The treatment of acute sinusitis in adults in the outpatient setting has always proved challenging from an antimicrobial stewardship perspective. Clinical practice guidelines from both IDSA, published in 2012, and the American Academy of Otolaryngology-Head and Neck Surgery, published in 2025, recommend antibiotics only for persistent or severe symptoms, leading to a rather subjective decision to prescribe that is often influenced by logistical factors and other externalities.
When antimicrobial therapy is indicated, IDSA guidelines recommend amoxicillin-clavulanate, while AAO-HNS guidelines recommend amoxicillin or amoxicillin-clavulanate, with the latter reserved for (not particularly well-validated) situations in which bacterial resistance is likely. Clavulanate does not come without cost, however, as amoxicillin-clavulanate has been demonstrated to have a higher risk of promoting Clostridium difficile-associated disease and other side effects as compared to amoxicillin alone.
A recent article in JAMA used the Merative MarketScan commercial database to retrospectively identify 117,308 patients with an ICD-10 code for acute sinusitis who received amoxicillin-clavulanate that were propensity score-matched 1:1 on over 70 covariates to patients who received amoxicillin alone. Patients with chronic sinusitis and concurrent infection were excluded.
Treatment failure (defined as receipt of a new antibiotic or emergency department or inpatient encounter for acute sinusitis or complication thereof) was nearly identical (3.0% with amoxicillin-clavulanate vs. 3.1% with amoxicillin). Emergency department encounters (0.035% vs. 0.022%) and inpatient complications (0.003% vs. 0.001%) were exceptionally rare. Antibiotic-associated adverse events were similar (1.3% vs. 1.2%), though secondary infections were more frequent in the amoxicillin-clavulanate cohort (1.2% vs. 0.8%), most frequently yeast infections (1.1% vs. 0.8%). C. difficile infections were more frequent in those treated with amoxicillin-clavulanate (0.04% vs. 0.02%).
At minimum, this article suggests that the AAO-HNS-endorsed approach of not always defaulting to amoxicillin-clavulanate as first-line antimicrobial therapy for acute sinusitis is likely in order, pending more prospective data.
