Azithromycin potentiates avian IgY effect against Pseudomonas aeruginosa in a murine pulmonary infection model

Abstract Introduction Cystic fibrosis (CF) patients are at risk of acquiring chronic Pseudomonas aeruginosa lung infections. The biofilm mode of growth of P. aeruginosa induces tolerance to antibiotics and the host response; accordingly, treatment failure occurs. Supplemental azithromycin has proven beneficial in CF due to potential immunomodulatory mechanisms. Clinical studies have demonstrated a reduction in exacerbations in CF patients by Avian IgY anti-pseudomonas immunotherapy. We hypothesise that azithromycin pre-treatment could potentiate the observed anti-pseudomonas effect of IgY opsonisation in vivo. Materials and methods Evaluation of phagocytic cell capacity was performed using in vitro exposure of azithromycin pre-treated human polymorphonuclear neutrophils (PMNs) to IgY opsonised P. aeruginosa PAO3. A murine lung infection model using nasal planktonic P. aeruginosa inoculation and successive evaluation 24 h post-infection was used to determine lung bacteriology and subsequent pulmonary inflammation. Results Combined azithromycin treatment and IgY opsonisation significantly increased bacterial killing as compared to the two single-treated groups and controls. In vivo, a significantly increased bacterial pulmonary elimination was revealed by combining azithromycin and IgY. A reduction in the inflammatory markers mobiliser granulocyte colony-stimulating factor (G-CSF), macrophage inflammatory protein-2 (MIP-2) and interleukin (IL)-1b paralleled this effect. Conclusion Combination of azithromycin and anti-pseudomonas IgY potentiated the killing and pulmonary elimination of P. aeruginosa in vitro as well as in vivo. The augmented effect of combinatory treatment with azithromycin and IgY constitute a potential clinical application for improving anti-pseudomonas strategies.