Intracellular Concentrations of Fosfomycin in Alveolar Macrophages from Weaning Piglets

摘要

At weaning, piglets are more susceptible to infectious diseases, being respiratory syndromes one of the most frequent conditions. Fosfomycin is indicated for the treatment of a variety of porcine bacterial pathogens, with MIC90 ranging between 0.25-0.50 μg mL?1. Fosfomycin exhibits a time-dependent killing. Thus, killing of bacteria occurs when its concentrations remain constantly above the MIC. Fosfomycin concentrations in respiratory cells and epithelial lining fluid of pigs have already been studied. Although, fosfomycin showed clinical efficacy in the treatment of pulmonary diseases, concentrations in alveolar macrophages (biophase for facultative and obligate intracellular microorganisms) have not been established in any species. The present study determined the intracellular concentrations of disodium fosfomycin in alveolar macrophages after a single IM dose of 15 mg kg?1 in the gluteal muscle. Concentrations ranged from 0.14-1.52 μg mL?1, being lower than those found in epithelial lining fluid (49.03%) and respiratory cells (54.48%). The Cmax was 1.52 μg mL?1 and Tmax was 4 h. Concentrations exceeded the MIC90 for most pathogens of importance in pig production for up to six hours (T>MIC = 6 h). Therefore, fosfomycin may be useful in the treatment of lung infections caused by facultative intracellular microorganisms.