Drilling Amanda, Morales Sandra, Boase Samuel, Jervis-Bardy Joshua, James Craig, Jardeleza Camille, Tan Neil Cheng-Wen, Cleland Edward, Speck Peter, Vreugde Sarah, Wormald Peter-John
Department of Surgery-Otolaryngology Head and Neck Surgery, University of Adelaide, Adelaide, SA, Australia.
Int Forum Allergy Rhinol. 2014 Mar;4(3):176-86. doi: 10.1002/alr.21270. Epub 2014 Jan 21.
Treatment of sinonasal bacterial biofilms continues to be a challenge in modern rhinology. This study's objective was to assess the safety and efficacy of topically applied Cocktail of S. aureus specific phage (CTSA) alone and in combination with ethylenediaminetetraacetic acid (EDTA) for treatment of Staphylococcus aureus biofilms in vivo.
Using a sheep model of sinusitis, frontal sinuses (n = 6 per treatment) were flushed once daily with a CTSA (2 × 10(6) plaque forming units [PFU]/mL), with or without EDTA (0.075 mg/mL), and compared to a control flush containing saline and heat-inactivated CTSA. Safety was assessed using histology and scanning electron microscopy (SEM) after treatment for 3 days. Efficacy was assessed by quantifying the generation of S. aureus biofilms in the frontal sinuses after 5 days of treatment. Biofilm mass was compared between treatment groups and controls using LIVE/DEAD BacLight staining and confocal scanning laser microscopy to visualize the tissue sections. COMSTAT2 software was used to compute the biofilm mass present on tissue sections.
Tissue morphology was conserved, with no significant signs of inflammation, when comparing control and test treatments. Furthermore, SEM analysis indicated test treatments were not toxic or damaging to mucosal cilia. COMSTAT2 quantification of biofilm showed a significant reduction in biofilm levels when comparing the control with CTSA (p = 0.0043), EDTA (p = 0.0095), and CTSA-EDTA (p = 0.0022) treatments.
Results indicate that CTSA and EDTA are safe and efficacious for short-term topical application against S. aureus infection in a sheep sinusitis model, and have the potential to be translated to a clinical setting.
在现代鼻科学中，鼻窦细菌生物膜的治疗仍然是一项挑战。本研究的目的是评估局部应用金黄色葡萄球菌特异性噬菌体鸡尾酒（CTSA）单独以及与乙二胺四乙酸（EDTA）联合用于体内治疗金黄色葡萄球菌生物膜的安全性和有效性。
使用绵羊鼻窦炎模型，每天一次用CTSA（2×10⁶噬菌斑形成单位[PFU]/mL）冲洗额窦（每组治疗n = 6），添加或不添加EDTA（0.075 mg/mL），并与含有生理盐水和热灭活CTSA的对照冲洗液进行比较。治疗3天后，使用组织学和扫描电子显微镜（SEM）评估安全性。治疗5天后，通过量化额窦中金黄色葡萄球菌生物膜的生成来评估疗效。使用LIVE/DEAD BacLight染色和共聚焦扫描激光显微镜观察组织切片，比较治疗组和对照组之间的生物膜质量。使用COMSTAT2软件计算组织切片上存在的生物膜质量。
比较对照和试验治疗时，组织形态保持不变，无明显炎症迹象。此外，SEM分析表明试验治疗对粘膜纤毛无毒或无损害。生物膜的COMSTAT2定量显示，将对照组与CTSA（p = 0.0043）、EDTA（p = 0.0095）和CTSA-EDTA（p = 0.0022）治疗组进行比较时，生物膜水平显著降低。
结果表明，在绵羊鼻窦炎模型中，CTSA和EDTA短期局部应用对金黄色葡萄球菌感染是安全有效的，并且有可能转化到临床应用中。
