Antibacterial activity of cyadox against Clostridium perfringens in broilers and a dosage regimen design based on pharmacokinetic-pharmacodynamic modeling

Abstract

Necrotic enteritis is an intestinal disease caused by Clostridium perfringens (C. perfringens) that results in high economic losses to the poultry industry. The purpose of this study was to investigate the antibacterial activity of cyadox against C. perfringens and to formulate its dosage regimen based on pharmacokinetics/pharmacodynamics (PK/PD) modeling in broilers. The PK parameters of cyadox in ileum of healthy and infected broilers following oral administration at 30 mg/kg body weight (BW) were investigated and PD study the MIC, MBC, MPC, and PAE were determined. The time-killing curves were established in vitro and ex vivo to evaluate the antibacterial activity of cyadox against C. perfringens. The results revealed that the MIC of cyadox against C. perfringens was 1–16 μg/mL. After oral administration of cyadox, the peak concentration (Cmax), maximum concentration time (Tmax), and area under the concentration-time curve (AUC) in ileum content of broilers were 143.55–161.48 μg/mL, 1.08–1.25 h, and 359.51–405.69 μg h/mL respectively. After Integrating the in vivo PK and ex vivo PD data the AUC24h/MIC values needed for bacteriostatic, bactericidal and bacterial eradication were 27.71 h, 78.93 h, and 165.14 h, respectively. By model validation, the cure rate was 85.71%. In conclusion, a dosage regimen of 14.02 mg/kg repeated after every 12 h for 3–5days was expected to be therapeutically effective in broilers against C. perfringens with MIC ≤2 μg/mL.