The Comparative Effectiveness and Safety of Amoxicillin Alone versus Amoxicillin/Clavulanate for the Outpatient Treatment of Acute Sinusitis in Children

Background: There are 4.9 million antibiotic prescriptions for acute sinusitis in children yearly in the US. While amoxicillin or amoxicillin/clavulanate are recommended as first line antibiotic treatment, no study has compared these medications to determine the best initial treatment for pediatric acute sinusitis since licensure of the first pneumococcal conjugate vaccine more than 20 years ago.

Objectives: To compare the effectiveness and safety of amoxicillin versus amoxicillin/clavulanate for the treatment of acute bacterial sinusitis in children.

Methods: Subjects < 18 years were identified via an outpatient encounter with an ICD-10 code for acute sinusitis (J01.x0) along with a same-day dispensation for amoxicillin or amoxicillin/clavulanate in the MarketScan Commercial Claims and Encounters Database between 2017 and 2020. Treatment failure -- a composite measure of a new antibiotic dispensation, an emergency department or inpatient encounter for acute sinusitis, or an inpatient encounter for a sinusitis complication -- was measured from 1 to 14 days (overall failure), 1 to 2 days (early failure, likely due to lack of tolerability), and 3 to 14 days (late failure, likely due to lack of effectiveness). Adverse events included gastrointestinal, hypersensitivity, skin, and kidney reactions, and yeast and C. difficile infection. Relative risks (95% confidence intervals) were estimated after propensity score matching to account for potential confounders.

Results: There were 177,200 amoxicillin-treated and 104,095 amoxicillin/clavulanate-treated patients. After PS matching, there were 87,905 patients per group. Overall failure occurred in 1,582 patients (1.80%) dispensed amoxicillin (referent) and 1,545 patients (1.76%) dispensed amoxicillin/clavulanate (RR 1.03, 95% CI: 0.98,1.10). Early failure was more frequent for those dispensed amoxicillin/clavulanate (RR 2.23, 95% CI: 1.92,2.59), while late failure was more frequent for those dispensed amoxicillin (RR 0.75, 95% CI: 0.69,0.81). Adverse events were slightly more frequent with amoxicillin/clavulanate (RR 1.11, 95% CI: 1.05,1.19). In subgroup analyses, there was no difference in overall failure for 0-5 years (RR 1.03, 95% CI: 0.89,1.19) and 6-11 years (RR 1.10, 95% CI: 0.96,1.26). For patients 12-17 years, the risk of failure was lower with amoxicillin/clavulanate (RR 0.89, 95% CI: 0.81,0.99).

Conclusions: For patients 11 years or younger, amoxicillin may be preferred as first line due to equivalent treatment failure and higher adverse event risk with amoxicillin/clavulanate. For patients ages 12-17 years, clinicians should consider balancing the limited added effectiveness against the increased side effect profile of amoxicillin/clavulanate if choosing that agent over amoxicillin.