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).
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