Hale Samuel J M, Wagner Mackenzie Brett, Lux Christian A, Biswas Kristi, Kim Raymond, Douglas Richard G
Department of Surgery, Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand.
Front Pharmacol. 2022 Jun 13;13:840323. doi: 10.3389/fphar.2022.840323. eCollection 2022.
The role of bacterial biofilms in chronic and recalcitrant diseases is widely appreciated, and the treatment of biofilm infection is an increasingly important area of research. Chronic rhinosinusitis (CRS) is a complex disease associated with sinonasal dysbiosis and the presence of bacterial biofilms. While most biofilm-related diseases are associated with highly persistent but relatively less severe inflammation, the presence of biofilms in CRS is associated with greater severity of inflammation and recalcitrance despite appropriate treatment. Oral antibiotics are commonly used to treat CRS but they are often ineffective, due to poor penetration of the sinonasal mucosa and the inherently antibiotic resistant nature of bacteria in biofilms. Topical non-antibiotic antibiofilm agents may prove more effective, but few such agents are available for sinonasal application. We review compounds with antibiofilm activity that may be useful for treating biofilm-associated CRS, including halogen-based compounds, quaternary ammonium compounds and derivatives, biguanides, antimicrobial peptides, chelating agents and natural products. These include preparations that are currently available and those still in development. For each compound, antibiofilm efficacy, mechanism of action, and toxicity as it relates to sinonasal application are summarised. We highlight the antibiofilm agents that we believe hold the greatest promise for the treatment of biofilm-associated CRS in order to inform future research on the management of this difficult condition.
细菌生物膜在慢性和顽固性疾病中的作用已得到广泛认可，生物膜感染的治疗是一个日益重要的研究领域。慢性鼻窦炎（CRS）是一种与鼻窦生态失调和细菌生物膜存在相关的复杂疾病。虽然大多数与生物膜相关的疾病都伴有高度持续性但相对不太严重的炎症，但CRS中生物膜的存在却与更严重的炎症和尽管经过适当治疗仍具有顽固性有关。口服抗生素常用于治疗CRS，但由于鼻窦黏膜穿透性差以及生物膜中细菌固有的抗生素耐药性，它们往往无效。局部非抗生素抗生物膜药物可能更有效，但很少有此类药物可用于鼻窦应用。我们综述了具有抗生物膜活性、可能对治疗与生物膜相关的CRS有用的化合物，包括卤素基化合物、季铵化合物及其衍生物、双胍类、抗菌肽、螯合剂和天然产物。这些包括目前可用的制剂和仍在研发中的制剂。对于每种化合物，总结了其抗生物膜功效、作用机制以及与鼻窦应用相关的毒性。我们重点介绍了我们认为对治疗与生物膜相关的CRS最有前景的抗生物膜药物，以便为未来对这种疑难病症的管理研究提供参考。
