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

Fang Wang; Kun Mi; Ijaz Ahmad; Shuyu Xie; Hafiz Iftikhar Hussain; Zonghui Yuan; Menghong Dai; Lingli Huang

doi:10.1016/j.micpath.2020.103981

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

Microb Pathog. 2020 Apr:141:103981. doi: 10.1016/j.micpath.2020.103981. Epub 2020 Jan 18.

Authors

Fang Wang¹, Kun Mi¹, Ijaz Ahmad², Shuyu Xie¹, Hafiz Iftikhar Hussain¹, Zonghui Yuan³, Menghong Dai⁴, Lingli Huang⁵

Affiliations

¹ National Reference Laboratory of Veterinary Drug Residues (HZAU), Huazhong Agricultural University, Wuhan, China; MAO Key Laboratory for Detection of Veterinary Drug Residues, Huazhong Agricultural University, Wuhan, China.
² Department of Animal Health, University of Agriculture Peshawar, 25130, Pakistan.
³ National Reference Laboratory of Veterinary Drug Residues (HZAU), Huazhong Agricultural University, Wuhan, China; MAO Key Laboratory for Detection of Veterinary Drug Residues, Huazhong Agricultural University, Wuhan, China; MOA Laboratory for Risk Assessment of Quality and Safety of Livestock and Poultry Products, Huazhong Agricultural University, Wuhan, China.
⁴ National Reference Laboratory of Veterinary Drug Residues (HZAU), Huazhong Agricultural University, Wuhan, China; MAO Key Laboratory for Detection of Veterinary Drug Residues, Huazhong Agricultural University, Wuhan, China. Electronic address: daimenghong@mail.hzau.edu.cn.
⁵ MAO Key Laboratory for Detection of Veterinary Drug Residues, Huazhong Agricultural University, Wuhan, China; MOA Laboratory for Risk Assessment of Quality and Safety of Livestock and Poultry Products, Huazhong Agricultural University, Wuhan, China. Electronic address: huanglingli@mail.hzau.edu.cn.

PMID: 31962185
DOI: 10.1016/j.micpath.2020.103981

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 (C_max), maximum concentration time (T_max), 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 AUC_24h/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.

Keywords: Broiler; Clostridium perfringens; Cyadox; Dosage regimen; PK/PD modeling.

MeSH terms

Administration, Oral
Animals
Anti-Bacterial Agents / administration & dosage
Anti-Bacterial Agents / pharmacokinetics
Anti-Bacterial Agents / pharmacology*
Chromatography, High Pressure Liquid
Clostridium Infections / veterinary*
Clostridium perfringens / drug effects*
Disease Models, Animal
Dose-Response Relationship, Drug
Drug Monitoring
Mice
Microbial Sensitivity Tests
Quinoxalines / administration & dosage
Quinoxalines / pharmacokinetics
Quinoxalines / pharmacology
Swine
Swine Diseases / drug therapy*
Swine Diseases / microbiology*

Substances

Anti-Bacterial Agents
Quinoxalines
cyadox