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Transl Res. 2019 Apr;206:41-56. doi: 10.1016/j.trsl.2018.12.002. Epub 2018 Dec 19.

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

Author information

1
Department of Surgery - Otolaryngology Head and Neck Surgery, The Queen Elizabeth Hospital, University of Adelaide, Woodville South, South Australia, Australia.
2
Adelaide Medical School, University of Adelaide, Adelaide, South Australia, Australia.
3
AmpliPhi Australia, Sydney, New South Wales, Australia.
4
Department of Surgery - Otolaryngology Head and Neck Surgery, The Queen Elizabeth Hospital, University of Adelaide, Woodville South, South Australia, Australia. Electronic address: peterj.wormald@adelaide.edu.au.

Abstract

Pseudomonas aeruginosa (PA) is a bacterial pathogen that frequently displays antibiotic resistance. Its presence within the sinuses of chronic rhinosinusitis sufferers is associated with poorer quality of life. Obligately lytic bacteriophages (phages) are viruses that infect, replicate within, and lyse bacteria, causing bacterial death. The aims of this study were to assess the safety and efficacy of a 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 16hours 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.

PMID:
30615845
DOI:
10.1016/j.trsl.2018.12.002
[Indexed for MEDLINE]

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