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Safety and efficacy of a bacteriophage cocktail in an in vivo model of sinusitis

Fonga SA, Drillinga AJ, Ooia ML et al. Safety and efficacy of a bacteriophage cocktail in an in vivo model of Pseudomonas aeruginosa sinusitis // Translational Research, Available online 19 December 2018 https://doi.org/10.1016/j.trsl.2018.12.002

 

The aims of this study were to assess the safety and efficacy of a Pseudomonas aeruginosa  (PA) phage cocktail (CT-PA) in a sheep model of rhinosinusitis. The sheep rhinosinusitis model was adapted to simulate PA infection in sheep frontal sinuses. To assess efficacy, after a 7-day biofilm formation period, sheep received twice-daily frontal trephine flushes of CT-PA or saline for 1 week. Biofilm quantitation on frontal sinus mucosa was performed using LIVE/DEAD BacLight staining.

To assess safety, sheep received twice-daily frontal trephine flushes of CT-PA or vehicle control for 3 weeks. Blood and fecal samples were collected throughout treatment. Histopathology of frontal sinus, lung, heart, liver, spleen, and kidney tissue was performed. Sinus cilia were visualized using scanning electron microscopy (SEM). The Efficacy arm showed a statistically significant reduction in biofilm biomass with all concentrations of CT-PA tested (P < 0.05). Phage presence in sinuses was maintained for at least 16 hours after the final flush.

All Safety arm sheep completed 3 weeks of treatment. Phage was detected consistently in feces and sporadically in blood and organ samples. Histology and SEM of tissues revealed no treatment-related damage. In conclusion, CT-PA was able to decrease sinus PA biofilm at concentrations of 108–1010 PFU/mL. No safety concerns were noted.