Population pharmacokinetic model–based determination of enrofloxacin susceptibility breakpoints and dosing regimens for Salmonella in chickens
4 affiliations
- 1Department of Veterinary Medicine Science, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, Hubei, 430070, China
- 2National Reference Laboratory of Veterinary Drug Residues (HZAU), Wuhan, Hubei, 430070, China
- 3MOA Key Laboratory for Detection of Veterinary Drug Residues, Wuhan, Hubei, 430070, China
- 4MOA Laboratory of Risk Assessment for Quality and Safety of Livestock and Poultry Products, Wuhan, Hubei, 430070, China
Abstract
Salmonella is a major zoonotic pathogen and poses significant threats to animal production and public health. Enrofloxacin is widely used to treat gastrointestinal infections in chickens because of its favorable pharmacokinetic and pharmacodynamic properties. However, the increasing prevalence of reduced susceptibility to enrofloxacin has become a growing concern. This study aimed to establish susceptibility breakpoints for enrofloxacin against chicken–origin Salmonella and to optimize the corresponding dosing regimen. Minimum inhibitory concentrations of enrofloxacin were determined for 187 Salmonella isolates following CLSI guidelines, and the epidemiological cutoff (COWT) was established at 4 μg/mL. A population pharmacokinetic model was developed using literature–derived data, and Monte Carlo simulations were performed to estimate the pharmacodynamic targets. The plasma–based pharmacodynamic cutoff (COPD) was determined to be 0.125 μg/mL via POP–PK modeling and 0.25 μg/mL via Monte Carlo simulation, while the cecal content–based COPD was 8 μg/mL. Clinical efficacy studies established a clinical cutoff (COCL) of 1 μg/mL. On the basis of these results, the final susceptibility breakpoints for enrofloxacin against chicken–origin Salmonella were determined to be 4 μg/mL for plasma and 1 μg/mL for cecal contents. An optimized dosing regimen of 4.25 – 4.77 mg/kg body weight administered orally twice daily for three consecutive days is recommended to achieve effective bacterial clearance while minimizing resistance development. In conclusion, this study provides the first comprehensive set of enrofloxacin breakpoints specifically for chicken‑origin Salmonella in China, integrating microbiological, PK‑PD, and clinical data. The proposed breakpoints and dosing regimen offer a practical tool for resistance surveillance, guide evidence‑based antimicrobial use in poultry, and serve as a methodological reference for establishing national veterinary breakpoints, thereby supporting global efforts to combat antimicrobial resistance.
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BibTeX
@article{sun2026population,
title = {{Population pharmacokinetic model–based determination of enrofloxacin susceptibility breakpoints and dosing regimens for Salmonella in chickens}},
author = {Lei Sun and Cheng Yang Zhang and Meixia Huo and Hanyu Wang and Yuanhu Pan and Yanfei Tao and Lingli Huang},
journal = {Poultry Science},
year = {2026},
month = sep,
doi = {10.1016/j.psj.2026.107767},
url = {https://doi.org/10.1016/j.psj.2026.107767},
note = {CC BY-NC-ND 4.0},
}
RIS
TY - JOUR
TI - Population pharmacokinetic model–based determination of enrofloxacin susceptibility breakpoints and dosing regimens for Salmonella in chickens
AU - Lei Sun
AU - Cheng Yang Zhang
AU - Meixia Huo
AU - Hanyu Wang
AU - Yuanhu Pan
AU - Yanfei Tao
AU - Lingli Huang
PY - 2026
DA - 2026/09/24
JO - Poultry Science
DO - 10.1016/j.psj.2026.107767
UR - https://doi.org/10.1016/j.psj.2026.107767
AB - Salmonella is a major zoonotic pathogen and poses significant threats to animal production and public health. Enrofloxacin is widely used to treat gastrointestinal infections in chickens because of its favorable pharmacokinetic and pharmacodynamic properties. However, the increasing prevalence of reduced susceptibility to enrofloxacin has become a growing concern. This study aimed to establish susceptibility breakpoints for enrofloxacin against chicken–origin Salmonella and to optimize the corresponding dosing regimen. Minimum inhibitory concentrations of enrofloxacin were determined for 187 Salmonella isolates following CLSI guidelines, and the epidemiological cutoff (COWT) was established at 4 μg/mL. A population pharmacokinetic model was developed using literature–derived data, and Monte Carlo simulations were performed to estimate the pharmacodynamic targets. The plasma–based pharmacodynamic cutoff (COPD) was determined to be 0.125 μg/mL via POP–PK modeling and 0.25 μg/mL via Monte Carlo simulation, while the cecal content–based COPD was 8 μg/mL. Clinical efficacy studies established a clinical cutoff (COCL) of 1 μg/mL. On the basis of these results, the final susceptibility breakpoints for enrofloxacin against chicken–origin Salmonella were determined to be 4 μg/mL for plasma and 1 μg/mL for cecal contents. An optimized dosing regimen of 4.25 – 4.77 mg/kg body weight administered orally twice daily for three consecutive days is recommended to achieve effective bacterial clearance while minimizing resistance development. In conclusion, this study provides the first comprehensive set of enrofloxacin breakpoints specifically for chicken‑origin Salmonella in China, integrating microbiological, PK‑PD, and clinical data. The proposed breakpoints and dosing regimen offer a practical tool for resistance surveillance, guide evidence‑based antimicrobial use in poultry, and serve as a methodological reference for establishing national veterinary breakpoints, thereby supporting global efforts to combat antimicrobial resistance.
SN - 0032-5791
SN - 1525-3171
ER -