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Equine veterinary journal2016; 49(3); 341-344; doi: 10.1111/evj.12614

Plasma, subcutaneous tissue and bone concentrations of ceftiofur sodium after regional limb perfusion in horses.

Abstract: Regional limb perfusion (RLP) is an effective treatment option for injuries and infections of the distal limb in horses. Using ceftiofur sodium in RLP has been studied due to its superior spectrum of Gram-positive organisms compared to aminoglycosides, but it is not known if this antimicrobial drug adequately penetrates subcutaneous tissue and bone. Objective: To determine the concentration of ceftiofur in plasma, subcutaneous tissue and bone in horses after RLP. Methods: Experimental prospective study. Methods: Six healthy horses were used in this study. Under standing sedation, an Esmarch tourniquet was applied to both proximal metacarpi and RLP was performed in each forelimb by injecting either ceftiofur sodium (experimental limb) or saline (control limb) i.v. in the lateral palmar digital vein. The experimental limb was injected with 2 g ceftiofur diluted to 60 mL with sterile saline. The control limb was injected with 60 mL of sterile saline. The tourniquet was left in place for 30 min post injection. Plasma, subcutaneous tissue and cortical bone samples were collected immediately after tourniquet removal (0.5 h), 12 and 24 h post injection. Ceftiofur concentrations and its active metabolite desfuroylceftiofur were analysed using high performance liquid chromatography-tandem mass spectrometry and the results were compared between control and experimental limbs using a Wilcoxon signed rank test. Results: The median plasma concentrations were greater than the minimum inhibitory concentration (MIC) for common pathogens (1 μg/mL) at 0 and 12 h post RLP. The median subcutaneous tissue concentrations were greater than MIC (1 μg/g) at all 3 time points in the experimental limb. The median bone concentration was above MIC (1 μg/g) at time 0 in the experimental limb but was below MIC at 12 and 24 h in the experimental limb. Conclusions: Ceftiofur administration via RLP maintained plasma concentrations above MIC for 12 h. Subcutaneous tissue concentrations above MIC were maintained for 24 h. Bone concentrations were only above MIC immediately after tourniquet removal. Further research is needed to evaluate ceftiofur administration via RLP and its implications in disease states.
Publication Date: 2016-08-24 PubMed ID: 27458113DOI: 10.1111/evj.12614Google Scholar: Lookup
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  • Clinical Trial
  • Journal Article

Summary

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This research examines how well an antibiotic drug, ceftiofur sodium, penetrates into the tissue and bone of horses’ limbs after treatment via Regional Limb Perfusion (RLP), a specialized local delivery method of medication.

Research Objective

The main objective of this study was to determine the concentrations of ceftiofur in the plasma, subcutaneous tissue (beneath the skin), and cortical bone in horses after undergoing RLP. The study attempted to understand whether the antibiotic adequately penetrates these three areas in order to effectively treat distal limb injuries and infections.

Methods Used

  • Six healthy horses acted as the subjects of the study.
  • A technique called Esmarch tourniquet was applied to each horse’s forelimbs under mild sedation.
  • Each limb was injected with either ceftiofur sodium or saline, designated as the experimental or control limb respectively.
  • The tourniquet ensured that the injected substance was concentrated in the limb for enhanced penetration and was removed 30 minutes after the injection.
  • At 0.5, 12, and 24 hours post-injection, plasma, subcutaneous tissue, and cortical bone samples were collected from each horse.
  • The samples were then tested to determine the concentrations of ceftiofur and its active metabolite, desfuroylceftiofur, using High Performance Liquid Chromatography-Tandem Mass Spectrometry (HPLC-MS).
  • Finally, the concentration results from the experimental (ceftiofur-injected) limbs were compared to those from the control (saline-injected) limbs.

