Comparison of sinus distribution between nasal irrigation and nasal spray using fluorescein-labelled in patients with chronic rhinosinusitis: A randomised clinical trial.

OBJECTIVE: This study aims to compare the potential sinus distribution between high-volume nasal irrigation and nasal spray in chronic rhinosinusitis (CRS) patients who have not undergone sinus surgery. DESIGN AND SETTING: A randomised clinical study was conducted at the Otolaryngology-Head & Neck Surgery Department, Ramathibodi Hospital, Faculty of Medicine, Mahidol University. PARTICIPANTS: Forty patients undergoing endoscopic sinus surgery (ESS) for CRS. Thirty-eight patients met the inclusion criteria and were randomly assigned to receive nasal irrigation or nasal spray mixed with fluorescein sodium preoperatively. MAIN OUTCOME MEASURES: The primary outcome was the mean difference in the staining score of fluorescein in all sinuses between the two groups. RESULTS: The total fluorescein staining score for all sinuses in the nasal irrigation group was significantly higher than the score from the nasal spray group, with a mean difference score of 2.90, 95% confidence interval: 1.22-4.58, p = .001. The most significantly affected sinuses were the maxillary and the anterior ethmoid sinuses, while the frontal and sphenoid sinuses had only minimal staining from both techniques. CONCLUSION: Nasal irrigation is a potential route to deliver drugs into the sinus in unoperated CRS patients. However, it is not considered a superior method to nasal spray in the most challenging anatomical areas, that is, the frontal and sphenoid sinuses.

A methodological pipeline for the preclinical evaluation of novel topical agents for the treatment of CRS.

KEY POINTS: Novel topical therapeutics require extensive pre-clinical testing to assess efficacy and safety. Antibiofilm or immunosuppressant agents can utilize ex vivo models to measure ciliotoxicity. Agents that are found to be effective and non-toxic ex vivo warrant further investigation in vivo.

Double blind randomized controlled trial measuring the efficacy of nebulized steroid at half dose in comparison to high volume squeeze bottle steroid irrigation in management of patients with chronic rhinosinusitis.

KEY POINTS: Nebulized budesonide is effective at half dose compared to budesonide irrigation in CRS. Nasal nebulizers provide an alternative for delivery of topical steroids to the sinuses.

Upper airway microbiome transplantation for patients with chronic rhinosinusitis.

BACKGROUND: Chronic or recurrent rhinosinusitis without polyps (CRSsNP) is characterized by a persistent inflammation of the sinonasal mucosa. The underlying cause is unclear but increasing interest has been directed toward changes in the sinonasal microbiome as a potential driver. METHODS: Twenty-two patients diagnosed with CRSsNP were treated with antibiotics for 13 days, followed by 5 consecutive days of nasal microbiome transplants from healthy donors. Outcome measures were 22-item Sino-Nasal Outcome Test (SNOT-22) questionnaire, total nasal symptom score (TNSS), endoscopic grading, 16S ribosomal RNA (rRNA) next generation sequencing (microbiome analysis), and nasal lavage fluid analysis of inflammatory cytokines. Patients were examined at the start of the study and after antibiotic treatment as well as 10 days and 3 months after the transplant series. RESULTS: At the end of the study, patients reported significantly reduced SNOT-22 scores and microbiome analysis showed significantly increased abundance and diversity. No significant change was observed for TNSS or endoscopic scoring. CONCLUSION: Nasal microbiome transplants obtained from healthy individuals and administered as nasal lavages to patients with CRSsNP are feasible. The patients reported significant and lasting reduction of symptoms and these findings were associated with a lasting increase in abundance and diversity of the local bacterial flora. The observations, which need to be confirmed by randomized controlled trials, may constitute a new treatment avenue for these difficult to treat patients where antibiotics only provide short lasting symptom control.

Efficacy of the exhalation delivery system with fluticasone in patients with chronic rhinosinusitis with nasal polyps whose symptoms recur after sinus surgery.

