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Introduction: The recalcitrant nature of patients with acute exacerbation of chronic rhinosinusitis (AECRS) potentially involves persisting colonization of the sinonasal mucosa by bacterial biofilms. Biofilms are known to be highly resistant to antibiotics, which may trigger or maintain chronic inflammation in the sinonasal mucosa. However, little is known about the relationship between the minimum inhibitory concentration (MIC) and antibiofilm concentrations of bacteria obtained from AECRS patients. Material and Methods: Thirty bacterial strains from 25 patients with AECRS were identified and underwent MIC determination (VITEK® 2). The planktonic isolates were submitted to an in vitro formation of biofilms (Modified Calgary Biofilm Device) and determination of minimum biofilm inhibitory concentration (MBIC) and minimum biofilm eradication concentration (MBEC) for amoxicillin, amoxicillin/clavulanic acid, clarithromycin, and levofloxacin. MIC of the planktonic forms was compared with MBIC and MBEC levels, according to the breakpoints established by the Clinical Laboratory Standards Institute guidelines. Results: The main bacteria retrieved was S. aureus (60%), followed by other Gram-positive and Gram-negative bacteria in lower frequencies. 76.7% of strains formed biofilm in vitro (n=23/30). The planktonic isolates presented high rates of resistance for amoxicillin (82.6%) and clarithromycin (39.1%), and lower rates for amoxicillin/clavulanic acid (17.4%). The biofilm-forming bacteria counterparts presented higher levels of MBIC and MBEC compared to the MIC levels for amoxicillin, amoxicillin/clavulanic acid, and clarithromycin. Levofloxacin was highly effective against both planktonic and biofilm forms. Planktonic resistant forms were associated with levels of antibiofilm concentrations (MBIC and MBEC). Conclusions: Biofilm-forming bacteria from AECRS patients are prevalent, and biofilm forms are highly resistant to antibiotics compared to their planktonic counterparts. Antibiotic resistance observed in planktonic forms is a good indicator of biofilm resistance, although near 20% of susceptible planktonic bacteria can produce antibiotic tolerant biofilms. [ABSTRACT FROM AUTHOR]

Background: The pathophysiology of chronic rhinosinusitis (CRS) is still not well known due to the multifactorial etiologies involved. Bacteria play a role in the pathogenesis of CRS by various means, including biofilm adhesion, intracellular persistence, or inducing inflammation secondary to toxins. Endotoxins and exotoxins, especially Staphylococcus aureus superantigens, can produce significant immune responses in the host and are implicated in patients with CRS. The majority of animal models described for CRS revalidates the pathophysiology of acute sinusitis, ostium occlusion, or foreign body associated infection. Objectives: To evaluate an experimental model of eosinophilic CRS using prolonged exposure to bacterial toxins. The histological changes in rabbits exposed to S. aureus enterotoxin B (SEB), lipopolysaccharide (LPS), or lipoteichoic acid (LTA) were compared. Methods: After induction with ovalbumin (OVA) sensitization with subcutaneous injection for 2 weeks, rabbits underwent surgery to insert an indwelling catheter into the maxillary sinus. The sinus was irrigated with OVA 3 times weekly for 2 weeks, followed by sinus irrigation with bacterial toxin (SEB: 1 µg/mL, LPS: 100 ng/mL, or LTA: 100 ng/mL) 3 times weekly for 4 weeks. The histological changes in the treated sinus were compared with control rabbits. Results: Sinuses exposed to bacterial toxins (SEB, LPS, and LTA) produced significant mucosal thickening with infiltration of inflammatory cells, notably eosinophils. SEB was the only toxin that promoted a mixed pattern of inflammation, including eosinophilic and neutrophilic infiltration. Conclusion: Our experimental model of eosinophilic CRS in rabbits produced significant mucosal thickening and inflammation in the sinuses exposed to bacterial toxins, with histological changes analogous to what is observed in patients with CRS with nasal polyps. This model may serve as a basis for future investigation of the pathogenesis of eosinophilic CRS in relation to bacterial toxins or as a model for testing new therapeutic modalities for this disease. [ABSTRACT FROM AUTHOR]

Background: Chronic rhinosinusitis (CRS) is a common illness, yet little is known about its pathogenesis, including the role played by respiratory viruses. Methods: A transversal prospective study was conducted to analyze the seasonality of CRS using real-time polymerase chain reaction to detect respiratory virus genomes in secretions and tissue samples from patients with CRS with and without nasal polyps. Results: The frequency of viral detection was 41% (31/75). The respiratory virus most frequently detected was human rhinovirus, found in 18 patients (24%), followed by human metapneumovirus, human enterovirus, human respiratory sincicial virus, human adenovirus, human bocavirus, human coronavirus, and human influenza virus, detected in 12 (16%), five (6.6%), four (5.3%), four (5.3%), two (2.6%), two (2.6%), and one (1.3%) patient(s), respectively. Although none of the patients presented symptoms when the samples were collected, there was a peak in detection of the most prevalent virus in the autumn and winter seasons of both years, similar to the pattern that occurs in acute conditions. Conclusions: The pattern of respiratory virus seasonality found in nasal mucosa, polyps, and paranasal sinus samples in patients with CRS reinforces the possibility of asymptomatic respiratory viral infections. [ABSTRACT FROM AUTHOR]

