Written by Samuel G. Rouleau
For pediatric patients with acute sinusitis, amoxicillin-clavulanate does not offer treatment benefit over amoxicillin alone and is more likely to be associated with gastrointestinal (GI) side effects and yeast infections than amoxicillin.
Sorry Eminem, amoxicillin is real enough!
Approximately 4.9 million antibiotic regimens are prescribed in the US for pediatric acute sinusitis each year. Amoxicillin and amoxicillin-clavulanate account for 65% of all prescriptions for acute sinusitis. Currently, the IDSA recommends amoxicillin-clavulanate as first line, while the AAP recommends amoxicillin with OR without clavulanate as first line. This study is the first to compare amoxicillin and amoxicillin-clavulanate since the introduction of the pneumococcal conjugate vaccine two decades ago.
This was a nationwide cohort study of 320,141 commercially insured patients, ages 17 and below, diagnosed with acute sinusitis from 2017-2021. The primary outcome was treatment failure within 14 days, which was defined as a second antibiotic prescribed after the initial antibiotic or an emergency department or inpatient encounter for sinusitis or related complications. To address potential confounders, the investigators analyzed an extensive list of covariates and used propensity-score matching1 to create the two propensity-matched cohorts with 99,471 patients each.
Amoxicillin-clavulanate was more likely to be prescribed at urgent care locations and to adolescents (ages 12-17). There was no significant difference in treatment failure between amoxicillin-clavulanate and amoxicillin: 1.7% versus 1.8%, RR 0.98 (95%CI 0.92-1.05). GI symptoms and yeast infections were both more likely in those receiving amoxicillin-clavulanate. When stratified by age, patients aged 12-17 had lower treatment failure with amoxicillin-clavulanate (RR 0.87, 95%CI 0.79-0.95) with an estimated number needed to treat of 417, and adverse events in this age category were equivalent.
How will this change my practice?
Amoxicillin will be my first choice for pediatric acute sinusitis, unless there is specific reason for amoxicillin-clavulanate (e.g. local area with high rates of penicillin resistance). Even in patients aged 12-17, I will still reach for amoxicillin first, as the estimated number needed to treat of 417 is not compelling. This is now the third study that shows equivalence between amoxicillin and amoxicillin-clavulanate for sinusitis.2-4 Hopefully, this paper will spur societies to re-consider their guidelines.
Dr. Walsh-Blackmore wrote a Journal Feed post on a randomized clinical trial of children with acute sinusitis who were randomized to amoxicillin-clavulanate or placebo.5 It makes me wonder if amoxicillin would have done just as well.
Treatment Failure and Adverse Events After Amoxicillin-Clavulanate vs Amoxicillin for Pediatric Acute Sinusitis. JAMA. 2023 Sep 19;330(11):1064-1073. doi: 10.1001/jama.2023.15503.
- Austin PC. An Introduction to Propensity Score Methods for Reducing the Effects of Confounding in Observational Studies. Multivariate Behav Res. 2011;46(3):399-424. doi:10.1080/00273171.2011.568786
- Wald ER, Chiponis D, Ledesma-Medina J. Comparative effectiveness of amoxicillin and amoxicillin-clavulanate potassium in acute paranasal sinus infections in children: a double-blind, placebo-controlled trial. Pediatrics. 1986;77(6):795-800.
- Garbutt JM, Goldstein M, Gellman E, Shannon W, Littenberg B. A randomized, placebo-controlled trial of antimicrobial treatment for children with clinically diagnosed acute sinusitis. Pediatrics. 2001;107(4):619-625. doi:10.1542/peds.107.4.619
- Rovelsky SA, Remington RE, Nevers M, et al. Comparative effectiveness of amoxicillin versus amoxicillin-clavulanate among adults with acute sinusitis in emergency department and urgent care settings. J Am Coll Emerg Physicians Open. 2021;2(3):e12465. Published 2021 Jun 16. doi:10.1002/emp2.12465
- Shaikh N, Hoberman A, Shope TR, et al. Identifying Children Likely to Benefit From Antibiotics for Acute Sinusitis: A Randomized Clinical Trial. JAMA. 2023;330(4):349-358. doi:10.1001/jama.2023.10854