Disposition of oral telithromycin in foals and in vitro activity of the drug against macrolide-susceptible and macrolide-resistant Rhodococcus equi isolates.
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).
Javsicas
L H
LH
Department of Large Animal Medicine, College of Veterinary Medicine, University of Georgia, Athens, GA 30602, USA.
Giguère
S
S
Womble
Ariel Y
AY
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*
D000900:Anti-Bacterial Agents; D048628:Ketolides; D018942:Macrolides; D004917:Erythromycin; D017963:Azithromycin; D017291:Clarithromycin; C106791:telithromycin