Inhalation of specific anti-Pseudomonas aeruginosa IgY antibodies transiently decreases P. aeruginosa colonization of the airway in mechanically ventilated piglets

Abstract

Background P. aeruginosa is a pathogen frequently resistant to antibiotics and a common cause of ventilator-associated pneumonia (VAP). Non-antibiotic strategies to prevent or treat VAP are therefore of major interest. Specific polyclonal avian IgY antibodies have previously been shown to be effective against pneumonia caused by P. aeruginosa in rodents and against P. aeruginosa airway colonization in patients. Objectives To study the effect of specific polyclonal anti- P. aeruginosa IgY antibodies ( Pa- IgY) on colonization of the airways in a porcine model. Method The pigs were anesthetized, mechanically ventilated, and subject to invasive hemodynamic monitoring and allocated to either receive 10 9 CFU nebulized P. aeruginosa (control, n = 6) or 10 9 CFU nebulized P. aeruginosa + 200 mg Pa- IgY antibodies (intervention, n = 6). Physiological measurement, blood samples, and tracheal cultures were then secured regularly for 27 h, after which the pigs were sacrificed and lung biopsies were cultured. Results After nebulization, tracheal growth of P. aeruginosa increased in both groups during the experiment, but with lower growth in the Pa- IgY-treated group during the experiment ( p = 0.02). Tracheal growth was 4.6 × 10 3 (9.1 × 10 2 –3.1 × 10 4 ) vs. 4.8 × 10 4 (7.5 × 10 3 –1.4 × 10 5 ) CFU/mL in the intervention group vs. the control group at 1 h and 5.0 × 10 0 (0.0 × 10 0 –3.8 × 10 2 ) vs. 3.3 × 10 4 (8.0 × 10 3 –1.4 × 10 5 ) CFU/mL at 12 h in the same groups. During this time, growth in the intervention vs. control group was one to two orders of ten lower. After 12 h, the treatment effect disappeared and bacterial growth increased in both groups. The intervention group had lower body temperature and cardiac index and higher static compliance compared to the control group. Conclusion In this porcine model, Pa -IgY antibodies lessen bacterial colonization of the airways. Electronic supplementary material The online version of this article (10.1186/s40635-019-0246-1) contains supplementary material, which is available to authorized users.

Bronchially instilled IgY‐antibodies did not decrease pulmonaryp. aeruginosaconcentration in experimental porcine pneumonia

“…After 12 hours a second dose of study drug was given, this was done to compensate for a drop in antibacterial effect after 12 hours seen in our previous study. 12…”

“…11 Also, we have shown that experimental tracheal colonization in pigs is counteracted with nebulized Pa-IgY. 12 We tested the hypothesis that Pa-IgY decreases the concentration of P. aeruginosa in bronchoalveolar lavage (BAL) in experimental porcine pneumonia over 27 hours. We also studied the effect on markers of inflammation, circulatory function, respiration, and kidney function.…”

Bacteriophage Cocktail-Mediated Inhibition of Pseudomonas aeruginosa Biofilm on Endotracheal Tube Surface

“…In addition, P. aeruginosa has shown an enhanced ability to form huge biofilms and to develop antibiotic resistance, which in turn can be considered factors that ensure persistent infection [ 18 , 19 ]. Efforts have been made to reduce complications associated with P. aeruginosa colonization in artificial airways; nonetheless, none of them seem to be largely effective [ 3 , 20 , 21 ].…”

Anti-S1 MERS-COV IgY Specific Antibodies Decreases Lung Inflammation and Viral Antigen Positive Cells in the Human Transgenic Mouse Model

“…In 2008, the European Medicines Agency granted an orphan drug designation to IgY antibodies for the treatment of P. aeruginosa infections associated with cystic fibrosis [ 43 ]. A recent study demonstrated that IgY antibodies transiently decreased P. aeruginosa colonization of the airway in mechanically ventilated piglets [ 44 ]. Moreover, specific IgY antibodies could protect mice against pneumonia caused by Acinetobacter baumannii [ 43 ].…”