Determination of the pharmacokinetic-pharmacodynamic cut-off values of marbofloxacin in horses to support the establishment of a clinical breakpoint for antimicrobial susceptibility testing.
Authors: Bousquet-Mélou Alain, Schneider Marc, El Garch Farid, Broussou Diane C, Ferran Aude A, Lallemand Elodie A, Triboulloy Cyrielle, Damborg Peter, Toutain Pierre-Louis
Journal: Equine veterinary journal
Summary
# Editorial Summary: Marbofloxacin Pharmacokinetic-Pharmacodynamic Cut-offs in Horses Marbofloxacin is a critical-use fluoroquinolone antibiotic in equine practice, yet no established clinical breakpoint existed to guide interpretation of susceptibility testing results—a gap that undermines prudent prescribing. Researchers conducted a meta-analysis of five published pharmacokinetic datasets from 131 horses receiving 2 or 10 mg/kg marbofloxacin intravenously, constructing a population model and running 5000 Monte Carlo simulations to determine the pharmacokinetic-pharmacodynamic cut-off (PK/PDCO) values based on the fAUC₂₄/MIC ratio. Using the standard 2 mg/kg dose, the PK/PDCO was established at 0.125 mg/L for Gram-positive pathogens and 0.0625 mg/L for Gram-negative pathogens, with MIC data provided for 54 *Escherichia coli* and 189 *Streptococcus equi* isolates. These cut-offs suggest marbofloxacin is likely efficacious against Enterobacteriaceae infections but unlikely to achieve adequate exposure against *Staphylococcus aureus* and *Streptococcus equi*—findings that should inform clinical selection criteria and potentially shift treatment strategies for respiratory and soft tissue infections in horses. Whilst derived rigorously from population pharmacokinetics, these values lack supporting clinical outcome data and represent a preliminary framework rather than validated clinical breakpoints; further prospective clinical studies are needed to confirm efficacy predictions in field conditions.
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Practical Takeaways
- •Marbofloxacin at 2 mg/kg may be appropriate for treating Gram-negative bacterial infections (e.g., Enterobacteriaceae) in horses but is unlikely to be effective for Gram-positive infections like Streptococcus equi or Staphylococcus aureus
- •Practitioners should request antimicrobial susceptibility testing for marbofloxacin and interpret results using these newly established PK/PD cut-off values to guide clinical decision-making
- •Higher doses or alternative antimicrobials should be considered for confirmed or suspected Gram-positive infections in horses rather than relying on marbofloxacin monotherapy
Key Findings
- •PK/PDCO for marbofloxacin was 0.125 mg/L for Gram-positive pathogens and 0.0625 mg/L for Gram-negative pathogens at 2 mg/kg dose in horses
- •Marbofloxacin is predicted to be efficacious against Enterobacteriaceae infections but unlikely effective against Staphylococcus aureus or Streptococcus equi infections
- •Meta-analysis of 5 published pharmacokinetic datasets in 131 horses generated virtual population of 5000 disposition curves using Monte Carlo simulations
- •Clinical breakpoint establishment requires integration of PK/PD cut-offs with epidemiological data and clinical efficacy information