BACKGROUND: Sinus surgery removes inflamed tissue, restores airflow, and improves delivery of medication into surgically opened spaces. The exhalation delivery system with fluticasone (EDS-FLU; XHANCE® ) uses a novel delivery system to create closed-palate, positive-pressure, bidirectional mechanics that significantly alter the deposition of the topically acting anti-inflammatory medication. We ask whether EDS-FLU efficacy differs for patients with recurrent symptoms after sinus surgery versus patients without surgery. OBJECTIVE: We aimed to compare EDS-FLU treatment responses in patients with recurrent symptoms after endoscopic sinus surgery (ESS) and patients who have never had sinus surgery. METHODS: Data were pooled from two large, controlled trials (NAVIGATE I and II) for exploratory analyses. Chronic rhinosinusitis symptoms, polyp grade, and quality-of-life measures were compared between patients with prior ESS and those without prior ESS. RESULTS: Patients with prior ESS (exhalation delivery system-placebo [n = 53], EDS-FLU 186 µg [n = 52], and EDS-FLU 372 µg [n = 49]) and unoperated patients (exhalation delivery system-placebo [n = 108], EDS-FLU 186 µg [n = 108], and EDS-FLU 372 µg [n = 111]) treated with EDS-FLU reported similar and substantial benefits as measured by multiple symptom and quality-of-life/functioning outcomes (congestion score, 22-Item Sinonasal Outcomes Test [SNOT-22], Rhinosinusitis Disability Index [RSDI], Patient Global Impression of Change) and by nasal polyp grade. In previously operated patients, unlike surgery-naive patients, multiple outcomes (SNOT-22, RSDI, polyp grade) consistently showed numerically but not statistically greater responses to the higher dose. CONCLUSIONS: Patients with recurrent symptoms after sinus surgery who were treated with EDS-FLU demonstrated significant symptom and quality-of-life improvement. Unlike unoperated patients, patients with prior ESS had a numerically but not statistically greater response to the higher dose of EDS-FLU (two sprays per nostril twice a day).

Pharmacokinetic-based failure of a detergent virucidal for severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) nasal infections: A preclinical study and randomized controlled trial.

BACKGROUND: The nose is the portal for severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infection, suggesting the nose as a target for topical antiviral therapies. The purpose of this study was to assess both the in vivo and in vitro efficacy of a detergent-based virucidal agent, Johnson and Johnson's Baby Shampoo (J&J), in SARS-CoV-2-infected subjects. METHODS: Subjects were randomized into three treatment groups: (1) twice daily nasal irrigation with J&J in hypertonic saline, (2) hypertonic saline alone, and (3) no intervention. Complementary in vitro experiments were performed in cultured human nasal epithelia. The primary outcome measure in the clinical trial was change in SARS-CoV-2 viral load over 21 days. Secondary outcomes included symptom scores and change in daily temperature. Outcome measures for in vitro studies included change in viral titers. RESULTS: Seventy-two subjects completed the clinical study (n = 24 per group). Despite demonstrated safety and robust efficacy in in vitro virucidal assays, J&J irrigations had no impact on viral titers or symptom scores in treated subjects relative to controls. Similar findings were observed administering J&J to infected cultured human airway epithelia using protocols mimicking the clinical trial regimen. Additional studies of cultured human nasal epithelia demonstrated that lack of efficacy reflected pharmacokinetic failure, with the most virucidal J&J detergent components rapidly absorbed from nasal surfaces. CONCLUSION: In this randomized clinical trial of subjects with SARS-CoV-2 infection, a topical detergent-based virucidal agent had no effect on viral load or symptom scores. Complementary in vitro studies confirmed a lack of efficacy, reflective of pharmacokinetic failure and rapid absorption from nasal surfaces.

Chitogel following endoscopic sinus surgery promotes a healthy microbiome and reduces postoperative infections.

