Pharmacokinetic and pharmacodynamic modeling of cyadox against Clostridium perfringens in swine

Abstract

Abstract The purpose of this study was to evaluate the activity of cyadox against Clostridium perfringens in swine and optimize the dosage regimen using ex vivo pharmacokinetic-pharmacodynamic (PK-PD) modeling. After oral administration, the ileum fluid of pigs containing the free cyadox was collected by implanted ultrafiltration probes. The Tmax, AUC24h, and CL/F of free cyadox in the ileum fluid were 1.96 h, 106.40 μg/h/mL, and 0.27 L/kg/h, respectively. Cyadox displayed a concentration-dependent killing action against C. perfrignens. The minimum inhibitory concentration (MIC) of cyadox against 60 clinical isolates ranged from 0.5 to 8 μg/mL, with MIC50 and MIC90 values of 2 and 4 μg/mL, respectively. The MIC was 2 μg/mL against the pathogenic C. perfrignens isolate CPFK122995 in both broth and ileum fluid. According to the inhibitory sigmoid Emax modeling, the AUC24h/MIC ratios of ileum fluid required to achieve the bacteriostatic, bactericidal, and virtual bacterial elimination effects were 26.72, 39.54, and 50.69 h, respectively. Monte Carlo simulations for the 90% target attainment rate (TAR) predicted daily doses of 29.30, 42.56, and 54.50 mg/kg over 24 h to achieve bacteriostatic, bactericidal, and elimination actions, respectively. The results of this study suggest that cyadox is a promising antibacterial agent for the treatment of C. perfringens infections, and can be used to inform its clinical use.