Amoxicillin versus amoxicillin–clavulanate for treatment of acute sinusitis in adults

Currently, no consensus regarding exists on whether amoxicillin–clavulanate or amoxicillin should be first-line empiric treatment for uncomplicated acute sinusitis in adults. To investigate this issue, US researchers undertook a study to compare the risk of treatment failure and adverse events between standard-dose amoxicillin–clavulanate versus standard-dose amoxicillin for acute sinusitis in adults.1The new-user, active comparator retrospective cohort study used a nationwide healthcare utilization database to compare amoxicillin–clavulanate versus amoxicillin for adults aged 18–64 years with acute sinusitis in the outpatient setting. The six-year study included patients with a new diagnosis of acute sinusitis. Propensity score matching was used to help mitigate confounding.1 Standard-dose amoxicillin–clavulanate (875 mg/125 mg twice daily) was compared with standard-dose amoxicillin (875 mg twice daily or 500 mg three times daily). The primary outcome was treatment failure, defined as the first occurrence of a new antibiotic dispensation (with or without an outpatient visit), emergency department or inpatient encounter for acute sinusitis, or inpatient encounter for a sinusitis complication assessed one to 14 days after treatment initiation. Antibiotic-associated adverse events and secondary infections were also assessed.1Key results:The full cohort included 521,244 eligible patients. After propensity score matching, 234,608 patients were included (117,304 patients per group; 65.5% female; median age, 43 years). Treatment failure occurred in 3.1% of patients overall, with 0.03% requiring an emergency department or inpatient encounter. No difference was observed in the risk of treatment failure between the amoxicillin–clavulanate and amoxicillin groups (3.0% vs 3.1%; risk ratio [RR], 0.96 [95%CI, 0.92–1.01]), which was consistent across sensitivity analyses. No difference was noted in antibiotic-associated adverse events (1.3% vs 1.2%; RR, 1.04 [95%CI, 0.97–1.12]). The risk of secondary infections was higher for amoxicillin–clavulanate vs amoxicillin, including yeast infections (1.1% vs 0.8%; RR, 1.40 [95%CI, 1.29–1.53]) and Clostridioides difficile infections (0.04% vs 0.02%; RR, 2.14 [95%CI, 1.29–3.54]).1In this observational study of outpatients 18–64 years of age with acute sinusitis, no difference was seen in treatment failure with standard-dose amoxicillin–clavulanate versus standard-dose amoxicillin. Amoxicillin-clavulanate was associated with a higher (although rare) risk of secondary infections (yeast and C. difficile). The authors conclude their findings support standard-dose amoxicillin as a preferred empiric treatment for adults with uncomplicated acute sinusitis, when antibiotics are indicated.1 Note that the new Canadian Antibiotic Treatment Guidance online resource suggests watchful waiting (conditional recommendation) for management of acute sinusitis in adults. Clinicians may consider offering supportive treatments such as analgesics and saline nasal spray to provide symptomatic relief. Antibiotics may be considered if symptoms do not improve over a 10-day period or are severe. Although evidence of benefit with antibiotics exists in patients with symptoms lasting more than 10 days, the overall advantage over watchful waiting is small.2 If antibiotics are used, Canadian Antibiotic Treatment Guidance recommends amoxicillin 1 g orally three times daily for five days as the first-choice empiric treatment (conditional recommendation). Second-choice empiric therapy is amoxicillin/clavulanate 500 mg/125 mg orally three times daily or 875 mg/125 mg orally twice daily for five days (conditional recommendation). In patients with a severe penicillin allergy, doxycycline 100 mg orally twice daily for five days is recommended (conditional recommendation).2Reference:Savage TJ, Butler AM, Kronman MP, et al. Amoxicillin-clavulanate vs amoxicillin for acute sinusitis in adults. JAMA 2026. Published online April 18, 2026. (accessed April 18, 2026).Canadian Antibiotic Treatment Guidance. Firstline. Acute sinusitis – adults. (accessed April 18, 2026).

Amoxicillin versus amoxicillin–clavulanate for treatment of acute sinusitis in adults

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