Determination of Susceptibility Breakpoint for Cefquinome against Streptococcus suis in Pigs

Abstract

Streptococcus suis (S. suis), a zoonotic pathogen, causes severe diseases in both pigs and human beings. Cefquinome can display excellent antibacterial activity against gram-negative and gram-positive bacteria. The aim of this study was to derive an optimal dosage of cefquinome against S. suis with a pharmacokinetic/pharmacodynamic (PK/PD) integration model in the target infection site and to investigate the cutoffs monitoring the changes of resistance. The minimum inhibitory concentration (MIC) distribution of cefquinome against 342 S. suis strains was determined. MIC50 and MIC90 were 0.06 and 0.25 μg/mL, respectively. The wild-type cutoff was calculated as 1 μg/mL. A two-compartmental model was applied to calculate the main pharmacokinetic parameters after 2 mg/kg cefquinome administered intramuscularly. An optimized dosage regimen of 3.08 mg/kg for 2-log10 CFU reduction was proposed by ex vivo PK/PD model of infected swine. The pharmacokinetic-pharmacodynamic cutoff was calculated as 0.06 μg/mL based on PK/PD targets. Based on the clinical effectiveness study of pathogenic MIC isolates, the clinical cutoff was calculated as 0.5 μg/mL. A clinical breakpoint was proposed as 1 μg/mL. In conclusion, the results offer a reference for determining susceptibility breakpoint of cefquinome against S. suis and avoiding resistance emergence by following the optimal dosage regimen.