Pharmacokinetics of ceftazidime after regional limb perfusion in standing horses.
Authors: Oreff Gil L, Tatz Amos J, Dahan Roee, Segev Gilad, Haberman Shelley, Britzi Malka, Kelmer Gal
Journal: Veterinary surgery : VS
Summary
# Ceftazidime Regional Limb Perfusion in Horses: Pharmacokinetics and Clinical Limitations Regional limb perfusion (RLP) offers the potential to achieve high antibiotic concentrations in equine distal limb joints whilst minimising systemic exposure, but the suitability of any agent depends on maintaining therapeutic concentrations for an adequate duration. Gil and colleagues investigated whether ceftazidime—a third-generation cephalosporin with activity against resistant gram-negative organisms—could reliably achieve this goal when administered via RLP in standing, sedated horses. Following injection of 2 g ceftazidime into the cephalic vein of eight healthy horses, the researchers measured drug concentrations in synovial fluid from the metacarpophalangeal joint over a 24-hour period using liquid chromatography, allowing calculation of pharmacokinetic parameters including peak concentration (Cmax), half-life and the area under the curve. Whilst initial synovial concentrations reached an impressive 235 µg/mL—approximately 15 times the minimal inhibitory concentration for most orthopedic pathogens including Pseudomonas aeruginosa—this advantage proved transient; by 6 hours post-perfusion, only one horse maintained concentrations above the MIC, rendering once-daily dosing impractical for sustained antimicrobial effect. These findings suggest that although RLP generates exceptional early joint penetration with ceftazidime, the rapid decline in synovial concentrations makes this protocol unsuitable for routine clinical use and highlight the need for either more frequent dosing intervals or alternative agents with superior synovial half-lives.
Read the full abstract on PubMed
Practical Takeaways
- •Regional limb perfusion with ceftazidime achieves very high initial joint fluid concentrations but cannot sustain therapeutic levels with once-daily dosing
- •This dosing protocol should not be used clinically for equine joint infections without modification (likely requiring more frequent dosing intervals)
- •Alternative antimicrobial strategies or modified perfusion protocols should be considered for treating distal limb orthopedic infections in horses
Key Findings
- •Ceftazidime achieved maximum synovial fluid concentration of 235 µg/mL, which is 15 times higher than the MIC for most bacteria including Pseudomonas aeruginosa (MIC = 16 µg/mL)
- •Synovial concentrations declined rapidly, remaining above MIC in only 1 of 8 horses by 6 hours post-perfusion
- •Single daily regional limb perfusion with 2 g ceftazidime cannot maintain therapeutic concentrations in synovial fluid for adequate antimicrobial coverage