BACKGROUND: Postoperative infections following endoscopic sinus surgery (ESS) impair wound healing and lead to poor outcomes. The aim of this study is to assess the effectiveness of Chitogel to reduce postoperative infections and restore a healthy microbiome following ESS. METHODS: In this double-blinded randomized control trial, 25 patients undergoing ESS were prospectively recruited. At the end of surgery, patients were randomized to receive Chitogel to one side of the sinuses (allowing the other side to serve as control). Patients underwent routine follow-up with nasoendoscopies performed at 2, 6, and 12 weeks postoperatively. Sinus ostial measurements, microbiology, and microbiome swabs from bilateral sides were collected intraoperatively and at 12 weeks postoperatively. Additional swabs were collected if infection was present. RESULTS: Improved endoscopic appearance of the sinuses (p = 0.03) and ostial patency were noted on the Chitogel side compared with control at 12 weeks (p < 0.001). A significant decrease in infections on the Chitogel side (12.0%) compared with control (52.0%) (p = 0.005) was evident. Following the use of Chitogel, there was a significant increase in the combined relative abundance of commensals Corynebacterium and Cutibacterium (Propionibacterium) from 30.15% at baseline to 46.62% at 12 weeks compared with control (47.18% to 40.79%) (p.adj = 0.01). CONCLUSION: Chitogel significantly improved both the nasoendoscopic appearance of the sinuses and sinus ostial patency at 12 weeks postoperatively. Chitogel used following ESS helps restore an improved microbiome resulting in an increase in the relative abundance of commensals Corynebacterium and Cutibacterium (Propionibacterium). A significant decrease in postoperative infections was noted following use of Chitogel.

The management of cystic fibrosis chronic rhinosinusitis: An evidenced-based review with recommendations.

BACKGROUND: Cystic fibrosis (CF) chronic rhinosinusitis (CRS) has emerged as a distinct diagnostic entity, unique from other endotypes of CRS in its presentation, pathophysiology, diagnosis, treatment, and outcomes. As the sinonasal health of this patient population may have broad effects on pulmonary health and quality of life, a comprehensive understanding of the diagnostic and therapeutic approach to CF CRS is essential. In recognizing recent scientific advances and unique treatment modalities specific to this challenging patient population, in this review we systematically evaluate the scientific literature and provide an evidenced-based review with recommendations (EBRR) for fundamental management principles of CF CRS. METHODS: A systematic review of the literature was performed. Studies evaluating interventions for the management of CF CRS were included. An iterative review process was implemented in accordance with EBRR guidelines. A treatment recommendation was generated based on an assessment of the benefits, harms, and the overall grade of evidence. RESULTS: We evaluated the published literature on 5 unique topics. Each of the following therapeutic categories was investigated explicitly for treatment outcomes in patients with CF CRS: (1) nasal saline; (2) intranasal corticosteroids (INCS); (3) topical antibiotics; (4) cystic fibrosis transmembrane conductance regulator (CFTR) modulator therapy; and (5) endoscopic sinus surgery (ESS). CONCLUSION: Based on the currently available evidence, nasal saline, ESS, and CFTR modulators are recommended in the management of CF CRS when appropriate. INCS and topical antibiotics are options. Clinical judgment and experience are essential in caring for patients with this uniquely challenging disorder.

Endoscopic outcomes in patients with AERD treated with topical antibiotics and intranasal corticosteroids.

