Elution of antimicrobials from a cross-linked dextran gel: In vivo Quantification

Authors

  • S. K. HART,

    1. Dept. Clinical Studies, New Bolton Center, Kennett Square, Pennsylvania, USA
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  • J. G. BARRETT,

    Corresponding author
    1. Marion duPont Scott Equine Medical Center, Virginia-Maryland Regional College of Veterinary Medicine, Virginia Tech, Leesburg, Virginia, USA
      email: jgbarrett@vt.edu
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  • J. A. BROWN,

    1. Marion duPont Scott Equine Medical Center, Virginia-Maryland Regional College of Veterinary Medicine, Virginia Tech, Leesburg, Virginia, USA
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  • M. G. PAPICH,

    1. Department of Molecular Biomedical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, North Carolina, USA
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  • B. E. POWERS,

    1. Director, Veterinary Diagnostic Laboratory, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, Colorado, USA
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  • K. E. SULLINS

    1. Marion duPont Scott Equine Medical Center, Virginia-Maryland Regional College of Veterinary Medicine, Virginia Tech, Leesburg, Virginia, USA
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  • Presented in part at American College of Veterinary Surgeons Symposium 2009, Washington DC

email: jgbarrett@vt.edu

Summary

Reasons for performing study: Use of a novel, biodegradable, antimicrobial-impregnated gel provides an alternative method of local treatment of infections in horses.

Objectives: To determine in vivo elution of antimicrobial medications from antimicrobial-impregnated cross-linked dextran gel and to evaluate the effect on wound healing when implanted subcutaneously in horses.

Methods: Amikacin-, vancomycin- or amikacin/clindamycin-impregnated gel was placed subcutaneously in 11 horses' necks, using 6 replicates with a 3 month washout between experiments. Capillary ultrafiltration probes for collection of interstitial fluid were placed 0 cm and 1.5 cm from the gel-filled incisions. Samples were collected at 0, 4, 8 and 12 h, and on Days 1–10. Blood was collected on Days 0, 1 and 7. Amikacin and vancomycin samples were analysed via fluorescence polarisation immunoassay, and clindamycin samples via high-performance liquid chromatography. Histology of biopsy samples was performed at the completion of the study. Differences in mean histomorphological scores between groups were assessed using Wilcoxon's signed ranks test.

Results: Maximum antimicrobial concentrations were detected at 4 h (amikacin), and 8 h (vancomycin, and amikacin and clindamycin from the combination gel). Mean ± s.d. peak concentrations for amikacin, vancomycin, amikacin (amikacin/clindamycin) and clindamycin were 6133 ± 1461, 7286 ± 2769, 3948 ± 317 and 985 ± 960, respectively. Median number of days for which antimicrobial concentration remained above minimum inhibitory concentration for target microorganisms at implantation was ≥10 days for vancomycin, 9 days (± 1) for amikacin and 8 days (± 1) for clindamycin. Mean plasma amikacin and vancomycin concentrations were lower than detectable limits; mean serum clindamycin concentrations were 0.52 µg/ml and 0.63 µg/ml at 24 h and 7 days, respectively. There were no significant differences in histomorphological scores between treatment and control incisions (P≥0.22).

Conclusions and potential relevance: Cross-linked dextran gel is a safe, effective alternative local antimicrobial delivery method.

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