The pathogenesis of chronic rhinosinusitis (CRS) is complex and multifactorial. The role of microorganisms in CRS has not yet been fully defined. However, biofilms, microbiome dysbiosis, bacterial superantigens, antimicrobial resistance, and fungal antigens have all been suggested as contributors. The complexity of its pathogenesis can make treatment of recalcitrant CRS especially challenging. Topical antibiotic therapy provides direct delivery of the therapeutic agent in high concentrations to the sinonasal mucosa. Systemic absorption from topical therapy is low, allowing side effects of systemic antimicrobial therapy to be minimized. There is the potential for mucociliary injury which may be associated with local adverse effects such as nasal congestion, epistaxis, irritation, and cough [1–3].