Moxifloxacin and Ciprofloxacin Protect Human Respiratory Epithelial Cells against Streptococcus pneumoniae, Staphylococcus aureus, Pseudomonas aeruginosa, and Haemophilus influenzae in Vitro

Abstract

The fluoroquinolones moxifloxacin and ciprofloxacin display excellent in vitro activities against many respiratory tract pathogens. Here we show that moxifloxacin and ciprofloxacin accumulate approximately 7- to 10-fold in primary human respiratory epithelial cells, derived from nasal polyps and grown in 3-dimensional vesicles. Furthermore, using these vesicles, we assessed the bactericidal effect of moxifloxacin on Staphylococcus aureus and Streptococcus pneumoniae and that of ciprofloxacin on Pseudomonas aeruginosa and Haemophilus influenzae. Finally, we determined the protective effect of the fluoroquinolones on vesicles infected with these pathogens. All four bacterial strains were highly toxic for vesicles. S. aureus and S. pneumoniae were readily killed by moxifloxacin regardless whether the antibiotics were present intra/extracellularly or only intracellularly in vesicles. Similar results were obtained for the killing of H. influenzae and P. aeruginosa. Exclusively intracellularly located fluoroquinolones rescued 42% to 76% of the cells after bacterial challenge compared to the rescue of 48% to 94% cells when the fluoroquinolones were present intra/ extracellularly. Without addition of fluoroquinolones cell survival in vesicles was 0% to 38%. The results suggest that intracellular accumulation of moxifloxacin and ciprofloxacin is important for the protection of respiratory epithelial cells from the cytotoxic effects of major respiratory tract pathogens.