Comparative Outcomes of Amoxicillin and Amoxicillin-Clavulanate in the Treatment of Acute Rhinosinusitis in Adults with Comorbidities: A Retrospective Study

Background/Objectives: The optimal antibiotic strategy for acute rhinosinusitis (ARS) in patients with comorbidities remains unclear. Guidelines often recommend amoxicillin-clavulanate (amx/clv) for high-risk patients, despite limited comparative evidence. This study compared ARS outcomes of patients with comorbidities receiving amoxicillin and amx/clv. Methods: This retrospective cohort study utilized electronic medical records from the Israeli community (2012–2023). Adults aged ≥18 years with ≥1 selected comorbidity and an ARS diagnosis were categorized according to the type of antibiotic prescribed. The primary outcome was treatment failure, defined as a follow-up ARS visit with an antibiotic prescription within 30 days of the initial visit. Secondary outcomes included ARS complications, emergency room referrals, chronic or subacute sinusitis diagnosis, and 90-day mortality rates. Adjusted odds ratios were estimated using multivariable logistic regression. Results: Of the 38,810 eligible patients, 4953 were prescribed amoxicillin, 7436 were prescribed amx/clv, and 26,421 were not prescribed antibiotics. Treatment failure rates were not significantly different when comparing amoxicillin to amx/clv or either antibiotic to no antibiotic therapy. Chronic or subacute sinusitis was more frequent with amx/clv than with amoxicillin alone. No significant intergroup differences were observed in terms of complications, emergency room referrals, or mortality rates. These findings remained consistent in a sensitivity analysis of filled prescriptions and when analyzing the outcomes of individual comorbidities separately. Conclusions: Among adults with specified comorbidities diagnosed with ARS, the rates of treatment failure, complications, and ER referrals did not differ significantly between amoxicillin and amx/clv, supporting narrow-spectrum therapy.