Alexander Otterbeck: Treatment of Pseudomonas aeruginosa using immunoglobulin Y: A porcine experimental model of ventilator-associated pneumonia and septic shock caused by P. aeruginosa

Abstract

Background: Ventilator associated pneumonia (VAP) caused by Pseudomonas aeruginosa is a common cause of morbidity and mortality in patients treated in the intensive care unit. The spread of pathogens with anti-microbial resistance mandates the investigation of novel therapeutic strategies. We hypothesized that specific polyclonal anti-P. aeruginosa IgY-antibodies (Pa-IgY) can be used as a treatment for tracheal colonization, VAP and septic shock caused by P. aeruginosa.

Objectives: The objective of this project was to investigate if treatment with Pa-IgY decreases the bacterial concentration of P. aeruginosa in a model of tracheal colonization, in experimental VAP and in experimental septic shock with bacteremia.

Method: We have performed four experiments. The experiments are porcine models with anesthetized and mechanically ventilated pigs.

In the first experiment a model of tracheal colonization was achieved by nebulizing P. aeruginosa. Treatment with Pa-IgY was then also administered as a nebulization.

In the second experiment a pulmonary instillation of P. aeruginosa was used to simulate VAP. Treatment with Pa-IgY was then administered with the same method of instillation.

In the third experiment the same model was used as in experiment number two. Pa-IgY was then administered as an intravenous bolus dose.

In the fourth experiment, P. aeruginosa bacteremia and septic shock was treated with an intravenous bolus of Pa-IgY.

Results: In experiment number one, treatment with Pa-IgY decreased the concentration of P. aeruginosa in lower airway-cultures. In the second and third experiment we saw no effect on airway concentration of P. aeruginosa. In experiment number four the blood concentration of P. aeruginosa increased when using Pa-IgY.

Conclusion: We conclude that there is evidence that Pa-IgY can be used to decrease airway colonization by P. aeruginosa. In our experimental model of VAP, Pa-IgY has no effect on airway concentration of P. aeruginosa. When used to treat bacteremia Pa-IgY may increase blood bacterial concentration.