Results Analysis

  • In both plasma and subcutaneous tissues, the concentration of ceftiofur retained was found to be above the minimum required to inhibit pathogen growth at first two time intervals examined.
  • However, in the bone, this concentration was only found right after the tourniquet removal and not in subsequent time intervals.
  • Therefore, while ceftiofur was successfully maintained in the plasma for up to 12 hours and in the subcutaneous tissue for 24 hours, its concentration in the bone was only satisfactory immediately after injection.

Conclusions and Further Research

While ceftiofur’s adequate penetration in plasma and subcutaneous tissues following RLP suggests it could be effective in treating distal limb infections, its suboptimal bone penetration calls for further research. This should focus on optimizing drug administration methods or finding alternative treatment options for bone infections. Additionally, disease states may affect the results, and as such, the implications of ceftiofur RLP therapy in such cases also warrant investigation.

Cite This Article

APA
Cox KS, Nelson BB, Wittenburg L, Gold JR. (2016). Plasma, subcutaneous tissue and bone concentrations of ceftiofur sodium after regional limb perfusion in horses. Equine Vet J, 49(3), 341-344. https://doi.org/10.1111/evj.12614

Publication

ISSN: 2042-3306
NlmUniqueID: 0173320
Country: United States
Language: English
Volume: 49
Issue: 3
Pages: 341-344

Researcher Affiliations

Cox, K S
  • Department of Clinical Sciences, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, Colorado, USA.
Nelson, B B
  • Gail Holmes Orthopaedic Research Center, Department of Clinical Sciences, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, Colorado, USA.
Wittenburg, L
  • Flint Animal Cancer Center, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, Colorado, USA.
Gold, J R
  • Department of Clinical Sciences, College of Veterinary Medicine, Washington State University, Pullman, Washington, USA.

MeSH Terms

  • Animals
  • Anti-Bacterial Agents / administration & dosage
  • Anti-Bacterial Agents / blood
  • Anti-Bacterial Agents / metabolism
  • Anti-Bacterial Agents / pharmacokinetics
  • Bone and Bones / chemistry
  • Bone and Bones / metabolism
  • Cephalosporins / administration & dosage
  • Cephalosporins / blood
  • Cephalosporins / metabolism
  • Cephalosporins / pharmacokinetics
  • Female
  • Forelimb
  • Horses / blood
  • Horses / metabolism
  • Male
  • Regional Blood Flow
  • Subcutaneous Tissue / chemistry
  • Subcutaneous Tissue / metabolism
  • Tissue Distribution

Citations

This article has been cited 4 times.
  1. Kuroda T, Minamijima Y, Niwa H, Mita H, Tamura N, Fukuda K, Kuwano A, Sato F. Concentration of cephalothin in body fluids and tissue samples of Thoroughbred horses. J Equine Sci 2022 Sep;33(3):51-54.
    doi: 10.1294/jes.33.51pubmed: 36196140google scholar: lookup
  2. Bonilla AG, Causeret L, Torrent-Crosa A. Pharmacokinetics of ceftiofur in the metacarpophalangeal joint after standing intravenous regional limb perfusion in horses. Can Vet J 2021 Sep;62(9):975-981.
    pubmed: 34475583
  3. Mosichuk AP, Smith JS, Tatarniuk DM, Troy JR, Kreuder AJ. Meropenem Administered via Intravenous Regional Limb Perfusion for Orthopedic Sepsis in Horses: A Clinical Retrospective Study. Front Vet Sci 2021;8:629627.
    doi: 10.3389/fvets.2021.629627pubmed: 33842571google scholar: lookup
  4. Hardefeldt L, Thomas K, Page S, Norris J, Browning G, El Hage C, Stewart A, Gilkerson J, Muscatello G, Verwilghen D, van Galen G, Bauquier J, Cuming R, Reynolds B, Whittaker C, Wilkes E, Clulow J, Burden C, Begg L. Antimicrobial prescribing guidelines for horses in Australia. Aust Vet J 2025 Dec;103(12):781-889.
    doi: 10.1111/avj.70003pubmed: 40903020google scholar: lookup