In vitro penetration of Fosfomycin in respiratory cells

Abstract

Infectious diseases of the respiratory system are important in intensive swine production. Fosfomycin is a widely used antibiotic for the treatment of swine lung infections. The aim of this research was to study the penetration of fosfomycin in an in vitro model of respiratory cells (HEp-2 cells). Cell cultures were subjected to four treatments: a) negative control; b) disodium fosfomycin (280µg/mL); c) disodium fosfomycin (130µg/mL) and d) calcium fosfomycin (130µg/mL). Intracellular concentrations of fosfomycin were analysed by high-performance liquid chromatography tandem mass spectrometry (HPLC MS/MS). Concentrations in HEp-2 cells incubated with 280µg/mL of disodium fosfomycin ranged from 0.74 to 2.79µg/mL (Tmax: 12 hours). When incubated with the same formulation of fosfomycin at a concentration of 130µg/mL, intracellular concentrations ranged between 0.31 and 1.60µg/mL (Tmax: 12 hours). Calcium fosfomycin reached intracellular concentrations that varied between 0.46 and 1.11µg/mL (Tmax: 8 hours). Fosfomycin concentrations exceeded the MIC90 for the most important pathogens in swine respiratory infections (Streptococcus spp.; 0.25µg/mL). Therefore, it is apparent that fosfomycin is an alternative for the treatment of intracellular respiratory infections in pigs.