The purpose of this study was to evaluate the activity of cyadox against Clostridium perfringens in\nswine and optimize the dosage regimen using ex vivo pharmacokinetic-pharmacodynamic (PK-PD)\nmodeling. After oral administration, the ileum fluid of pigs containing the free cyadox was collected\nby implanted ultrafiltration probes. The Tmax, AUC24h, and CL/F of free cyadox in the ileum fluid were\n1.96 h, 106.40 �¼g/h/mL, and 0.27 L/kg/h, respectively. Cyadox displayed a concentration-dependent\nkilling action against C. perfrignens. The minimum inhibitory concentration (MIC) of cyadox against 60\nclinical isolates ranged from 0.5 to 8 �¼g/mL, with MIC50 and MIC90 values of 2 and 4 �¼g/mL, respectively.\nThe MIC was 2 �¼g/mL against the pathogenic C. perfrignens isolate CPFK122995 in both broth and ileum\nfluid. According to the inhibitory sigmoid Emax modeling, the AUC24h/MIC ratios of ileum fluid required to\nachieve the bacteriostatic, bactericidal, and virtual bacterial elimination effects were 26.72, 39.54, and\n50.69 h, respectively. Monte Carlo simulations for the 90% target attainment rate (TAR) predicted daily\ndoses of 29.30, 42.56, and 54.50 mg/kg over 24 h to achieve bacteriostatic, bactericidal, and elimination\nactions, respectively. The results of this study suggest that cyadox is a promising antibacterial agent for\nthe treatment of C. perfringens infections, and can be used to inform its clinical use.
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