Amoxicillin Alone Holds Up for Acute Sinusitis

For adults with uncomplicated acute sinusitis, standard-dose amoxicillin appeared to have a slight edge over amoxicillin-clavulanate, a propensity-matched observational study showed.

The two antibiotic regimens appeared equally effective with no difference in risk of treatment failure leading to a new antibiotic prescription or emergency or inpatient care, with a rate of 3.0% with the combination and 3.1% with amoxicillin alone (RR 0.96, 95% CI 0.92-1.01), according to Timothy J. Savage, MD, MPH, of Brigham and Women’s Hospital in Boston, and colleagues.

However, amoxicillin-clavulanate was associated with a “higher, albeit rare,” risk of adverse events, the researchers cautioned, which included secondary infections with yeast (1.1% vs 0.8%, RR 1.40, 95% CI 1.29-1.53) and Clostridioides difficile (0.04% vs 0.02%, RR 2.14, 95% CI 1.29-3.54), they reported in JAMA.

Study results were also presented at the European Society of Clinical Microbiology and Infectious Diseases congress in Munich.

“These findings support standard-dose amoxicillin as a preferred empiric treatment for adults with uncomplicated acute sinusitis without recent antibiotic exposure when antibiotics are indicated,” the group concluded, reiterating their conclusions from a similarly-designed comparison in children.

Acute sinusitis is the top reason for antibiotic prescribing in adults up to 65 years of age, with amoxicillin and amoxicillin-clavulanate being the most frequently prescribed drugs to treat it. The American Academy of Otolaryngology–Head and Neck Surgery recommends either drug, while the Infectious Diseases Society of America makes a “weak” recommendation for amoxicillin-clavulanate as first-line treatment based on low quality evidence.

The study used the Merative MarketScan Commercial nationwide healthcare utilization database to compare outcomes for 521,244 patients ages 18 to 64 years with outpatient acute sinusitis from 2018 through 2023 who were new users of standard-dose amoxicillin-clavulanate (875 mg to 125 mg twice daily) or standard-dose amoxicillin (875 mg twice daily or 500 mg three times daily). Propensity score matching was used to help mitigate confounding.

The primary endpoint, treatment failure, encompassed first occurrence of new antibiotic dispensation other than the index treatment with or without an outpatient encounter for acute sinusitis, an emergency department or inpatient encounter for acute sinusitis, or an inpatient encounter for a complication of sinusitis. But, treatment failure characterized by an emergency department or inpatient encounter was rare.

The most frequent reason for treatment failure was getting a different antibiotic without an outpatient encounter (2.2% with amoxicillin-clavulanate and 2.0% with amoxicillin alone, RR 1.09, 95% CI 1.03-1.15), “suggesting a patient may have called into the office to report persistent symptoms or intolerant adverse effects that resulted in a new prescription,” Savage’s group noted.

The second-most frequent reason was a return outpatient encounter with a new antibiotic dispensation (0.8% vs 1.1%, respectively, RR 0.73, 95% CI 0.67-0.79), although with a number needed to treat with amoxicillin-clavulanate of 331 to prevent one patient treated with amoxicillin from returning to the clinic for a new antibiotic prescription. “In the context of the association between broader-spectrum antibiotics and an increased risk of antimicrobial resistance, these findings do not support a clear preference for amoxicillin-clavulanate as first-line treatment, recommended by the Infectious Diseases Society of America guidelines,” Savage and colleagues wrote.

In subgroup analyses, amoxicillin-clavulanate had lower risk of treatment failure in patients ages 18 to 44 years compared with amoxicillin (RR 0.90, 95% CI 0.84-0.96), but with an absolute risk difference of just 0.27% and a number needed to treat of 365. No differences were seen between sexes or by amoxicillin dosing.

And while the American Academy of Otolaryngology–Head and Neck Surgery guidelines note immunocompromised status as one of several conditions that may benefit from amoxicillin-clavulanate over amoxicillin, the study showed no difference in treatment failure among patients who were immunocompromised versus not overall (both RR 0.96) or without a recent history of taking antibiotics or hospitalization.

Nor were there differences in antibiotic-associated adverse events (1.3% vs 1.2%, RR 1.04, 95% CI 0.97-1.12), the most common of which were gastrointestinal symptoms.

Limitations of the study included potential for residual confounding, lack of microbiologic data, and that the study captured medication dispensation without evaluating medication adherence. “However, treatment failure arising from nonadherence (e.g., due to medication intolerance) is an important clinical factor captured in this study,” the researchers noted.