Background: The causal factor for the perpetuation of the inflammatory process in chronic rhinosinusitis with nasal polyps (CRSwNPs) has been extensively studied. However, little is known about the influence of cell death in this disease. Thus, the molecular assessment of mechanisms involved in apoptosis might shed light on the pathogenesis of CRSwNPs. This study was designed to evaluate the gene expression of different apoptotic factors in patients with NPs compared with control patients. Methods: The mRNA expression of the apoptosis mediators caspase 3, 7, and 9 and of p53 protein was analyzed using quantitative reverse transcription-polymerase chain reaction in 25 NPs and 18 control samples. Results: We observed significantly lower expression of p53 and caspase 3 and 9 in patients with CRSwNPs compared with the controls, whereas caspase 7 expression was not significantly different from the controls. Conclusion: The reduced expression of these apoptosis factors in CRSwNPs might be related to higher proliferation and the perpetuation of inflammatory cells hindering the control of the disease. A better understanding of the possible influence of apoptosis factors on CRSwNPs could provide rationale for future therapies. [ABSTRACT FROM AUTHOR]

Background The management of acute exacerbation of chronic rhinosinusitis (AECRS) is still under debate, especially because there are no adequate studies to support a best-evidence treatment for this condition. Antibiotic use for AECRS has been recommended based on extrapolation of data from acute rhinosinusitis (ARS) or non-placebo-controlled studies. This study aimed to evaluate whether antibiotic therapy modifies the course of AECRS in a randomized, placebo-controlled study. Methods Patients with AECRS were randomized in a double-blinded manner (2:1 ratio) to receive either amoxicillin-clavulanate 875 mg/125 mg twice daily (BID) (AMX-CLAV, n = 21) or placebo capsules (n = 11) during 14 days. All patients were also treated with mometasone furoate and nasal washes with saline. Global sinonasal symptoms (Severity Symptom Assessment [SSA]), quality of life (22-item Sino-Nasal Outcome Test [SNOT-22]), nasal endoscopic score (Lund-Kennedy), and microbiological evaluation were compared to evaluate the efficacy of antibiotic therapy in AECRS. Results Despite the majority of bacteria cultured from the middle meatus swab were sensitive for AMX-CLAV (84%), both AMX-CLAV and placebo-treated groups presented the same clinical course, with no difference between groups. Both groups exhibited overall improvement of symptoms on day 14 compared to day 0 ( p < 0.01), especially the items 'nasal secretion' and 'nasal obstruction' ( p < 0.05). We also observed the same evolution of nasal endoscopic and quality of life scores between placebo and AMX-CLAV. Conclusion We concluded that AMX-CLAV for 14 days did not change the clinical course of AECRS compared with placebo. The addition of an oral antibiotic to ongoing topical intranasal steroid spray may not provide additional benefit during management of AECRS. [ABSTRACT FROM AUTHOR]

• Mometasone furoate biodegradable nanofibers show sustained release. • Electrospun nanofibers are a new approach for the treatment of chronic rhinosinusitis. • Design of experiment (DoE) optimizes the development of nanosystems for drug delivery. • Mometasone furoate nanofibers showed safety in a nasal rabbit model. Biodegradable polymeric nanofibers containing mometasone furoate can be a new approach to drug delivery to treat chronic rhinosinusitis, providing controlled steroid delivery to the sinonasal mucosa. This study aimed to develop biodegradable polymeric nanofibers and explore the safety of these fibers in an in vivo rabbit model. The nanofibers' development has been optimized using the Response Surface Methodology (RSM) obtained with Design of Experiments (DoE) with the best conditions related to the polymer concentration and proportion of solvents used in the electrospinning process. The nanofibers were prepared, operating as a determinant factor, the nanofiber formation and its diameter evaluated by Scanning Electron Microscopy (SEM). The ideal system obtained was assessed by SEM, thermogravimetric analysis (TGA), X-ray diffraction (XRD), differential scanning calorimetry (DSC), assay, and drug delivery by UHLPC validated method. The results showed that the drug is dispersed in the polymeric matrix, is stable, and showed sustained release kinetics in a bio-relevant nasal environment (Higuchi model kinetics). In vivo tests, the level of inflammation at the animals' mucosa which received the nanofiber with the mometasone furoate was lower than those that received the nanofibers without the drug (α = 0.05). Histopathology analysis showed that the polymeric nanofibers containing mometasone are safe when topically applied on the sinonasal mucosa, opening a new horizon in chronic rhinosinusitis treatment. [Display omitted] [ABSTRACT FROM AUTHOR]