Amoxycillin as effective as amoxicillin-clavulanate in uncomplicated acute sinusitis: JAMA

This study is a novel new-user active comparator retrospective cohort study conducted using a large national health care utilization database. Researchers selected adults between the ages of 18 and 64 who were diagnosed with acute sinusitis for the first time in an outpatient care setting from January 1, 2018, to December 1, 2023.

Out of 521,244 participants that were initially eligible, investigators utilized propensity score matching to ensure proper comparisons and had 234,608 patients left equally distributed among two groups of 117,304 participants each. Patients included in the sample had 65.5% women and the median age of 43 years old. The investigation was conducted at the end of 2025 and was comparing standard-dose amoxicillin-clavulanate (875 mg-125 mg BID) and standard-dose amoxicillin (875 mg BID or 500 mg TID).

Key findings:

• Treatment failures were surprisingly low in both groups, being noted only in 3.1% of the participants. In total, less than 0.03% of patients experienced complications severe enough to warrant an emergency department visit or hospitalization.
• The two drugs exhibited similar risks of treatment failure, with 3.0% in the group receiving amoxicillin-clavulanate and 3.1% in the amoxicillin group.
• Risk ratio (0.96; 95% confidence interval [CI], 0.92-1.01) indicated that the "stronger" drug combination was no more effective at clearing the infection than the single-drug regimen, thus proving the hypothesis.
• Rates of adverse effects attributed to antibiotics were low in both study arms, namely 1.3% in the amoxicillin-clavulanate group and 1.2% in the amoxicillin group.
• Yet, the former drug was related to significantly elevated risks of certain adverse effects.
• Yeast infection was noted in 1.1% of patients from the amoxicillin-clavulanate arm and 0.8% from the other one, resulting in a 40% increased risk (risk ratio, 1.40).
• The most concerning side effect is Clostridioides difficile infection. Its incidence rate was 0.04% in the former arm and 0.02% in the latter, indicating a 2.14 risk ratio.

Amoxicillin in standard dose can be considered the better option to use as the initial therapy in uncomplicated adult cases of acute sinusitis since the effectiveness provided by the use of amoxicillin in standard dose matches those obtained when other antibiotic combinations are used. In conclusion, even though amoxicillin with clavulanate provides good results, it is accompanied by a greater occurrence of side effects and infections than the other antibiotic combinations. Through the use of amoxicillin, one can minimize the risk of developing infections such as C. difficile infection and yeast infection.

Reference:

Savage TJ, Butler AM, Kronman MP, et al. Amoxicillin-Clavulanate vs Amoxicillin for Acute Sinusitis in Adults. JAMA. Published online April 18, 2026. doi:10.1001/jama.2025.26902