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Refractory chronic rhinosinusitis (CRS) remains a significant burden for patients, often 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).

A double‐blind, randomized, placebo‐controlled trial was completed in a single tertiary‐care center assessing the addition of 250 mg azithromycin, 3 times per week for 16 weeks, in adults failing ESS and high‐volume BNIs. Associated comorbidities, as well as symptomatologic, microbiologic, and serologic values, were …