Background: Identifying effective therapy for recalcitrant chronic rhinosinusitis with nasal polyposis (CRSwNP) is a major challenge; and subtypes such as aspirin-exacerbated respiratory disease (AERD) are even more difficult to treat. Evidence on topical antibiotics use in (CRSwNP) is lacking. Current consensus guidelines recommend against its routine use, but recent reviews show some benefit when managing recalcitrant disease after endoscopic sinus surgery (ESS). Objective: Evaluate the effect of culture-directed topical antibiotics on sinonasal outcomes in AERD patients with a positive perioperative sinonasal bacterial culture who have undergone ESS. Methods: A retrospective cohort study of AERD patients with positive sinonasal culture, who underwent ESS from 2016 to 2021 was performed. Forty-four patients were identified and stratified based on their postoperative medical treatment. Twenty-six underwent postoperative intranasal corticosteroids (INCS) alone, while eighteen underwent INCS plus a 4-weeks treatment with topical antibiotics. SNOT-22 and Lund-Kennedy score (LKS) were assessed preoperatively and at 4-weeks and 4-6 months after ESS. Results: A statistically significant improvement in the 4-weeks and 4-6 months postoperative SNOT-22 and LKS were noted within both groups (p<0.05). However, only a statistically significant difference was found in the 4-weeks postoperative LKS when comparing between treatment groups (p=0.01). Our linear regression model demonstrated a relationship between the use of combined therapy with INCS and topical antibiotics and the LKS 4-weeks post ESS (p=0.015). Conclusion: In AERD patients with a confirmed sinus infection, the combination of culture-directed topical antibiotics and intranasal corticosteroid irrigations in the postoperative period can provide a short-term improvement in endoscopic scores.

Efficacy of the exhalation delivery system with fluticasone in patients who remain symptomatic on standard nasal steroid sprays.

BACKGROUND: Standard nasal steroid sprays are often first-line treatment for chronic rhinosinusitis (CRS), but many patients remain symptomatic despite their use. The exhalation delivery system with fluticasone (EDS-FLU) has been shown to be efficacious in mixed populations of symptomatic patients, but the question remains whether benefits would be similar in those already on traditional steroid sprays. The goal of this study was to compare EDS-FLU treatment outcomes in patients who have previously failed nasal steroids. METHODS: Using pooled data from the NAVIGATE I and II trials, EDS-FLU efficacy was compared in the subgroup treated with a conventional nasal steroid at trial entry (mean duration, ≈3 years) to efficacy in the overall study population. Sensitivity analyses were performed for more restrictive definitions of the subgroup changing from prior standard nasal steroids. RESULTS: Of 482 total subjects, 218 (45.2%) reported using standard nasal steroid sprays at entry (mean duration, 1051 days). Across multiple outcome measures, improvements for "switchers" receiving EDS-FLU (least squares mean change from baseline vs EDS plus placebo) were comparable with improvements in the overall population. For EDS-FLU 372 µg, comparable improvements were observed in congestion (-0.73 vs -0.62), rhinorrhea (-0.71 vs -0.57), facial pain/pressure (-0.48 vs -0.41), and sense of smell (-0.35 vs -0.30) at week 4 and 22-item Sino-Nasal Outcome Test (-21.01 vs -20.52), Patient Global Impression of Change, and other outcomes at week 16. Results for EDS-FLU 186 µg were similar. CONCLUSION: EDS-FLU comparably improves symptoms, irrespective of whether patients are symptomatic while using conventional nasal steroids before treatment.

Novel nitric oxide-generating platform using manuka honey as an anti-biofilm strategy in chronic rhinosinusitis.

BACKGROUND: Bacterial biofilms are implicated in the pathogenesis of chronic rhinosinusitis. Nitric oxide (NO) is a key immune effector with potent antimicrobial effects, but a short half-life limits achievement of therapeutic concentrations. We hypothesized that manuka honey (MH) could induce sustained reduction of nitrite to NO causing biofilm disruption and that this effect would be enhanced with the addition of a NO-releasing microparticle. METHODS: Porous organosilica microparticles containing nitrosylated thiol groups were formulated (SNO-MP). MH was combined with serial dilutions of nitrite. NO release was evaluated using a NO analyzer. The susceptibility of 2 strains of Pseudomonas aeruginosa biofilms to these NO-releasing platforms was evaluated using confocal microscopy. Cell viability and biofilm volume were quantified. Statistical analysis was performed using the Mann-Whitney U test with SPSS software. RESULTS: MH with nitrite generated a linear increase in NO formation. SNO-MP induced a bolus release of NO within 5 minutes, followed by a sustained plateau phase. MH with nitrite combined with SNO-MP enhanced NO release during the plateau phase. MH with nitrite reduced biofilm live cells and volume by 88.5% to 96.9% and 95.1% to 95.6%, respectively, vs control (p < 0.0001). SNO-MP reduced live cells and volume by 61.0% to 98.5% and 74.7% to 85.7%, respectively, vs control (p < 0.0001). MH with nitrite combined with SNO-MP nearly eradicated biofilm, with a 98.3% to 99.8% (log 1.8-2.6) reduction in viability and a 91.4% to 97.7% decrease in volume (p < 0.0001 vs control). CONCLUSION: A novel platform that generates NO using MH and nitrite produces a potent anti-biofilm effect, which can be further enhanced with the addition of SNO-MP.

