Serum and synovial fluid steady-state concentrations of trimethoprim and sulfadiazine in horses with experimentally induced infectious arthritis.
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)
Bertone
A L
AL
Department of Clinical Sciences, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins 80523.
Jones
R L
RL
McIlwraith
C W
CW
D000284:Administration, Oral; D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D001170:Arthritis, Infectious / Q000188:drug therapy / Q000378:metabolism / Q000662:veterinary*; D004195:Disease Models, Animal; D004338:Drug Combinations / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics; D006734:Horse Diseases / Q000188:drug therapy / Q000378:metabolism*; D006736:Horses; D013203:Staphylococcal Infections / Q000188:drug therapy / Q000378:metabolism / Q000662:veterinary*; D013211:Staphylococcus aureus; D013411:Sulfadiazine / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D013582:Synovial Fluid / Q000378:metabolism; D014295:Trimethoprim / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D000096926:Benzenesulfonamides
D000900:Anti-Bacterial Agents; D004338:Drug Combinations; D013411:Sulfadiazine; D014295:Trimethoprim; C024873:sulfadiazine, trimethoprim drug combination; D000096926:Benzenesulfonamides