Phenotype-Specific Semi-Mechanistic Modelling of Florfenicol Time-Kill Curves in G. parasuis Compared to Other Respiratory Pathogens

Mead, Andrew; Hughes, Abigail; Azzariti, Stefano; Toutain, Pierre-Louis; Pelligand, Ludovic

Abstract

This study examines the pharmacodynamics (PD) of florfenicol (FFN) for treating porcine respiratory diseases by comparing its effects on Glaesserella parasuis, Actinobacillus pleuropneumoniae, and Pasteurella multocida. In vitro time-kill assays and semi-mechanistic PD modeling were used to assess bacterial growth and killing rates at varying FFN concentrations. Species-specific PD models indicated that fAUC/MIC was the best PK/PD index across all species. A. pleuropneumoniae and P. multocida had target values of 1.05 and 1.66 x MIC, respectively for bacteriostasis and 1.12 and 1.87 x MIC for 99.9% kill. Two phenotypes of G. parasuis emerged “fast-kill” and “slow-kill” which displayed distinct bacterial eradication rates despite similar MICs. For "slow-kill" isolates, an average free drug concentration (fAUC/MIC) of 1.46 and 1.63 x MIC (median, range: 1.53-1.69) was required for bacteriostasis and 99.9% kill. "Fast-kill" isolates needed an average free drug concentration of 1.38 x MIC for bacteriostasis and 1.51 x MIC for a 99.9% reduction. Indicating that the rate of kill influences the respective concentration required to achieve an equivalent bacteriological effect. Simulations of clinical dosing predicted bacterial eradication for all species, highlighting the value of phenotype-specific PD modeling in guiding treatment strategies for porcine respiratory infections.

Citation

Mead, A., Hughes, A., Azzariti, S., Toutain, P.-L., & Pelligand, L. (2025). Phenotype-Specific Semi-Mechanistic Modelling of Florfenicol Time-Kill Curves in G. parasuis Compared to Other Respiratory Pathogens. Journal of Veterinary Pharmacology and Therapeutics, https://doi.org/10.1111/jvp.13500

• Journal Article Type: Article
• Acceptance Date: Jan 25, 2025
• Online Publication Date: Feb 7, 2025
• Publication Date: Feb 7, 2025
• Deposit Date: Nov 24, 2024
• Publicly Available Date: Feb 7, 2025
• Print ISSN: 0140-7783
• Electronic ISSN: 1365-2885
• Publisher: American Academy of Veterinary Pharmacology and Therapeutics
• Peer Reviewed: Peer Reviewed
• DOI: https://doi.org/10.1111/jvp.13500