Effects of povidone-iodine composite on the elimination of bacterial biofilm.

BACKGROUND: Povidone-iodine (PVP-I) is well known as an antiseptic and exhibits extensive activity against various pathogens. However, due to its uniquely unpleasant nature, it cannot be used locally to deactivate various sinonasal pathogens. Therefore, we developed a PVP-I composite that blocks the unpleasant odor of PVP-I for use as a local antiseptic in the sinonasal cavity and evaluated its effect on bacterial biofilm's formation and elimination in in vivo and in vitro models. METHODS: MTT, lactate dehydrogenase, and live/dead staining assay were performed to examine the cellular toxicity of PVP-I composites on the primary human nasal epithelial and RPMI 2650 cells. Crystal violet assay was performed to quantify bacterial biofilm after treating with various agents, including PVP-I and antibiotics. Hematoxylin-and-eosin staining, live/dead staining assay, and scanning electron microscopy were conducted to evaluate the effect of PVP-I on biofilm formation in a mice biofilm model. RESULTS: It was observed that the PVP-I composite did not have any significant toxic effect on the nasal epithelial cells. Furthermore, the PVP-I composite effectively inhibited the formation of bacterial biomass within a dose-dependent manner after 48 hours of incubation with Pseudomonas aeruginosa and Staphylococcus aureus. In mice, it effectively eliminated biofilm from the mucosa of the nasal cavity and maxillary sinus at the tested concentrations. CONCLUSION: The results of this study indicate that the PVP-I composite is a promising compound that could be used locally to prevent the formation of biofilms and to eliminate them from the sinonasal cavity.

Concordance of self-reported practice patterns of American Rhinologic Society members with the International Consensus Statement of Allergy and Rhinology: Rhinosinusitis.

BACKGROUND: The 2016 International Consensus Statement on Allergy and Rhinology: Rhinosinusitis (ICAR:RS) is a collaborative distillation of available research and consensus recommendations for the management for chronic rhinosinusitis (CRS). However, implementation of the ICAR:RS recommendations in the reality of clinical practice is not clearly defined. METHODS: An anonymous, web-based survey of the American Rhinologic Society membership was performed in October, 2018. Respondents were asked about the frequency that they recommended the various treatments reviewed in ICAR:RS in the context of medical management for CRS. A 7-point Likert-type scale assessed the frequency of treatment patterns. RESULTS: A total of 140 members completed the survey (response rate 11.9%). Seventy-two (51.4%) were in practice for 0 to 15 years, 61 (43.6%) completed a rhinology fellowship, and 73 (52.1%) worked in private practice. Disparate treatment patterns were reported for each of the therapies assessed for CRS, including those that were "recommended" or "recommended against" in ICAR:RS. Members with <15 years of experience were more likely to use nasal saline irrigation. Fellowship-trained respondents reported a greater likelihood of using nasal saline irrigation and aspirin desensitization (for patients with aspirin-exacerbated respiratory disease). Practitioners in academic medicine were more likely to utilize aspirin desensitization than those in private practice. Surgeons performing >100 sinus surgeries per year were more likely to use topical antibiotics. CONCLUSION: The range of reported treatment patterns identified in this study despite the availability of the ICAR:RS recommendations may suggest the need for improved standardization of CRS management.

