Plasma pharmacokinetics, pulmonary distribution, andin vitroactivity of gamithromycin in foals

Abstract

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.

Efficacy of Gamithromycin for the Treatment of Foals with Mild to Moderate Bronchopneumonia

“…In a previous study, administration of a single dose of GAM by the same route to 6 foals did not result in adverse reactions 10. The transient hind limb lamenesses observed in many foals the present study are likely the result of the irritating nature of the drug.…”

“…Although the etiology of the pulmonary lesions could not be determined, the presents study is an accurate reflection of what is occurring in clinical practice because tracheobronchial aspirates are not typically performed as part of ultrasonographic screening programs 52, 3 and these microorganisms are typically susceptible to macrolides, azalides, and rifampin 10, 20…”

Prevention and treatment of Rhodococcus equi infection in foals: an update

“…Gamithromycin (6 mg/kg administered intramuscularly every seven days) has shown in vitro efficacy and anecdotally has been effective in the treatment of foals with presumed R equi pneumonia (Berghaus and others 2012). Neither tulathromycin nor tilmicosin can be recommended due to reported poor in vitro efficacy, equivocal in vivo efficacy and/or injection site reactions (Giguère and others 2011).…”

Basics of antimicrobial therapy for the horse

“…zooepidemicus and R. equi, respectively, for 7 days [43]. Tilmicosin should not be used in horses because of poor bioavailability when administered orally and safety concerns following parenteral administration.…”