In a nationwide retrospective study of commercially insured adults aged 18 to 64 years with outpatient, uncomplicated acute sinusitis, treatment failure rates were similar with standard-dose amoxicillin-clavulanate and standard-dose amoxicillin, although secondary infections occurred somewhat more often with amoxicillin-clavulanate.
Researchers analyzed more than 520,000 patients from a US health care utilization database (2018–2023). After propensity score matching, about 235,000 patients were included, with roughly equal numbers in each treatment group.
Treatment failure within 1 to 14 days occurred in about 3% of patients in both groups, with no meaningful difference between treatments. Treatment failure was defined as a new antibiotic dispensation, an outpatient or emergency department visit for sinusitis, or hospitalization for sinusitis or its complications.
Most treatment failures reflected a new antibiotic dispensation without a same-day visit, followed by outpatient visits with antibiotic switching. Emergency department encounters were rare, and inpatient encounters or complications requiring hospitalization were extremely rare.
Rates of antibiotic-associated adverse events were similar between groups (about 1% each), with gastrointestinal symptoms the most common.
However, secondary infections were more frequent with amoxicillin-clavulanate (about 1.2% vs 0.8%), although absolute differences were small. Yeast infections accounted for most events, and Clostridioides difficile infections were rare but occurred more often with amoxicillin-clavulanate.
In subgroup analyses, patients aged 18 to 44 years treated with amoxicillin-clavulanate had a slightly lower relative risk of treatment failure, but the absolute difference was small. No meaningful differences were observed across older age groups, sex, immune status, or dosing strategies.
Sensitivity analyses using alternative definitions, extended washout periods, and longer outcome windows showed consistent results, and negative control outcomes were similar between groups.
The researchers noted several limitations, including the observational design with potential residual confounding, lack of adherence data, absence of microbiologic confirmation, and restriction to commercially insured patients. Over-the-counter medication use, as well as race and socioeconomic data, were not captured.
“There was no difference in the risk of antibiotic-associated adverse events between treatment groups, although the risk of secondary infections was higher among patients dispensed amoxicillin-clavulanate,” said lead study researcher Timothy J. Savage, MD, of Brigham and Women’s Hospital, and colleagues. The findings support standard-dose amoxicillin as a preferred first-line treatment for adults with uncomplicated acute sinusitis, particularly in those without recent antibiotic exposure, when antibiotics are indicated.
Disclosures: Savage reported receiving grants to his institution from UCB and GSK outside the submitted work. Matthew P. Kronman, MD, reported receiving travel support from the Pediatric Infectious Diseases Society and personal fees from Scrudder Bass. Krista F. Huybrechts, PhD, reported receiving grants to her institution from Takeda, UCB, and GSK. The other researchers reported no conflicts of interest.
The study was funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development of the National Institutes of Health and the US Centers for Disease Control and Prevention.
The research is also being presented at the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) Global 2026 Congress.
Source: JAMA
