Meropenem synovial fluid concentrations after intravenous regional limb perfusion in standing horses.
Abstract: To determine meropenem concentrations in radiocarpal (RC) joint fluid and plasma after intravenous regional limb perfusion (IVRLP). Methods: In vivo experimental study. Methods: Nine healthy adult mares. Methods: Meropenem (500 mg) was injected in the forelimb of standing sedated horses via IVRLP with a pneumatic tourniquet inflated to 400 mmHg. Synovial fluid was collected from RC joints at 0, 0.5, 1, 2, 4, 6, 8, 12, and 18 hours after meropenem injection. Blood samples were collected from the jugular vein at the same time points and at 5 and 15 minutes following injection. Meropenem concentrations were determined by using a microbiological bioassay. Results: Median synovial fluid concentrations reached a time of maximum synovial fluid concentration 0.5 hours after IVRLP. Synovial fluid concentrations varied greatly, with a mean maximum synovial fluid concentration of 25.6 µg/mL (range, below limit of quantitation to 75.5). Concentrations remained above the breakpoint for susceptibility (1 µg/mL) for 3 hours (last nonzero concentration measured, median) and 4.1 hours (predicted, mean). Concentrations >6 µg/mL were measured for 2 hours (observed, median) and 1.7 hours (predicted, mean). Six horses had mild swelling at the injection site. Conclusions: Administration of 500 mg meropenem resulted in highly variable concentrations between horses and achieved levels above clinically relevant minimum inhibitory concentration for a minor portion of a once-daily dosing interval. Conclusions: If time-dependent pharmacodynamics apply, IVRLP with 500 mg of meropenem may be ineffective and would likely promote resistance.
© 2018 The American College of Veterinary Surgeons.
Publication Date: 2018-07-31 PubMed ID: 30066453DOI: 10.1111/vsu.12940Google Scholar: Lookup
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- Journal Article
Summary
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The research article investigates the concentrations of the antibiotic meropenem in joint fluid and blood plasma of horses after administering through intravenous regional limb perfusion (IVRLP). The research found notable variation in meropenem concentrations among horses and concluded that the method used might not be effective and could potentially contribute to drug resistance.
Methods
- The study involved an in vivo experiment performed on nine healthy adult mares.
- Meropenem (500 mg) was administered into the forelimb of sedated horses through intravenous regional limb perfusion (IVRLP), under an inflated pneumatic tourniquet set at 400 mmHg.
- Synovial fluid samples were taken from the radiocarpal (RC) joints at different time intervals after meropenem administration – 0, 0.5, 1, 2, 4, 6, 8, 12, and 18 hours.
- Concurrently, blood samples were taken from the jugular vein also at specific time points, additionally including 5 and 15 minutes after injection.
- A microbiological bioassay was used to determine the meropenem concentrations in the samples.
Results
- Median synovial fluid concentrations reached their peak 0.5 hours after IVRLP.
- The concentrations of meropenem in synovial fluid varied greatly, with an average peak concentration at 25.6 µg/mL. The range stretched from below the limit of quantitation to 75.5 µg/mL.
- The concentration remained above the breakpoint for susceptibility (1 µg/mL) for about 3 to 4 hours.
- Concentrations above 6 µg/mL were observed for approximately 1.7 to 2 hours.
- Swelling at the injection site was observed in six out of the nine horses.
Conclusions
- The administration of 500 mg of meropenem resulted in highly variable concentrations between horses, and only achieved levels surpassing the clinically relevant minimum inhibitory concentration for a partial interval of once-daily dosing.
- If time-dependent pharmacodynamics is considered, IVRLP with 500 mg dose of meropenem may possibly be ineffective and could contribute to the development of drug resistance.
Cite This Article
APA
Fontenot RL, Langston VC, Zimmerman JA, Wills RW, Sloan PB, Mochal-King CA.
(2018).
Meropenem synovial fluid concentrations after intravenous regional limb perfusion in standing horses.
Vet Surg, 47(6), 852-860.
https://doi.org/10.1111/vsu.12940 Publication
Researcher Affiliations
- Department of Clinical Sciences, College of Veterinary Medicine, Mississippi State University, Mississippi State, Mississippi.
- Department of Clinical Sciences, College of Veterinary Medicine, Mississippi State University, Mississippi State, Mississippi.
- Department of Clinical Sciences, College of Veterinary Medicine, Mississippi State University, Mississippi State, Mississippi.
- Department of Pathobiology and Population Medicine, College of Veterinary Medicine, Mississippi State University, Mississippi State, Mississippi.
- Department of Clinical Sciences, College of Veterinary Medicine, Mississippi State University, Mississippi State, Mississippi.
- Department of Clinical Sciences, College of Veterinary Medicine, Mississippi State University, Mississippi State, Mississippi.
MeSH Terms
- Administration, Intravenous / veterinary
- Animals
- Anti-Bacterial Agents / administration & dosage
- Anti-Bacterial Agents / metabolism
- Female
- Forelimb / blood supply
- Horses / metabolism
- Meropenem / administration & dosage
- Meropenem / metabolism
- Perfusion / veterinary
- Synovial Fluid / chemistry
Grant Funding
- Mississippi State University College of Veterinary Medicine Office of Research and Graduate Studies
Citations
This article has been cited 2 times.- Redding LE, Elzer EJ, Ortved KF. Effects of regional limb perfusion technique on concentrations of antibiotic achieved at the target site: A meta-analysis. PLoS One 2022;17(4):e0265971.
- 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.
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