Effect of Dose on Intra‐Articular Amikacin Sulfate Concentrations Following Intravenous Regional Limb Perfusion in Horses

Abstract

A 3 g amikacin dose is not justified in the majority of distal limb injuries, but should be reserved for isolates with an MIC higher than that achievable with a 2 g dose. Daily IVRLP may be necessary based on our results.

Time to Peak Concentration of Amikacin in the Antebrachiocarpal Joint Following Cephalic Intravenous Regional Limb Perfusion in Standing Horses

“…17,18 Reported MIC of amikacin sulphate of commonly isolated pathogens from musculoskeletal infections ranges between 16 and 64 µg/mL. 20 Although some strains of methicillinresistant Staphylococcus aureus have a reported MIC of 500 µg/mL the median MIC for amikacin sulphate for methicillinresistant-Staphylococcus aureus in one study was reported to be 32 µg/mL. 19 Hence, the recommended C max :MIC ratio of 8:1 was reached in all horses but a 10:1 ratio for the most resistant pathogens (> 64 µg/mL) was only reached in 4/6 horses advocating for a higher dosage in horses suffering from resistant infections.…”

“…19 Hence, the recommended C max :MIC ratio of 8:1 was reached in all horses but a 10:1 ratio for the most resistant pathogens (> 64 µg/mL) was only reached in 4/6 horses advocating for a higher dosage in horses suffering from resistant infections. The reported dosage of amikacin sulphate in IVRLP ranges between 500 mg and 3 g. [6][7][8]10,[12][13][14][15][16]20 We choose to use 2 g in this study based on our clinical experience and previous studies that reached desirable MIC levels of synovial fluid amikacin sulphate with this dose. 6,16 To avoid potential cytotoxicity of amikacin sulphate described after intra-articular administration, the dose could be titrated according to MIC of the cultured pathogens, keeping in mind that bacteriology samples from equine orthopaedic infections frequently yield negative growth.…”

“…This movement does not appear to influence the synovial fluid amikacin sulphate concentration. 8,10,13,15,20,29,33,34 The influence of repeated sampling of synovial fluid on the amikacin sulphate synovial fluid concentration is unknown, not accounted for in previous studies, and should be further investigated. The two horses with suspected perivascular leakage had similar synovial fluid concentrations to the other horses, and the swelling disappeared shortly after tourniquet removal.…”

“…19 A C max :MIC ratio of 8:1-10:1 has been suggested for effective treatment of orthopaedic infections with amikacin sulphate in horses. 13,20 Administration of amikacin sulphate through IVRLP avoids nephrotoxic effects associated with prolonged systemic administration of aminoglycosides in horses, with expected low serum concentrations also after the release of the tourniquet. 16 On the contrary to described positive aspects of a local administration, a recent study concluded that intra-articular administration with as low as 250 mg amikacin sulphate was markedly cytotoxic to joint cells.…”

Equine antimicrobial therapy: Current and past issues facing practitioners

“…Systemic administration is necessary to reach common sites of infection outside of the uterus, and intra‐articular administration, in the case of amikacin, allows for attainment of higher therapeutic concentrations in synovial fluid in the case of a septic joint, as compared to systemic administration. More recently, regional perfusion has proven effective in achieving high local concentrations of amikacin in the distal limb (Harvey et al, 2016; Kelmer et al, 2013; Kilcoyne et al, 2018). Advantages to intra‐articular and regional perfusion include a reduction in required doses as compared to what would be needed if administered systemically to reach these sites, thereby decreasing the potential for adverse effects.…”