Elution of antimicrobials from a cross‐linked dextran gel:In vivoQuantification

Abstract

Use of a novel, biodegradable, antimicrobial-impregnated gel provides an alternative method of local treatment of infections in horses. 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. 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. 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). Cross-linked dextran gel is a safe, effective alternative local antimicrobial delivery method.