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

Equine Vet J. 2013 Mar;45(2):148-53. doi: 10.1111/j.2042-3306.2012.00633.x. Epub 2012 Sep 26.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amikacin / administration & dosage
  • Amikacin / blood
  • Amikacin / pharmacokinetics*
  • Animals
  • Anti-Bacterial Agents / blood
  • Anti-Bacterial Agents / chemistry
  • Anti-Bacterial Agents / pharmacokinetics*
  • Area Under Curve
  • Clindamycin / administration & dosage
  • Clindamycin / blood
  • Clindamycin / pharmacokinetics*
  • Delayed-Action Preparations
  • Dextrans / chemistry*
  • Drug Implants
  • Horses / blood*
  • Microbial Sensitivity Tests
  • Vancomycin / administration & dosage
  • Vancomycin / blood
  • Vancomycin / pharmacokinetics*

Substances

  • Anti-Bacterial Agents
  • Delayed-Action Preparations
  • Dextrans
  • Drug Implants
  • Clindamycin
  • Vancomycin
  • Amikacin