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  • Author or Editor: Elise Lee x
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Abstract

Objective—To determine pharmacokinetics of clarithromycin and concentrations in body fluids and bronchoalveolar (BAL) cells of foals.

Animals—6 healthy 2-to 3-week-old foals.

Procedures—In a crossover design, clarithromycin (7.5 mg/kg) was administered to each foal via IV and intragastric (IG) routes. After the initial IG administration, 5 additional doses were administered IG at 12-hour intervals. Concentrations of clarithromycin and its 14-hydroxy metabolite were measured in serum by use of high-performance liquid chromatography. A microbiologic assay was used to measure clarithromycin activity in serum, urine, peritoneal fluid, synovial fluid, CSF, pulmonary epithelial lining fluid (PELF), and BAL cells.

Results—After IV administration, elimination half-life (5.4 hours) and mean ± SD body clearance (1.27 ± 0.25 L/h/kg) and apparent volume of distribution at steady state (10.4 ± 2.1 L/kg) were determined for clarithromycin. The metabolite was detected in all 6 foals by 1 hour after clarithromycin administration. Oral bioavailability of clarithromycin was 57.3 ± 12.0%. Maximum serum concentration of clarithromycin after multiple IG administrations was 0.88 ± 0.19 μg/mL. After IG administration of multiple doses, clarithromycin concentrations in peritoneal fluid, CSF, and synovial fluid were similar to or lower than concentrations in serum, whereas concentrations in urine, PELF, and BAL cells were significantly higher than concentrations in serum.

Conclusions and Clinical Relevance—Oral administration of clarithromycin at 7.5 mg/kg every 12 hours maintains concentrations in serum, PELF, and BAL cells that are higher than the minimum inhibitory concentration (0.12 μg/mL) for Rhodococcus equiisolates for the entire 12-hour dosing interval.

Full access
in American Journal of Veterinary Research

Abstract

Objective—To determine the prevalence of antimicrobial resistance to macrolide antimicrobials or rifampin in Rhodococcus equi isolates and to describe treatment outcome in foals infected with antimicrobial-resistant isolates of R equi.

Design—Cross-sectional study.

Sample Population—38 isolates classified as resistant to macrolide antimicrobials or rifampin received from 9 veterinary diagnostic laboratories between January 1997 and December 2008.

Procedures—For each isolate, the minimum inhibitory concentration of macrolide antimicrobials (ie, azithromycin, erythromycin, and clarithromycin) and rifampin was determined by use of a concentration-gradient test. Prevalence of R equi isolates from Florida and Texas resistant to macrolide antimicrobials or rifampin was determined. Outcome of antimicrobial treatment in foals infected with antimicrobial-resistant isolates of R equi was determined.

Results—Only 24 of 38 (63.2%) isolates were resistant to > 1 antimicrobial. Two isolates were resistant only to rifampin, whereas 22 isolates were resistant to azithromycin, erythromycin, clarithromycin, and rifampin. The overall prevalence of antimicrobial-resistant isolates in submissions received from Florida and Texas was 3.7% (12/328). The survival proportion of foals infected with resistant R equi isolates (2/8 [25.0%]) was significantly less, compared with the survival proportion in foals that received the same antimicrobial treatment from which antimicrobial-susceptible isolates were cultured (55/79 [69.6%]). Odds of nonsurvival for foals infected with resistant R equi isolates were 6.9 (95% confidence interval, 1.3 to 37) times the odds for foals infected with susceptible isolates.

Conclusions and Clinical Relevance—Interpretation of the results emphasized the importance of microbiological culture and antimicrobial susceptibility testing in foals with pneumonia caused by R equi.

Full access
in Journal of the American Veterinary Medical Association