Drilling Amanda J, Ooi Mian L, Miljkovic Dijana, James Craig, Speck Peter, Vreugde Sarah, Clark Jason, Wormald Peter-John
Department of Surgery-Otolaryngology Head and Neck Surgery, The University of Adelaide Adelaide, SA, Australia.
Adelaide Pathology Partners Adelaide, SA, Australia.
Front Cell Infect Microbiol. 2017 Feb 24;7:49. doi: 10.3389/fcimb.2017.00049. eCollection 2017.
biofilms contribute negatively to a number of chronic conditions, including chronic rhinosinusitis (CRS). With the inherent tolerance of biofilm-bound bacteria to antibiotics and the global problem of bacterial antibiotic resistance, the need to develop novel therapeutics is paramount. Phage therapy has previously shown promise in treating sinonasal biofilms. This study investigates the long term (20 days) safety of topical sinonasal flushes with bacteriophage suspensions. The bacteriophage cocktail NOV012 against selected for this work contains two highly characterized and different phages, P68 and K710. Host range was assessed against strains isolated from CRS patients using agar spot tests. NOV012 was applied topically to the frontal sinus region of sheep, twice daily for 20 days. General sheep wellbeing, mucosal structural changes and inflammatory load were assessed to determine safety of NOV012 application. NOV012 could lyse 52/61 (85%) of a panel of locally derived CRS clinical isolates. Application of NOV012 to the frontal sinuses of sheep for 20 days was found to be safe, with no observed inflammatory infiltration or tissue damage within the sinus mucosa. NOV012 cocktail appears safe to apply for extended periods to sheep sinuses and it could infect and lyse a wide range of CRS clinical isolates. This indicates that phage therapy has strong potential as a treatment for chronic bacterial rhinosinusitis.
生物膜对包括慢性鼻-鼻窦炎（CRS）在内的多种慢性疾病产生负面影响。鉴于生物膜包裹的细菌对抗生素具有内在耐受性以及细菌抗生素耐药性这一全球性问题，开发新型治疗方法至关重要。噬菌体疗法此前已显示出治疗鼻窦生物膜的前景。本研究调查了用噬菌体悬浮液进行鼻腔局部冲洗20天的长期安全性。针对这项工作选择的噬菌体鸡尾酒NOV012包含两种高度特征化且不同的噬菌体，P68和K710。使用琼脂斑点试验评估了对从CRS患者分离出的菌株的宿主范围。将NOV012局部应用于绵羊的额窦区域，每天两次，持续20天。评估绵羊的总体健康状况、黏膜结构变化和炎症负荷，以确定应用NOV012的安全性。NOV012能够裂解一组本地来源的CRS临床分离株中的52/61（85%）。发现将NOV012应用于绵羊额窦20天是安全的，在鼻窦黏膜内未观察到炎症浸润或组织损伤。NOV012鸡尾酒似乎可以长期安全地应用于绵羊鼻窦，并且它可以感染并裂解多种CRS临床分离株。这表明噬菌体疗法作为慢性细菌性鼻-鼻窦炎的治疗方法具有强大的潜力。
