Amoxicillin resulted in the lowest rates of both treatment failure and reinfection compared with other broad-spectrum antibiotics in children with uncomplicated acute otitis media (AOM), supporting its continued use as first-line treatment for AOM. These study findings were published in the Journal of Pediatrics.

In this year-long retrospective cohort study, researchers used prescription claims data to compare the effects of amoxicillin, amoxicillin-clavulanate, cefdinir, and azithromycin on the risk for treatment failure and reinfection in children with uncomplicated AOM. Treatment failure and reinfection were defined as the receipt of any new antibiotic prescription within 2 to 14 days and 15 to 30 days, respectively, after the initial AOM diagnosis. Logistic regression was used to estimate the risk for treatment failure and reinfection on the basis of antibiotic treatment type, with results adjusted for patient age, sex, geographic location, and clinical setting.

A total of 1,051,007 children aged between 6 months and 12 years were included in the final analysis, of whom 93% received long-term (≥10 days) and 7% received short-term (5-7 days) antibiotic treatment. The majority of children received amoxicillin (56.6%), followed by cefdinir (20.6%), amoxicillin-clavulanate (13.5%), and azithromycin (9.3%).

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The researchers assessed outcomes of treatment failure and reinfection using amoxicillin as a reference.

For reinfection, the risk was significantly increased (all P <.0001) and similar among children who received amoxicillin-calvulanate (adjusted odds ratio [aOR], 4.96; 95% CI, 4.80-5.13), cefdinir (aOR, 4.59; 95% CI, 4.45-4.74), and azithromycin (aOR, 4.36; 95% CI, 4.19-4.54).

For treatment failure, the risk was significantly increased for all other antibiotic agents (all P <.0001), with the highest risk observed among children who received azithromycin (aOR, 11.79; 95% CI, 11.19-12.43), followed by those who received amoxicillin-clavulanate (aOR, 11.36; 95% CI, 10.82-11.93) and those who received cefdinir (aOR, 9.66; 95% CI, 9.22-10.12).

Further analysis was performed to assess the combined risk for either treatment failure or reinfection by type of antibiotic treatment. Results showed that receipt of amoxicillin-clavulanate (aOR, 6.96; 95% CI, 6.77-7.15), cefdinir (aOR, 6.16; 95% CI, 6.00-6.32), and azithromycin (aOR, 6.58; 95% CI, 6.38-6.78) were all associated with an increased risk when compared with amoxicillin (all P <.0001).

Although treatment failure occurred more often among children who received short- vs long-term antibiotic treatment (2.3% vs 1.9%), reinfection occurred more often in those who received long- vs short-term antibiotic treatment (3.2% vs 2.1%). Overall, the associated risk for treatment failure (aOR, 1.43; 95% CI, 1.35-1.51; P <.0001) and reinfection (aOR, 0.78; 95% CI, 0.73-0.82; P <.0001) remained low for short- vs long-term antibiotic treatment.

Study limitations include the inability to confirm treatment adherence and AOM diagnosis accuracy, and the potential underestimation of prescription volumes and treatment failure and reinfection rates. The researchers also did not capture information on comorbidities that may have affected the type of antibiotic prescribed.

“[These] data support the [American Academy of Pediatrics’] AOM guidelines, which recommend amoxicillin as first-line therapy for most children who warrant an antibiotic and a short duration of antibiotics for older patients with non-severe AOM,” the researchers concluded.


Frost HM, Bizune D, Gerber JS, Hersh AL, Hicks LA, Tsay SV. Amoxicillin versus other antibiotic agents for the treatment of acute otitis media in children. J Pediatr. Published online August 6, 2022. doi:10.1016/j.jpeds.2022.07.053

This article originally appeared on Infectious Disease Advisor