Rational dosage regimens for cephalothin and cefazolin using pharmacokinetics and pharmacodynamics analysis in healthy horses.
Authors: Kuroda Taisuke, Minamijima Yohei, Niwa Hidekazu, Tamura Norihisa, Mita Hiroshi, Fukuda Kentaro, Kaimachi Masahiro, Suzuki Yuto, Enoki Yuki, Taguchi Kazuaki, Matsumoto Kazuaki, Toutain Pierre-Louis, Bousquet-Melou Alain, Kasashima Yoshinori
Journal: Equine veterinary journal
Summary
# Editorial Summary: Optimising First-Generation Cephalosporin Dosing in Horses First-generation cephalosporins remain cornerstone antimicrobials in equine practice, yet evidence-based dosage recommendations have been limited by sparse pharmacokinetic and pharmacodynamic (PK/PD) data specific to horses. Kuroda and colleagues addressed this gap by measuring plasma concentrations of cephalothin and cefazolin following single intravenous doses (22 mg/kg and 10 mg/kg respectively) in healthy horses, then integrating these data with pathogen susceptibility profiles and Monte Carlo simulations to determine optimal dosing intervals. Both drugs showed low serum protein binding (cephalothin 19.9%, cefazolin 15.2%), with MIC₉₀ values of 0.12 mg/L against *Streptococcus zooepidemicus* and 0.5 mg/L against *Staphylococcus aureus*. To achieve 90% probability of target attainment using a PK/PD breakpoint of free drug concentration exceeding the MIC₉₀ for 40% of the dosing interval, cephalothin required more frequent dosing than currently standard—every 4 hours for *S. aureus* infections—whilst cefazolin proved effective at wider intervals than typically recommended (every 12 hours for *S. zooepidemicus*, every 8 hours for *S. aureus*). These findings suggest that practitioners may be underdosing cephalothin for staphylococcal infections whilst potentially overdosing cefazolin, particularly for streptococcal conditions, warranting reconsideration of current empirical protocols in clinical practice.
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Practical Takeaways
- •Cephalothin dosing for Staph. aureus infections needs more frequent administration (every 4 hours) than currently recommended to effectively control infection
- •Cefazolin can be dosed less frequently than current protocols suggest—q12h for Strep. zooepidemicus and q8h for Staph. aureus—simplifying treatment regimens
- •These PK/PD-optimized dosages improve efficacy while potentially reducing treatment burden and cost in equine practice
Key Findings
- •Cephalothin protein binding was 19.9% ± 8.4% and cefazolin binding was 15.2% ± 8.5% in equine serum
- •MIC90 for both drugs against S. zooepidemicus was 0.12 mg/L and against S. aureus was 0.5 mg/L
- •Cephalothin requires 22 mg/kg q8h for S. zooepidemicus and q4h for S. aureus to achieve 90% PTA
- •Cefazolin requires 10 mg/kg q12h for S. zooepidemicus and q8h for S. aureus to achieve 90% PTA