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.

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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 multidrugresistant 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. K E Y W O R D S antibiofilm agents, bacterial biofilm, chronic rhinosinusitis, multi-drug resistant bacteria, new therapeutic approaches Phospholipid liposomes Reducing the liposome size and formulating liposomes as positively charged increased the penetration and inhibition of bacterial biofilms Dong et al. (2015) 2017 S. epidermidis Gentamicin with laser generated shockwaves (LGS) LGS increases the efficacy of topical antibiotics in an in vitro model Yao et al. (2017) 2017 S. aureus Silk fibroin-nano silver The Nanoparticle solution was an effective topical agent against S. aureus biofilms in the rabbit model of sinusitis Jia et al. (2017) 2018 Prospective blinded comparative study Spray cryotherapy Spray cryotherapy removed multi-species biofilm from the mucosa surface Vlad et al. (2018) 2018 S. aureus Chitogel combined with deferiprone and gallium protoporphyrin (CG-DG) CG-DG was effective against S. aureus biofilms in a sheep sinusitis model Ooi et al. (2018) 2020 Haemophilus influenzae (CIs) Antibodies against the DNABII protein integration host factor This treatment was highly effective in preventing the formation H. influenzae biofilms Martyn et al. (2020) 2020 S. aureus Isosorbide mononitrate (ISMN) loaded nanoparticles conjugated with an anti-S. aureus alpha-toxin antibody This trea...