YEAR=2016

URL=https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2016.00466

DOI=10.3389/fmicb.2016.00466

ISSN=1664-302X

ABSTRACT=<p>Cefquinome is a fourth-generation Cephalosporin approved for use in animals exclusively. The objective of this study was to explore the relationship of cefquinome pharmacokinetic/pharmacodynamic (PK/PD) indices with resistance selection of <italic>Staphylococcus aureus</italic> ATCC25923 in an <italic>in vitro</italic> model. Six dosing regiments of cefquinome at an interval of 24 h for three consecutive times were simulated, resulting in maximum concentrations (C<sub>max</sub>) from 1/2 to 16MIC and terminal half-lives (t<sub>1/2β</sub>) of 3 and 6 h, respectively. The <italic>in vitro</italic> sensitivity of <italic>S. aureus</italic> was monitored by bacterial susceptibility and dynamic time-kill curve experiments over the six cefquinome concentrations. The correlation between changes in bacterial susceptibility (MIC<sub>72</sub>/MIC<sub>0</sub>) and the percentage of time within mutant selection window versus dosing interval (T<sub>MSW</sub> %) was subjected to the Gaussian function and regression analysis. Our results favored the consensus that time above MIC (T &gt; MIC) was recognized as an important PK/PD parameter of cephalosporins for antibacterial efficiency. Cefquinome reached the maximum killing effect when T &gt; MIC% attained approximately 40∼60%. The subsequent correlation analysis demonstrated that resistant <italic>S. aureus</italic> ATCC25923 was easy to occur when T<sub>MSW</sub>% attained an index of about 20% with t<sub>1/2β</sub> of 3 h after multiple dosing, and 40% with t<sub>1/2β</sub> of 6 h after multiple dosing, respectively.</p>