Azithromycin is effective against intracellular infections of Francisella philomiragia, F. novicida, and F. LVS
ABSTRACT Francisella tularensis is a gram-negative coccobacillus that causes zoonotic diseases in rodents and hares. Humans infected with F. tularensis develop tularemia disease resulting in flu-like symptoms and enlarged lymph nodes. Macrolides, such as azithromycin, are common antibiotics given for respiratory illnesses. These antibiotics concentrate in macrophages, and may be useful for the treatment of tularemia. Azithromycin was added in vitro for F. philomiragia, F. novicida, and F. LVS to show antibiotic susceptibility at low concentrations for F. philomiragia and F. novicida (<0.5 µg/ml Az) and at high concentrations for F. LVS (<20.0 µg/ml Az). J774a.1 mouse macrophage and A549 human epithelial cells were infected with F. philomiragia, F. novicida, and F. LVS and treated with different azithromycin concentrations. Azithromycin was found to be effective against the F. novicida, F. philomiragia, and F. LVS intracellular infections at 5.0 µg/ml azithromycin in J774a.1 and at 25.0 µg/ml azithromycin in A549 cells. An HPLC approach will be used to determine the azithromycin intracellular concentration for J774a.1 after 24 hour treatment of 5.0 µg/ml azithromycin dose administered and for A549 cells after 24 hour treatment of 25.0 µg/ml dose. We have demonstrated that azithromycin is effective in treating F. philomiragia and F. novicida infection of eukaryotic cells and F. LVS at higher concentrations. These studies may give motivation to develop a newer generation of azithromycin which retains its intramacrophage concentration and perhaps has higher effectiveness against Francisella . |
