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

Xia Xiao,Rui-Juan Huang,Yu-Feng Zhou,Ya-Hong Liu,Jian Sun,Guilin Gary Qiao,Ting Huang,Yi Chen

doi:10.1186/s12917-015-0343-7

Abstract

BackgroundHaemophilus 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.ResultsA 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 MIC50 and MIC90 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-log10-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.ConclusionsThe 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.

Highlights

Haemophilus parasuis (H. parasuis) causes Glässer’s disease and multisystem infectious disease
EC50 is the T% > Minimal inhibitory concentrations (MIC) value producing a 50% reduction in bacterial counts from the initial inoculum, and N is the Hill coefficient that describes the steepness of the T% > MIC–effect curve
A low peak of MIC was observed at 8 mg/L, the MICs distributed in a normal distribution pattern basically with a definite peak at 0.25 mg/L

Summary

Introduction

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. The European Medicines Agency (EMA) proposes CEQ for the treatment of pigs against respiratory tract infections with a dosage regimen of 2 mg/kg/24 h bodyweight (BW) for three to five days [14]. As one of the major pathogens of respiratory tract of pigs, few studies have investigated the killing pattern and PK/PD characteristics of this drug against H. parasuis, the Clinical and Laboratory Standards Institute (CLSI) subcommittee on Veterinary Antimicrobial Susceptibility Testing (VAST) which establishes veterinary clinically breakpoints [15] has not established breakpoints for H. parasuis. The value of PK/PD surrogate which is of great utility in CEQ clinical usage and the CEQ PK/PD cutoff providing fundamental data for CEQ breakpoint determination should be illuminated

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Conclusion