Rhinosinusitis (RS) is an acute (ARS) or chronic (CRS) inflammatory disease of the nasal and paranasal sinus mucosa. CRS is a heterogeneous condition characterized by distinct inflammatory patterns (endotypes) and phenotypes associated with the presence (CRSwNP) or absence (CRSsNP) of nasal polyps. Mucosal barrier and mucociliary clearance dysfunction, inflammatory cell infiltration, mucus hypersecretion, and tissue remodeling are the hallmarks of CRS. However, the underlying factors, their priority, and the mechanisms of inflammatory responses remain unclear. Several hypotheses have been proposed that link CRS etiology and pathogenesis with host (eg, “immune barrier”) and exogenous factors (eg, bacterial/fungal pathogens, dysbiotic microbiota/biofilms, or staphylococcal superantigens). The abnormal interplay between these factors is likely central to the pathophysiology of CRS by triggering compensatory immune responses. Here, we discuss the role of the sinonasal microbiota in CRS and its biofilms in the context of mucosal zinc (Zn) deficiency, serving as a possible unifying link between five host and “bacterial” hypotheses of CRS that lead to sinus mucosa remodeling. To date, no clear correlation between sinonasal microbiota and CRS has been established. However, the predominance of Corynebacteria and Staphylococci and their interspecies relationships likely play a vital role in the formation of the CRS-associated microbiota. Zn-mediated “nutritional immunity”, exerted via calprotectin, alongside the dysregulation of Zn-dependent cellular processes, could be a crucial microbiota-shaping factor in CRS. Similar to cystic fibrosis (CF), the role of SPLUNC1-mediated regulation of mucus volume and pH in CRS has been considered. We complement the biofilms’ “mechanistic” and “mucin” hypotheses behind CRS pathogenesis with the “structural” one – associated with bacterial “corncob” structures. Finally, microbiota restoration approaches for CRS prevention and treatment are reviewed, including pre- and probiotics, as well as Nasal Microbiota Transplantation (NMT).

Vocal rehabilitation with implantation of voice prosthesis has been recognized as one of the most popular intervention for patients after total laryngectomy. The main threat to its users is leakage through the tracheo-esophageal fistula caused by prosthesis deformation and damage to the valve mechanism due to colonization with fungal or bacterial/fungal biofilms. The uniqueness of the described case represents the use of the same Provox voice prosthesis during the period of almost 10 years.

Introduction: Voice prostheses (VPs) are devices that are widely used in voice rehabilitation of patients after laryngectomy. The main cause of VPs failure is their destruction by the growth of biofilm, mainly fungal. Aim: The aim of this study was to design and build a tracheoesophageal fistula (TEF) simulator to observe and analyse the process of biofilm formation on voice prostheses and its effect on the structure of the material from which they are made, in conditions as close to real as possible. Methods: Biofilm cultures were performed on voice prostheses under controlled in vitro conditions using a TEF simulator. Then, the crystal violet staining and confocal microscopic examination were performed. Results: The analysis of voice prostheses cultured in the TEF simulator conditions confirmed the presence of biofilm on their surface. Conclusions: The TEF simulator can be a valuable tool for future studies of silicone modifications that can limit the growth of biofilm on the VPs.

Background/Objectives: Ceragenins (CSAs) maintain strong antibacterial activity even in cystic fibrosis (CF) sputum. Ivacaftor (IVA), a CF transmembrane regulator modulator, provides significant clinical benefits in CF therapy. Based on these properties, we hypothesized that the combination of CSAs and IVA, due to their antibacterial and biofilm-penetrating abilities, may also be beneficial in the treatment of chronic rhinosinusitis (CRS), including CRS in CF patients. Notably, the physicochemical properties of biofilms in chronic rhinosinusitis (CRS) resemble those in CF sputum. Methods: We determined the minimal inhibitory and bactericidal concentrations (MIC and MBC) and the fractional inhibitory concentration index (FICI) for ceragenins (CSA-13, CSA-44, CSA-131), ivacaftor (IVA), selected conventional antibiotics, and their combinations against both reference and clinical strains. Bacterial viability within biofilms was also evaluated following exposure to these agents. Atomic force microscopy (AFM) was used to analyze the morphology and nanomechanical properties of Staphylococcus aureus and Pseudomonas aeruginosa. In addition, rheological measurements of Pseudomonas aeruginosa biofilms treated with CSAs combined with IVA were performed using a rotational rheometer. Results: The tested agents demonstrated anti-biofilm activity against bacterial strains associated with CRS development. IVA enhanced the anti-biofilm effects of both CSAs and tested antibiotics. CSAs exhibited low MIC and MBC values, confirming their efficacy against tested pathogens. AFM showed that CSA-44, IVA, vancomycin, and their combinations altered the nanomechanical properties of Pseudomonas aeruginosa and Staphylococcus aureus cells. Interestingly, the addition of IVA induced aggregation of S. aureus cells. CSAs reduced the stiffness of P. aeruginosa biofilms, and co-treatment with IVA resulted in a further decrease in biofilm stiffness. Conclusions: These findings indicate that ceragenins, particularly in combination with ivacaftor, represent a promising therapeutic strategy for challenging chronic infections caused by the studied bacteria. This supports further research aimed at developing new treatment methods for CRS.