Acute sinusitis leads to more antibiotic prescriptions for U.S. adults than any other condition, but there is no consensus on which antibiotic is preferred for uncomplicated cases. In a retrospective, nationwide study of more than 500,000 patients with acute sinusitis, a research team led by Mass General Brigham investigators found no major differences in measured outcomes between adults who received standard amoxicillin and amoxicillin‑clavulanate (a more powerful, combination antibiotic). Patients treated with amoxicillin‑clavulanate were at slightly higher risk of contracting secondary infections. Results are published in JAMA .
"Preventing unnecessary exposure to a broader‑spectrum antibiotic can help reduce the potential risk of spreading antibiotic resistance," said corresponding author Timothy Savage, MD, MPH, MSc, an associate epidemiologist in the Division of Pharmacoepidemiology and Pharmacoeconomics in the Mass General Brigham Department of Medicine. "Amoxicillin and amoxicillin‑clavulanate account for roughly 45% of antibiotic prescriptions for acute sinusitis, so it is essential that we identify the optimal option for patients. We found no observed benefit to using amoxicillin-clavulanate, which supports standard‑dose amoxicillin as the preferred choice for adults with uncomplicated acute sinusitis."
Clavulanate inhibits an enzyme that makes bacteria resistant to amoxicillin. However, not all bacteria that mediate acute sinusitis produce this enzyme — making it unclear if amoxicillin‑clavulanate offers any clinical advantage for patients with uncomplicated acute sinusitis.
The research team analyzed insurance claims data for patients diagnosed with acute sinusitis between January 2018 and December 2023. The cohort included 521,244 adults aged 18-64 years, who received a standard daily dose of either amoxicillin-clavulanate or amoxicillin. After matching patients by factors such as age, comorbidities and healthcare access, the researchers compared the risk of treatment failure (i.e., switching to a different antibiotic or returning to the doctor's office or emergency department) and adverse events between the antibiotics.
Treatment failure was rare and similar between both groups (~3%). Although guidelines suggest that amoxicillin‑clavulanate may benefit immunocompromised patients, investigators found no difference in treatment failure within this subgroup. There was no observed difference in antibiotic-associated adverse events, but the risk of secondary yeast or bacterial infections was slightly elevated in patients treated with amoxicillin‑clavulanate when compared to those who received amoxicillin.
"With nearly 5 million antibiotic prescriptions to adults with acute sinusitis in the U.S. each year, these findings have the potential to make a substantial impact on current treatment practices," said Savage. "Future research is needed to refine which patients will benefit from an antibiotic, and who are more likely to have viral infections and can be observed with supportive care."
Authorship: In addition to Savage, co-authors include Anne M. Butler, Matthew P. Kronman, Michael J. Durkin, Sushama Kattinakere Sreedhara, Sarah Kabbani, Lauri A. Hicks, and Krista F. Huybrechts.
Disclosures: Savage reported receiving grants to his institution from UCB and GSK outside the submitted work. Kronman reported receiving travel support from Pediatric Infectious Diseases Society and personal fees from Scrudder Bass outside the submitted work. Huybrechts reported receiving grants to her institution from Takeda, UCB, and GSK outside the submitted work.
Funding: This study was supported by the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) of the National Institutes of Health (NIH) (T32HD040128, K08HD110600) and the US Centers for Disease Control and Prevention (CDC) (U54CK000609).
Paper cited: Savage T et al. "Amoxicillin-Clavulanate vs Amoxicillin for Acute Sinusitis in Adults" JAMA DOI: 10.1001/jama.2025.26902s
