Florfenicol sustained-release formulation does not promote resistance emergence in non-target bacteria: hollow-fibre infection studies with pig pathogens and commensals.

Abstract

Aims: This study assessed the pharmacodynamic (PD) efficacy and resistance selection risk of a novel sustained-release (SR) florfenicol formulation versus a conventional two-dose regimen for treating swine respiratory pathogens, with particular attention to potential impacts on non-target bacteria.

Methods and results: Using a hollow-fibre infection model, simulated plasma pharmacokinetics for SR (30 mg kg-1, single dose) and conventional (2 × 15 mg kg-1, 48 h apart) formulations were emulated. Bactericidal efficacy was quantified against Actinobacillus pleuropneumoniae, Pasteurella multocida, and G. parasuis, while Escherichia coli was included to assess resistance emergence. Both formulations achieved rapid bacterial eradication in target pathogens with no regrowth. PD indices (fAUC/MIC, %fT > MIC) demonstrated comparable or superior exposures for the SR formulation. Median %fT within the mutant selection window (%fTMSW) was low across treatments: 2.9%-3.5% for A. pleuropneumoniae, 12.7%-15.7% for P. multocida, and 0% for E. coli. No resistant E. coli mutants emerged, one transient less-susceptible subpopulation (<0.0001%) with a 2-fold MIC increase (still below ECOFF) was transiently observed, and florfenicol concentrations remained below MIC and mutant prevention concentration thresholds.

Conclusions: The SR formulation of florfenicol showed equivalent efficacy to conventional dosing against key swine respiratory pathogens and posed minimal risk for selecting resistance in non-target E. coli. This supports the SR formulation as an effective single-dose alternative in veterinary practice.