In vitro dynamic pharmacokinetic/pharmacodynamic(PK/PD) modeling and PK/PD cutoff of cefquinome against Haemophilus parasuis

BACKGROUND Haemophilus parasuis (H. parasuis) causes Glässer's disease and multisystem infectious disease. It is one of the major causes of nursery mortality in swine herds. Cefquinome (CEQ) is proposed for the treatment of pigs against respiratory tract infection. However, few studies have investigated the PK/PD characteristics and PK/PD cutoff of this drug against H. parasuis. RESULTS A total of 213 H. parasuis strains were isolated from diseased pigs in China. The minimal inhibitory concentrations (MICs) of CEQ against these isolates were determined. The MIC(50) and MIC(90) values were 0.125 and 8 mg/L, respectively. An in vitro dynamic PK/PD infection model was used to investigate the antimicrobial effect of CEQ against H. parasuis strain of serotype 5. The target values of CEQ for 3-log(10)-unit and 4-log10-unit decreases effects were the percent time that CEQ concentrations were above the minimum inhibitory concentration (T% > MIC) of 61 and 71 respectively. According to Monte Carlo simulation, the PK/PD cutoff for CEQ against H. parasuis was 0.06 mg/L. The suggested dose regimen was 4 mg/kg/12 h BW. CONCLUSIONS The value of PK/PD surrogate marker T% > MIC is of great utility in CEQ clinical usage. The very first CEQ PK/PD cutoff provide fundamental data for CEQ breakpoint determination. A more desirable dose regimen against H. parasuis was provided for CEQ using in China district.