Work

Population pharmacokinetic model–based determination of enrofloxacin susceptibility breakpoints and dosing regimens for Salmonella in chickens

Year: 2026

Type: article

Abstract: 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 (CO WT ) 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 (CO PD ) 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 CO PD was 8 μg/mL. Clinical efficacy studies established a clinical cutoff (CO CL ) 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.

Source: Poultry Science

DOI: 10.1016/j.psj.2026.107767