title: Disposition of oral telithromycin in foals and in vitro activity of the drug against macrolide-susceptible and macrolide-resistant Rhodococcus equi isolates.
abstract: The objectives of this study were to determine the serum and pulmonary disposition of telithromycin in foals and to determine the minimum inhibitory concentration (MIC) of telithromycin against macrolide-susceptible and macrolide-resistant Rhodococcus equi isolates. A single dose of telithromycin (15 mg/kg of body weight) was administered to six healthy 6-10-week-old foals by the intragastric route. Activity of telithromycin was measured in serum, pulmonary epithelial lining fluid (PELF), and bronchoalveolar lavage (BAL) cells using a microbiological assay. The broth macrodilution method was used to determine the MIC of telithromycin, azithromycin, clarithromycin and erythromycin against R. equi. Following intragastric administration, mean +/- SD time to peak serum telithromycin activity (T(max)) was 1.75 +/- 0.76 h, maximum serum activity (C(max)) was 1.43 +/- 0.37 microg/mL, and terminal half-life (t(1/2)) was 3.81 +/- 0.40 h. Telithromycin activity, 4 h postadministration was significantly higher in BAL cells (50.9 +/- 14.5 microg/mL) than in PELF (5.07 +/- 2.64 microg/mL), and plasma (0.84 +/- 0.25 microg/mL). The MIC(90) of telithromycin for macrolide-resistant R. equi isolates (8 microg/mL) was significantly higher than that of macrolide-susceptible isolates (0.25 microg/mL). The MIC of telithromycin for macrolide-resistant isolates (MIC(50)=4.0 microg/mL) was significantly lower than that of clarithromycin (MIC(50)=24.0 microg/mL), azithromycin (MIC(50)=256 microg/mL) and erythromycin (MIC(50)=24 microg/mL).
authors.affiliation: Department of Large Animal Medicine, College of Veterinary Medicine, University of Georgia, Athens, GA 30602, USA.
authors.forename: L H
authors.initials: LH
authors.lastname: Javsicas
authors.forename: S
authors.initials: S
authors.lastname: Giguère
authors.forename: Ariel Y
authors.initials: AY
authors.lastname: Womble
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000900:Anti-Bacterial Agents / Q000097:blood / Q000493:pharmacokinetics* / Q000494:pharmacology; D017963:Azithromycin / Q000493:pharmacokinetics; D018893:Bronchoalveolar Lavage / Q000662:veterinary; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D017291:Clarithromycin / Q000493:pharmacokinetics; D024881:Drug Resistance, Bacterial; D004848:Epithelium / Q000378:metabolism; D004917:Erythromycin / Q000493:pharmacokinetics; D005260:Female; D006736:Horses; D048628:Ketolides / Q000097:blood / Q000493:pharmacokinetics* / Q000494:pharmacology; D016014:Linear Models; D008168:Lung / Q000378:metabolism*; D018942:Macrolides / Q000494:pharmacology*; D008297:Male; D008826:Microbial Sensitivity Tests / Q000662:veterinary; D016929:Rhodococcus equi / Q000187:drug effects*
chemical_list: D000900:Anti-Bacterial Agents; D048628:Ketolides; D018942:Macrolides; D004917:Erythromycin; D017963:Azithromycin; D017291:Clarithromycin; C106791:telithromycin