Azithromycin in high‐risk, refractory chronic rhinosinusitus after endoscopic sinus surgery and corticosteroid irrigations: a double‐blind, randomized, placebo‐controlled trial

Abstract

Background Refractory chronic rhinosinusitis CRS remains a significant burden for patients o en leaving them with few therapeutic options that provide low-morbidity long-term and meaningful symptomatologic and endoscopic disease improvement Macrolides have long been thought to offer both an immunomodulatory and antimicrobial effect Our objective was to evaluate the efficacy of low-dose long-term azithromycin in a carefully selected high-risk population failing appropriate medical therapy of budesonide nasal irrigations BNIs and endoscopic sinus surgery ESS Methods A double-blind randomized placebo-controlled trial was completed in a single tertiary-care center assessing the addition of mg azithromycin times per week for weeks in adults failing ESS and high-volume BNIs Associated comorbidities as well as symptomatologic microbiologic and serologic values were systematically collected Results A total of patients were enrolled and underwent ESS followed by BNI At the-month post-ESS visit patients showed disease persistence and were randomized to azithromycin or placebo Overall azithromycin when compared with placebo did not show a statistically significant difference in disease clearance vs respectively p = although patients with disease clearance who were on azithromycin showed significantly betteritem Sino-Nasal Outcome Test score improvements than patients on placebo vs − respectively p = In a subgroup analysis excluding aspirin-exacerbated respiratory disease AERD patients azithromycin significantly improved disease clearance when compared with placebo vs respectively p = with a number needed to treat of Conclusion Low-dose azithromycin is a therapeutic option with few side effects Its use can show favorable clinical outcomes in this difficult-to-treat population especially if patients are AERD-negative © 2020 ARS-AAOA, LLC.

Utilization of Transcriptomic Profiling to Identify Molecular Markers Predicting Successful Recovery Following Endoscopic Sinus Surgery for Chronic Rhinosinusitis

“…At the 4‐month time point, 59 patients (50%) attained optimal outcomes, while 59 patients (50%) showed persistence of disease and was deemed nonresponsive to ESS. Patients included needed at least 1 of the following criteria used to qualify them at high risk of disease recurrence: history of previous sinus surgery; sinus surgery at ≤38 years of age; absolute eosinophilia ≥500 cells/mm; total serum immunoglobulin E levels ≥150 kIU/L; sinus culture of a Gram‐negative organism at any time‐point; and intraoperative finding of eosinophilic mucin 11 …”

“…Patients included needed at least 1 of the following criteria used to qualify them at high risk of disease recurrence: history of previous sinus surgery; sinus surgery at ≤38 years of age; absolute eosinophilia ≥500 cells/mm; total serum immunoglobulin E levels ≥150 kIU/L; sinus culture of a Gram-negative organism at any time-point; and intraoperative finding of eosinophilic mucin. 11 Tissue samples were obtained by a mucosal brushing at the surface of the middle meatus at the time of surgery and at the 4-month time point. Total RNA was extracted from brushings using the RNeasy Mini Kit (Qiagen) according to the manufacturer's instructions and stored at −80°C until microarray measurements.…”

“…Identifying the molecular mechanisms implicated in successful recovery from ESS could lead to improved post-ESS outcomes by delineating dysfunctional processes that may potentially be manipulated by novel therapeutic interventions. As part of larger clinical trial described elsewhere, 11,12 this study explores the mechanistic underpinnings following a successful recovery from surgery for CRS by using transcriptomics to identify implicated pathways.…”

Year in review: 2021 IFAR article summary

“…Renteria et al 6 demonstrated that Staphylococcus aureus abundance in the sinonasal microbiome of patients with chronic rhinosinusitis (CRS) was decreased after 4 months of thrice weekly, low-dose azithromycin versus placebo in a double blind, randomized trial. Maniakas et al 7 conducted a double-blind, randomized trial demonstrating that low-dose oral azithromycin aids polyp resolution in patients with persistent polyposis despite ESS and high-volume corticosteroid irrigations. Siu et al 8 performed a randomized study of 30 patients undergoing ESS and analyzed sinonasal and stool samples using RNA sequencing.…”

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

“…Several studies have shown that the presence of bacterial biofilms has a negative impact on the healing process after ESS leading to persistence of postoperative symptoms and mucosal inflammation ( Bendouah et al., 2006 ; Psaltis et al., 2008 ; Singhal et al., 2011 ). A recent study looking at the contribution of microbes in early disease recurrence after ESS found that perioperative positive culture with S. aureus was associated with poor outcomes, and that clearance of the bacteria led to 75% remission at 4-months after surgery ( Maniakas et al., 2020 ). Focusing therapy on clearing perioperative infections in the initial postoperative period may alter the deleterious impact that bacterial pathogens have on the regeneration of epithelium and repopulation of the microbiome.…”