Novel strategies for inhibition of bacterial biofilm in chronic rhinosinusitis.

An important role has been recently reported for bacterial biofilm in the pathophysiology of chronic diseases, such as chronic rhinosinusitis (CRS). CRS, affecting sinonasal mucosa, is a persistent inflammatory condition with a high prevalence around the world. Although the exact pathological mechanism of this disease has not been elicited yet, biofilm formation is known to lead to a more significant symptom burden and major objective clinical indicators. The high prevalence of multidrug-resistant bacteria has severely restricted the application of antibiotics in recent years. Furthermore, systemic antibiotic therapy, on top of its insufficient concentration to eradicate bacteria in the sinonasal biofilm, often causes toxicity, antibiotic resistance, and an effect on the natural microbiota, in patients. Thus, coming up with alternative therapeutic options instead of systemic antibiotic therapy is emphasized in the treatment of bacterial biofilm in CRS patients. The use of topical antibiotic therapy and antibiotic eluting sinus stents that induce higher antibiotic concentration, and decrease side effects could be helpful. Besides, recent research recognized that various natural products, nitric oxide, and bacteriophage therapy, in addition to the hindered biofilm formation, could degrade the established bacterial biofilm. However, despite these improvements, new antibacterial agents and CRS biofilm interactions are complicated and need extensive research. Finally, most studies were performed in vitro, and more preclinical animal models and human studies are required to confirm the collected data. The present review is specifically discussing potential therapeutic strategies for the treatment of bacterial biofilm in CRS patients.

An overview of possible pathogenesis mechanisms of Alternaria alternata in chronic rhinosinusitis and nasal polyposis.

Chronic Rhinosinusitis (CRS) is a multifactorial disease, and different etiologies like metabolism and immunity disorders, bacterial superantigens, biofilms, and fungal allergens are known to develop this disease, especially the CRS with nasal polyps. Alternaria alternata (Alternaria) is one of the most prevalent airborne fungal species in the nasal discharge, which might have vigorous immunologic activities in nasal epithelial cells and play an essential role in the pathogenesis of CRS. Moreover, the interaction between this fungus and the innate and adaptive immune systems leads to the development of chronic inflammation. This inflammation may consequently instigate the CRS and nasal polyposis. The attenuation of surfactant protein synthesis or intracellular reserves and mucus hypersecretion could prevent the clearance of Alternaria from sinuses and may be correlated with colonization and re-infection of airborne fungi. Furthermore, higher expression of cathelicidin, thymic stromal lymphopoietin, toll-like receptors, and T helper 2-dominant immune responses can result in an IgE-mediated pathway activation and eosinophils degranulation. Moreover, higher local Alternaria-specific IgE was shown to be correlated with eosinophilic cationic proteins and might relate to nasal polyps. However, the role of genetic and environmental factors affecting CRS and nasal polyposis is not well studied. Likewise, further animal and clinical studies are required to better understand the role of Alternaria in CRS disease. The current article reviews the recent findings around the Alternaria-induced CRS and nasal polyposis.

Bacteriophage therapy for inhibition of multi drug-resistant uropathogenic bacteria: a narrative review.

Multi-Drug Resistant (MDR) uropathogenic bacteria have increased in number in recent years and the development of new treatment options for the corresponding infections has become a major challenge in the field of medicine. In this respect, recent studies have proposed bacteriophage (phage) therapy as a potential alternative against MDR Urinary Tract Infections (UTI) because the resistance mechanism of phages differs from that of antibiotics and few side effects have been reported for them. Escherichia coli, Klebsiella pneumoniae, and Proteus mirabilis are the most common uropathogenic bacteria against which phage therapy has been used. Phages, in addition to lysing bacterial pathogens, can prevent the formation of biofilms. Besides, by inducing or producing polysaccharide depolymerase, phages can easily penetrate into deeper layers of the biofilm and degrade it. Notably, phage therapy has shown good results in inhibiting multiple-species biofilm and this may be an efficient weapon against catheter-associated UTI. However, the narrow range of hosts limits the use of phage therapy. Therefore, the use of phage cocktail and combination therapy can form a highly attractive strategy. However, despite the positive use of these treatments, various studies have reported phage-resistant strains, indicating that phage-host interactions are more complicated and need further research. Furthermore, these investigations are limited and further clinical trials are required to make this treatment widely available for human use. This review highlights phage therapy in the context of treating UTIs and the specific considerations for this application.