Department of Surgery - Otolaryngology Head and Neck Surgery, The Queen Elizabeth Hospital, University of Adelaide, Woodville South, South Australia, Australia.
Adelaide Medical School, University of Adelaide, Adelaide, South Australia, Australia.
Transl Res. 2019 Apr;206:41-56. doi: 10.1016/j.trsl.2018.12.002. Epub 2018 Dec 19.
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 10-10 PFU/mL. No safety concerns were noted.
铜绿假单胞菌（PA）是一种经常表现出抗生素耐药性的细菌病原体。它存在于慢性鼻窦炎患者的鼻窦中，与生活质量较差有关。专性裂解噬菌体（噬菌体）是感染、在细菌内部复制并裂解细菌，导致细菌死亡的病毒。本研究的目的是评估 CT-PA 在绵羊鼻窦炎模型中的安全性和疗效。绵羊鼻窦炎模型经过改编，以模拟 PA 在绵羊额窦中的感染。为了评估疗效，在 7 天生物膜形成期后，绵羊接受了为期 1 周的每日两次额窦环钻冲洗 CT-PA 或生理盐水。使用 LIVE/DEAD BacLight 染色对额窦黏膜上的生物膜进行定量。为了评估安全性，绵羊接受了为期 3 周的每日两次额窦环钻冲洗 CT-PA 或载体对照。在整个治疗过程中采集血液和粪便样本。对额窦、肺、心脏、肝脏、脾脏和肾脏组织进行组织病理学检查。使用扫描电子显微镜（SEM）观察鼻窦纤毛。疗效组显示所有测试浓度的 CT-PA 均能显著降低生物膜生物量（P < 0.05）。噬菌体在鼻窦中的存在至少在最后一次冲洗后 16 小时内得以维持。所有安全组绵羊均完成了 3 周的治疗。噬菌体在粪便中持续存在，在血液和器官样本中偶尔存在。组织学和 SEM 显示没有与治疗相关的损伤。总之，CT-PA 能够在 10-10 PFU/mL 的浓度下降低鼻窦 PA 生物膜。未发现安全问题。
