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

作者:Hart S K; Barrett J G*; Brown J A; Papich M G; Powers B E; Sullins K E
来源:Equine Veterinary Journal, 2013, 45(2): 148-153.
DOI:10.1111/j.2042-3306.2012.00633.x

摘要

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%26apos; necks, using 6 replicates with a 3 month washout between experiments. Capillary ultrafiltration probes for collection of interstitial fluid were placed 0cm and 1.5cm from the gel-filled incisions. Samples were collected at 0, 4, 8 and 12 h, and on Days 110. 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%26apos;s signed ranks test. Results: Maximum antimicrobial concentrations were detected at 4h (amikacin), and 8h (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 mu g/ml and 0.63 mu g/ml at 24h and 7 days, respectively. There were no significant differences in histomorphological scores between treatment and control incisions (P0.22). Conclusions and potential relevance: Cross-linked dextran gel is a safe, effective alternative local antimicrobial delivery method.

  • 出版日期2013-3
  • 单位美国弗吉尼亚理工大学(Virginia Tech)