Azithromycin potentiates avian IgY effect against Pseudomonas aeruginosa in a murine pulmonary infection model
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Azithromycin potentiates avian IgY effect against Pseudomonas aeruginosa in a murine pulmonary infection model. / Thomsen, Kim; Christophersen, Lars; Lerche, Christian Johann; Holmgaard, Dennis Back; Calum, Henrik; Høiby, Niels; Moser, Claus.
In: International Journal of Antimicrobial Agents, Vol. 57, No. 1, 106213, 2021.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Azithromycin potentiates avian IgY effect against Pseudomonas aeruginosa in a murine pulmonary infection model
AU - Thomsen, Kim
AU - Christophersen, Lars
AU - Lerche, Christian Johann
AU - Holmgaard, Dennis Back
AU - Calum, Henrik
AU - Høiby, Niels
AU - Moser, Claus
PY - 2021
Y1 - 2021
N2 - 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 owing 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. Evaluation of phagocytic cell capacity was performed using in vitro exposure of azithromycin pre-treated human polymorphonuclear neutrophils 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. Combined azithromycin treatment and IgY opsonisation significantly increased bacterial killing compared with the two single-treated groups and controls. In vivo, 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 1 beta (IL-1β) paralleled this effect. Combination of azithromycin and anti-Pseudomonas IgY potentiated the killing and pulmonary elimination of P. aeruginosa in vitro and in vivo. The augmented effect of combinatory treatment with azithromycin and IgY constitutes a potential clinical application for improving anti-Pseudomonas strategies.
AB - 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 owing 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. Evaluation of phagocytic cell capacity was performed using in vitro exposure of azithromycin pre-treated human polymorphonuclear neutrophils 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. Combined azithromycin treatment and IgY opsonisation significantly increased bacterial killing compared with the two single-treated groups and controls. In vivo, 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 1 beta (IL-1β) paralleled this effect. Combination of azithromycin and anti-Pseudomonas IgY potentiated the killing and pulmonary elimination of P. aeruginosa in vitro and in vivo. The augmented effect of combinatory treatment with azithromycin and IgY constitutes a potential clinical application for improving anti-Pseudomonas strategies.
KW - Avian IgY
KW - Azithromycin
KW - Cystic fibrosis
KW - In vivo
KW - Pseudomonas aeruginosa
U2 - 10.1016/j.ijantimicag.2020.106213
DO - 10.1016/j.ijantimicag.2020.106213
M3 - Journal article
C2 - 33256950
AN - SCOPUS:85096881613
VL - 57
JO - International Journal of Antimicrobial Agents
JF - International Journal of Antimicrobial Agents
SN - 0924-8579
IS - 1
M1 - 106213
ER -
ID: 252681267