Serum and synovial fluid steady-state concentrations of trimethoprim and sulfadiazine in horses with experimentally induced infectious arthritis.
Abstract: The tarsocrural joints of 11 horses were inoculated with 1.2 to 2.16 x 10(6) viable Staphylococcus aureus organisms susceptible to a trimethoprim-sulfadiazine (TMP-SDZ) combination with minimal inhibitory concentration (MIC) of 0.25 micrograms of TMP/ml and 4.75 micrograms of SDZ/ml. Antimicrobial treatment consisted of oral administration of a TMP-SDZ combination--30 mg/kg of body weight given once daily (group-1 horses) or 60 mg/kg given as 30 mg/kg every 12 hours (group-2 horses). Paired serum and synovial fluid samples were obtained before intra-articular inoculation with the S aureus, after inoculation with S aureus but before antimicrobial treatment, and after inoculation at various hourly intervals after oral administration of the TMP-SDZ combination. The TMP-SDZ combination was administered daily in the 2 dosages for 21 days. Samples were collected after day 3 of repetitive drug administration so that drug steady-state concentration would have been achieved. Serum and synovial fluid samples were analyzed for TMP and SDZ concentrations. Administration of the TMP-SDZ combination at a dosage of 30 mg/kg once daily was not effective in maintaining TMP or SDZ concentrations above the MIC of TMP-SDZ for the S aureus (0.25 and 4.75 micrograms/ml for TMP and SDZ, respectively) in the infected synovial fluid or in maintaining adequate TMP concentration in the serum. The alternative use of the TMP-SDZ combination at a dosage of 60 mg/kg given as 30 mg/kg every 12 hours was effective in maintaining serum and synovial fluid concentrations of TMP and SDZ that were greater than the MIC for the infective organism.(ABSTRACT TRUNCATED AT 250 WORDS)
Publication Date: 1988-10-01 PubMed ID: 3189982
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- Journal Article
- Research Support
- U.S. Gov't
- Non-P.H.S.
Summary
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The research article investigates the effect of various dosages of the combined drugs trimethoprim and sulfadiazine on horses with experiments-induced infectious arthritis. It concludes that a higher twice-daily dosage of the medicine was effective in maintaining therapeutic chemical concentrations in the blood and fluid of the infected joint.
Research Context
- The research seeks to evaluate the efficacy of the antibiotics trimethoprim (TMP) and sulfadiazine (SDZ) in treating infectious arthritis in horses.
- The study focuses particularly on the concentrations of TMP and SDZ in the blood (serum) and joint fluid (synovial fluid) of horses inflicted with arthritis.
Methodology
- The tarsocrural joints (a joint in the hock of the horse) of eleven horses were infected with Staphylococcus aureus bacteria, which were proven susceptible to the TMP-SDZ combination with a certain minimum inhibitory concentration (MIC).
- The MIC, the lowest concentration of the drug that prevents bacterial growth, was determined to be 0.25 micrograms/ml of TMP and 4.75 micrograms/ml of SDZ.
- The researchers administrated the TMP-SDZ combination orally in two different dosages: 30 mg/kg body weight once daily, and 60 mg/kg divided into two doses of 30 mg/kg every 12 hours.
- Samples of blood and joint fluid were taken before infection, after infection but before the treatment, and at different times after the treatment has begun.
- The samples were taken three days after continuous drug administration, at which point a steady-state concentration of the drugs in the body would have been reached.
Results and Conclusion
- The lower dosage of the TMP-SDZ combination (30 mg/kg once daily) was concluded to be ineffective as it failed to maintain TMP or SDZ concentrations above the MIC in the infected joint fluid or the blood serum.
- The higher dosage (60 mg/kg given as two doses of 30 mg/kg) proved effective in maintaining drug concentrations in the serum and joint fluid above the MIC for the infective bacteria.
- The study concludes that the higher dosage, administered twice a day, could be the more effective regimen to sustain therapeutic drug concentrations in both serum and synovial fluid for horses suffering from bacterial arthritis.
Cite This Article
APA
Bertone AL, Jones RL, McIlwraith CW.
(1988).
Serum and synovial fluid steady-state concentrations of trimethoprim and sulfadiazine in horses with experimentally induced infectious arthritis.
Am J Vet Res, 49(10), 1681-1687.
Publication
Researcher Affiliations
- Department of Clinical Sciences, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins 80523.
MeSH Terms
- Administration, Oral
- Animals
- Anti-Bacterial Agents / administration & dosage
- Anti-Bacterial Agents / blood
- Anti-Bacterial Agents / pharmacokinetics
- Arthritis, Infectious / drug therapy
- Arthritis, Infectious / metabolism
- Arthritis, Infectious / veterinary
- Disease Models, Animal
- Drug Combinations / administration & dosage
- Drug Combinations / blood
- Drug Combinations / pharmacokinetics
- Horse Diseases / drug therapy
- Horse Diseases / metabolism
- Horses
- Staphylococcal Infections / drug therapy
- Staphylococcal Infections / metabolism
- Staphylococcal Infections / veterinary
- Staphylococcus aureus
- Sulfadiazine / administration & dosage
- Sulfadiazine / blood
- Sulfadiazine / pharmacokinetics
- Synovial Fluid / metabolism
- Trimethoprim / administration & dosage
- Trimethoprim / blood
- Trimethoprim / pharmacokinetics
Citations
This article has been cited 1 times.- Gustafsson K, Tatz AJ, Dahan R, Abu Ahmad W, Britzi M, Sutton GA, Kelmer G. Synovial Concentration of Trimethoprim-Sulphadiazine Following Regional Limb Perfusion in Standing Horses. Animals (Basel) 2021 Jul 13;11(7).
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