title: Elution of antimicrobials from a cross-linked dextran gel: In vivo quantification.
abstract: BACKGROUND
  Use of a novel, biodegradable, antimicrobial-impregnated gel provides an alternative method of local treatment of infections in horses.
  
  
  OBJECTIVE
  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
  Cross-linked dextran gel is a safe, effective alternative local antimicrobial delivery method.
authors.affiliation: Marion duPont Scott Equine Medical Center, Virginia-Maryland Regional College of Veterinary Medicine, Virginia Tech, Leesburg, Virginia, USA.
authors.forename: S K
authors.initials: SK
authors.lastname: Hart
authors.forename: J G
authors.initials: JG
authors.lastname: Barrett
authors.forename: J A
authors.initials: JA
authors.lastname: Brown
authors.forename: M G
authors.initials: MG
authors.lastname: Papich
authors.forename: B E
authors.initials: BE
authors.lastname: Powers
authors.forename: K E
authors.initials: KE
authors.lastname: Sullins
mesh_terms: D000583:Amikacin / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D000818:Animals; D000900:Anti-Bacterial Agents / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics*; D019540:Area Under Curve; D002981:Clindamycin / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D003692:Delayed-Action Preparations; D003911:Dextrans / Q000737:chemistry*; D004343:Drug Implants; D006736:Horses / Q000097:blood*; D008826:Microbial Sensitivity Tests; D014640:Vancomycin / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*
chemical_list: D000900:Anti-Bacterial Agents; D003692:Delayed-Action Preparations; D003911:Dextrans; D004343:Drug Implants; D002981:Clindamycin; D014640:Vancomycin; D000583:Amikacin