The objectives of this study were to determine the plasma and pulmonary disposition of
gamithromycin in foals and to investigate the in vitro activity of the
drug against Streptococcus equi subsp. zooepidemicus (S. zooepidemicus) and Rhodococcus equi. A single dose of
gamithromycin (6 mg/kg of
body weight) was administered intramuscularly. Concentrations of
gamithromycin in plasma, pulmonary epithelial lining fluid (PELF), bronchoalveolar lavage (BAL) cells, and blood neutrophils were determined using HPLC with tandem mass spectrometry detection. The minimum inhibitory concentration of
gamithromycin required for growth inhibition of 90% of R. equi and S. zooepidemicus isolates (MIC(90)) was determined. Additionally, the activity of
gamithromycin against intracellular R. equi was measured. Mean peak
gamithromycin concentrations were significantly higher in blood neutrophils (8.35±1.77 μg/mL) and BAL cells (8.91±1.65 μg/mL) compared with PELF (2.15±2.78 μg/mL) and plasma (0.33±0.12 μg/mL). Mean terminal half-lives in neutrophils (78.6 h), BAL cells (70.3 h), and PELF (63.6 h) were significantly longer than those in plasma (39.1 h). The MIC(90) for S. zooepidemicus isolates was 0.125 μg/mL. The MIC of
gamithromycin for
macrolide-resistant R. equi isolates (MIC(90)=128 μg/mL) was significantly higher than that for
macrolide-susceptible isolates (1.0 μg/mL). The activity of
gamithromycin against intracellular R. equi was similar to that of
azithromycin and
erythromycin. Intramuscular administration of
gamithromycin at a dosage of 6 mg/kg would maintain PELF concentrations above the MIC(90) for S. zooepidemicus and phagocytic cell concentrations above the MIC(90) for R. equi for approximately 7 days.