Guidance for contemporary use of biologics in management of chronic rhinosinusitis with nasal polyps: discussion from a National Institutes of Health-sponsored workshop.

BACKGROUND: Biologic medications are emerging as options for treating chronic rhinosinusitis with nasal polyps (CRSwNP). Several questions remain regarding patient selection, indications, clinical efficacy, and cost effectiveness. METHODS: In November 2019, a group of physicians and scientists gathered to consider strategies for future studies regarding biologics. During the discussion, gaps in knowledge highlighted a need for a consensus on the present day use of biologics in polyp patients. RESULTS: The goal of this guideline is to propose recommendations for the current use of biologics in CRSwNP as new evidence continues to emerge and inform practice. CONCLUSION: We suggest that physicians evaluate patients on an individual basis and closely monitor for improvement due to the high cost and unknown long-term effects of biologics.

Topical antibiotic therapy in chronic rhinosinusitis: an update.

BACKGROUND: Topical antibiotic therapies have been investigated for their use in chronic rhinosinusitis (CRS). However, society guidelines and evidence-based medicine reviews have recommended against the use of topical antibiotic therapy based on randomized controlled trials (RCTs). The purpose of this article is to review recent clinical research published since the aforementioned guidelines were published. METHODS: A structured literature review was performed on clinical studies published in the last 5 years investigating the use of topical antibiotic therapies. RESULTS: One double-blinded, randomized controlled trial (DB-RCT) supported the use of tobramycin using a vibrating aerosolizer; 1 non-blinded non-randomized controlled prospective trial lent support to use of topical ofloxacin for its anti-biofilm properties; and 1 meta-analysis found mupirocin irrigations to be beneficial in the short term. One Cochrane Review was unable to make a recommendation as no trial met the inclusion criteria. An additional systematic review found limited evidence to support the use of topical antibiotics with the exception of mupirocin irrigations that may be considered in Staphylococcus aureus infections. Two retrospective studies found that topical antibiotics change bacterial cultures of the sinuses. CONCLUSION: There is additional evidence to support continuing investigation of topical antibiotic therapies. Further, larger RCTs are required to establish the efficacy of topical antibiotic therapies.

Head and Bottle Angles Achieved by Patients During High-Volume Sinonasal Irrigations.

BACKGROUND: Certain head positions can optimize topical irrigation distribution to specific sinuses. No studies have assessed whether patients attain these positions when irrigating. OBJECTIVE: The purpose of this study was to assess head and bottle angles achieved when patients irrigate based on instructions from an irrigation device or from a Rhinologist. METHODS: Study approval was obtained from Henry Ford Health System's Institutional Review Board (10604). Forty-two patients with various rhinologic conditions were equally divided into groups based on irrigation instruction type: pictoral instructions from an irrigation device or written/verbal instructions from a Rhinologist. Both groups' instructions directed nose-to-floor head positioning. Simulating home irrigations, patients irrigated 120 mL of saline into each naris using 240 mL squeeze bottles. Frontal and lateral views were captured using video cameras. On frontal view, angles were measured between (1) nasal dorsum (ND) and bottle tip (BT; n = 84) and (2) ND and vertical (V; n = 84). On lateral view, angles were measured between (1) line from nasion-to-pogonion (NTP) and horizontal (H) (n = 73) and (2) NTP and BT (n = 73). RESULTS: On lateral view, average angle between NTP and H was 20.0° (standard deviation [SD] = 13.1, 95% confidence interval [CI] = 17.0-23.0) and between NTP and BT was 59.4° (SD = 15.8, 95% CI = 55.8-63.1). On frontal view, average angle between ND and V was 9.5° (SD = 19.5, 95% CI = 5.3-13.6) and between ND and BT was 24.5° (SD = 12.0, 95% CI = 21.9-27.0). There were no significant angle differences between sides or instruction types. CONCLUSION: When instructed to irrigate in the nose-to-floor head position, patients achieved a head position uprotated 20° on lateral view and vertex rotated 10° away from the side of irrigation on frontal view.

