title: Efficacy of trimethoprim-sulfadoxine against Escherichia coli in a tissue cage model in calves.
abstract: Tissue cages implanted subcutaneously in calves were infected with Escherichia coli. Twenty-four hours later, the calves were treated either with single doses of 2.5 + 12.5 or 5 + 25 mg/kg trimethoprim (TMP) + sulfadoxine (SDX) or with five doses of 7.5 + 37.5 mg/kg TMP + SDX at 12-h intervals. In addition, one cage in each of three calves in the highest dose group was infected 3 h after initiation of treatment. Untreated calves were kept as controls. Concentrations of TMP and SDX in plasma and tissue cage fluid (TCF) and counts of viable bacteria in TCF were determined. In the highest dose group, concentrations of TMP in TCF remained above the minimum inhibitory concentration of the test strain for 94-101 h and peak to minimum inhibitory concentration (MIC) ratio was close to 10. In spite of this, an effect of treatment was noted only in cages infected after initiation of treatment. In vitro studies and analysis of thymidine content in serum and TCF from calves suggest that levels of thymidine in TCF are high enough to antagonize the antibacterial effect of TMP. The results indicate that soft tissue infections in secluded infection sites of calves are refractory to treatment with TMP + SDX.
authors.affiliation: Department of Antibiotics, National Veterinary Institute (SVA), SE-751 89 Uppsala, Sweden. christiana.greko@sva.se
authors.forename: C
authors.initials: C
authors.lastname: Greko
authors.forename: B
authors.initials: B
authors.lastname: Bengtsson
authors.forename: A
authors.initials: A
authors.lastname: Franklin
authors.forename: S-O
authors.initials: SO
authors.lastname: Jacobsson
authors.forename: B
authors.initials: B
authors.lastname: Wiese
authors.forename: J
authors.initials: J
authors.lastname: Luthman
mesh_terms: D000818:Animals; D019540:Area Under Curve; D002417:Cattle; D002851:Chromatography, High Pressure Liquid; D004338:Drug Combinations; D004927:Escherichia coli Infections / Q000188:drug therapy*; D006207:Half-Life; D008657:Metabolic Clearance Rate; D008826:Microbial Sensitivity Tests; D013413:Sulfadoxine / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use*; D013936:Thymidine / Q000097:blood; D014295:Trimethoprim / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use*
chemical_list: D004338:Drug Combinations; C000301:trimethoprim, sulfadoxine drug combination; D013413:Sulfadoxine; D014295:Trimethoprim; D013936:Thymidine