Elution of antimicrobials from a cross-linked dextran gel: In vivo quantification.
Abstract: 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.
© 2012 EVJ Ltd.
Publication Date: 2012-09-26 PubMed ID: 23009285DOI: 10.1111/j.2042-3306.2012.00633.xGoogle Scholar: Lookup
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- Journal Article
- Research Support
- Non-U.S. Gov't
Summary
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The research investigates a new method of delivering antimicrobial medication to horses using a biodegradable gel. The study aimed to determine how antimicrobial medications were released from the gel once implanted under the skin of a horse and to understand its effects on wound healing.
Research Methodology
- The study involved the placing of antimicrobial-impregnated cross-linked dextran gel under the skin in the necks of 11 horses. The study used three types of antimicrobial medications – amikacin, vancomycin and a combination of amikacin/clindamycin.
- A total of 6 replicates were performed on each horse with a resting period of 3 months between experiments.
- Small probes were inserted at different points around the incision, where the gel-antimicrobial medication was placed. These probes identified the amount of antimicrobial medication in the interstitial fluid of the wounds over a period of 10 days.
- Blood was drawn from all 11 horses on the day of the operation and then again on the first and seventh day post-operation.
- The concentration of the used antimicrobials was ascertained using fluorescence polarisation immunoassay for amikacin and vancomycin, and high-performance liquid chromatography for clindamycin.
- At the end of the study, a biopsy was performed on the incisions to understand the effect of the antimicrobial medication and the dextran gel on wound healing.
Findings
- Maximum concentration of amikacin was detected 4 hours after administration and for vancomycin and the combination gel, it was 8 hours.
- The amount of antimicrobial medication that remains over the minimum inhibitory concentration (MIC) for the targeted microorganism lasted for up to 10 days for vancomycin, 9 days for amikacin, and 8 days for clindamycin post-implantation.
- Concentrations of amikacin and vancomycin in the bloodstream were too low to be detected, whereas the concentrations of clindamycin were 0.52 µg/ml at 24 hours and 0.63 µg/ml at 7 days.
- There was no significant difference in wound healing between the treatment and control incisions, indicating that the use of the gel and antimicrobial medication did not affect wound healing negatively.
Conclusion
The research concludes that the antimicrobial-impregnated cross-linked dextran gel is a safe and effective localized delivery method for antimicrobial medication in the treatment of infection in horses.
Cite This Article
APA
Hart SK, Barrett JG, Brown JA, Papich MG, Powers BE, Sullins KE.
(2012).
Elution of antimicrobials from a cross-linked dextran gel: In vivo quantification.
Equine Vet J, 45(2), 148-153.
https://doi.org/10.1111/j.2042-3306.2012.00633.x Publication
Researcher Affiliations
- Marion duPont Scott Equine Medical Center, Virginia-Maryland Regional College of Veterinary Medicine, Virginia Tech, Leesburg, Virginia, USA.
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
Citations
This article has been cited 3 times.- Peng ZH, Dickerson VM, Fajt VR, Gould EN, Droog M, Thieman Mankin KM. Serum amikacin concentrations in dogs with naturally occurring open wounds treated with topical amikacin in carboxymethylcellulose hydrogel. Vet Surg 2025 Apr;54(3):453-460.
- Ribeiro G, Carvalho L, Borges J, Prazeres J. The Best Protocol to Treat Equine Skin Wounds by Second Intention Healing: A Scoping Review of the Literature. Animals (Basel) 2024 May 18;14(10).
- Reed TP, Thomas LA, Weeren FR, Ruth JD, Anders BB. A novel dextran polymer hydrogel local antimicrobial therapy in dogs: A pilot study. Can Vet J 2016 Feb;57(2):189-95.
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