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

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 × MIC, respectively for bacteriostasis and 1.12 and 1.87 × 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 × 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 × MIC for bacteriostasis and 1.51 × MIC for a 99.9% reduction. Indicating that the rate of kill influences the respective average free concentration required to achieve an equivalent antibacterial effect. Simulations of clinical dosing of FFN predicted bacterial eradication for all species, highlighting the value of phenotype-specific PD modeling in guiding treatment strategies for porcine respiratory infections.