Draf IIB with superior septectomy: finding the "middle ground".

BACKGROUND: Previous studies have demonstrated a high failure rate of endoscopic sinus surgery (ESS) with Draf IIa in patients with diffuse polyposis, asthma, and aspirin-exacerbated respiratory disease. A high percentage of these patients progress to endoscopic modified Lothrop procedure (EMLP). We describe a modification of the Draf IIb with a superior septectomy (IIb+SS), which may provide similar therapeutic benefit as demonstrated by the distribution of sinus irrigations in the sinus cavity with ESS with IIb+SS vs ESS with EMLP. METHODS: ESS with IIb+SS was performed on 6 cadaver heads. Fluorescein-dyed irrigations were performed on each head and penetration was recorded using video endoscopy. EMLP was subsequently performed on each head with repeat dye-irrigation and video endoscopy. The videos were reviewed by 4 blinded fellowship-trained rhinologists, and irrigant penetration of the maxillary, ethmoid, frontal, sphenoid sinuses, and olfactory cleft was graded 0 to 3 (3 implying complete staining). RESULTS: The mean scores when comparing IIb+SS to EMLP were as follows: overall 1.99 vs 1.97 (p = 0.816), maxillary sinus 2.67 vs 2.38 (p = 0.128), ethmoid sinus 1.88 vs 1.98 (p = 0.536), sphenoid sinus 2.58 vs 2.50 (p = 0.467), frontal sinus 1.13 vs 1.38 (p = 0.073), and olfactory cleft 1.71 vs 1.63 (p = 0.529). There was no significant difference between subsites. Interrater reliability was good (Cronbach's alpha = 0.781). CONCLUSION: Performing ESS with IIb+SS provides similar irrigation delivery benefits to ESS with EMLP, without the need for altering natural sinus outflow and creating circumferential scarring. Further studies evaluating its use in patients that are high risk for revision surgery are needed.

Nitric oxide-releasing microparticles as a potent antimicrobial therapeutic against chronic rhinosinusitis bacterial isolates.

BACKGROUND: Bacteria, particularly in the biofilm state, may be implicated in the pathogenesis of chronic rhinosinusitis (CRS) and enhance antibiotic resistance. Nitric oxide (NO) is a gaseous immunomodulator with antimicrobial activity and a short half-life, complicating achievement of therapeutic concentrations. We hypothesized that a novel microparticle-based delivery platform, which allows for adjustable release of NO, could exhibit potent antibacterial effects. METHODS: Porous organosilica microparticles (SNO-MP) containing nitrosylated thiol groups were formulated. Dissociation of the nitrosothiol groups generates NO at body temperature. The susceptibility of bacterial isolates from CRS patients to SNO-MP was evaluated through a colony forming unit (CFU) assay. Serial dilutions of SNO-MP in triplicate were incubated with isolates in suspension for 6 hours followed by plating on tryptic soy agar and overnight incubation followed by CFU quantification. Statistical analysis was performed with SPSS using one-way analysis of variance with Bonferroni correction. RESULTS: SNO-MP displayed antibacterial activity against gram-positive (methicillin-resistant and -sensitive Staphylococcus aureus) and gram-negative (Pseudomonas aeruginosa, Enterobacter aerogenes, and Proteus mirabilis) isolates. SNO-MP induced dose-dependent reductions in CFU across all strains. Compared with controls and blank nanoparticles, SNO-MP (10 mg/mL) induced a 99.99%-100% reduction in CFU across all isolates, equivalent to a 5-9 log kill (p < 0.005). There was no statistically significant difference in CFU concentration between controls and blank microparticles. CONCLUSION: SNO-MP demonstrates potent bactericidal effect against antibiotic-resistant CRS bacterial strains.