Background: Aetiopathogenesis of chronic rhinosinusitis is poorly understood. Recent researches emphasize culture independent molecular sequencing to identify clusters of flora which may function as drivers of inflammation. Studies also indicate that macrolides are as effective as corticosteroids in controlling chronic rhinosinusitis. In this study, we aimed to isolate microbial cultures from the middle meatii of patients suffering from chronic rhinosinusitis and observe the isolates for similarities and antibiotic sensitivity. Disease progression and response to treatment was also observed by objective evaluation using sino-nasal outcomes test-22 (SNOT-22) and Lund-Kennedy endoscopy scoring system. Methods: The patients underwent regular evaluation and diagnostic nasal endoscopy with cultures taken from middle meatus. The patients were treated with antibiotics as per cultured isolates. Results: The mean average Lund-Kennedy score and SNOT 22 scores dropped following a course of antibiotics. The patients also experienced symptomatic relief. The most commonly isolated organism among the samples evaluated was Pseudomonas aeruginosa. The best response to antibiotics was noted with Aminoglycosides. Total resistance (100%) to macrolides and amoxicillin was also noted which is contradictory to published literature. Conclusion: Understanding patients’ local microbiome may enable tailoring antibiotic regimens suited to patients . The present study also suggests revision of guidelines for antibiotic use and to develop personalised antibiogram for treating chronic rhinosinusitis.