Amoxicillin-Clavulanate vs Amoxicillin for Sinusitis

Amoxicillin-clavulanate was not linked to lower treatment failure but was associated with a slightly higher risk of secondary infections compared with amoxicillin in adults with uncomplicated acute sinusitis.

By
Kathryn Wighton
April 20, 2026
3 min

Conexiant

Overview

A large retrospective study found similar treatment failure rates between standard-dose amoxicillin-clavulanate and amoxicillin in adults with uncomplicated acute sinusitis. However, secondary infections were slightly more frequent with amoxicillin-clavulanate.

Background

Acute sinusitis is commonly treated with antibiotics, but the optimal choice remains debated. Amoxicillin and amoxicillin-clavulanate are frequently prescribed, with the latter often reserved for suspected resistant infections. Understanding comparative effectiveness and safety is important to guide first-line therapy. This study analyzed over 520,000 commercially insured adults to compare outcomes between these two regimens.

Data Highlights

Outcome	Amoxicillin-Clavulanate	Amoxicillin
Treatment failure (1-14 days)	~3%	~3%
Antibiotic-associated adverse events	~1%	~1%
Secondary infections	1.2%	0.8%
Clostridioides difficile infections	Rare, more frequent	Rare

Key Findings

Treatment failure rates were approximately 3% and similar between both antibiotic groups.
Most treatment failures involved new antibiotic prescriptions without same-day visits.
Antibiotic-associated adverse events occurred in about 1% of patients in each group, predominantly gastrointestinal symptoms.
Secondary infections, mainly yeast infections, were more frequent with amoxicillin-clavulanate (1.2% vs 0.8%).
Clostridioides difficile infections were rare but slightly more common with amoxicillin-clavulanate.
Subgroup analyses showed a slight relative risk reduction in treatment failure with amoxicillin-clavulanate in patients aged 18-44, but absolute differences were small.

Clinical Implications

Standard-dose amoxicillin is supported as the preferred first-line treatment for uncomplicated acute sinusitis in adults, especially those without recent antibiotic exposure. Amoxicillin-clavulanate does not reduce treatment failure rates but is associated with a higher risk of secondary infections. Clinicians should weigh these factors when selecting antibiotic therapy.

Conclusion

This large observational study indicates no meaningful difference in treatment failure between amoxicillin and amoxicillin-clavulanate for uncomplicated acute sinusitis, with a slightly increased risk of secondary infections linked to amoxicillin-clavulanate. These findings favor amoxicillin as the initial antibiotic choice.