Accumulation of amikacin in synovial fluid after regional limb perfusion of amikacin sulfate alone and in combination with ticarcillin/clavulanate in horses.
Authors: Zantingh Alanna J, Schwark Wayne S, Fubini Susan L, Watts Ashlee E
Journal: Veterinary surgery : VS
Summary
# Editorial Summary: Amikacin Delivery via Regional Limb Perfusion in Horses Regional limb perfusion (RLP) is a valuable technique for delivering high antibiotic concentrations to equine joints, yet the optimal drug combinations remain incompletely understood. Researchers evaluated whether combining amikacin with ticarcillin/clavulanate during RLP affected synovial fluid drug penetration and antimicrobial efficacy compared to amikacin monotherapy. In standing sedated horses, RLP was performed with amikacin alone (2.5 g) or combined with ticarcillin/clavulanate (2.5 g amikacin plus 7 g ticarcillin/clavulanate), with synovial fluid sampled from the middle carpal joint at 30 and 60 minutes post-tourniquet release. The combination therapy resulted in significantly lower amikacin concentrations in synovial fluid at both timepoints—roughly 75% lower at 30 minutes (4.4 versus 17.5 µg/mL)—and demonstrated reduced antimicrobial activity against both amikacin-susceptible and ticarcillin-resistant *Klebsiella pneumoniae*. This finding suggests potential antagonistic pharmacokinetic interactions between these agents that warrant reconsideration of combined antibiotic regimens during RLP; practitioners may need to adjust dosing protocols or consider sequential rather than concurrent perfusion when treating suspected mixed infections or broad-spectrum coverage.
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Practical Takeaways
- •When performing regional limb perfusion for septic arthritis, amikacin monotherapy achieves superior synovial fluid concentrations compared to combination with ticarcillin/clavulanate, suggesting single-agent protocols may be more effective
- •If broad-spectrum coverage is clinically necessary, consider sequential or separate perfusions rather than combining amikacin with ticarcillin/clavulanate to avoid antagonistic drug interactions
- •This finding challenges common clinical practice of combining aminoglycosides with beta-lactams during RLP and warrants reconsideration of antimicrobial selection protocols
Key Findings
- •Amikacin alone achieved significantly higher synovial fluid concentrations (17.5 µg/mL at 30 min, 15.0 µg/mL at 60 min) compared to amikacin combined with ticarcillin/clavulanate (4.4 µg/mL and 4.6 µg/mL respectively)
- •Combination therapy demonstrated reduced antimicrobial activity against ticarcillin-resistant Klebsiella pneumoniae with smaller zones of inhibition at both 30 and 60 minutes post-tourniquet release
- •Drug interaction between amikacin and ticarcillin/clavulanate during regional limb perfusion resulted in decreased amikacin bioavailability to synovial fluid