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

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