Level 2: Mid-level evidence

When antibiotics are needed for treating acute otitis media (AOM) in children, amoxicillin is the first-line agent recommended by the American Academy of Pediatrics. Macrolides, such as azithromycin or clarithromycin, are recommended as alternatives for patients with type 1 hypersensitivity reactions. A recent systematic review of low-quality trials comparing macrolide antibiotics (azithromycin and clarithromycin) with amoxicillin-containing antibiotics for AOM in children found that macrolide antibiotics were associated with a modest increase in risk of clinical failure (Ann Pharmacother. 2010;44:471-478). Ten randomized trials compared these macrolide antibiotics with amoxicillin or amoxicillin plus clavulanate in 2,766 children age six months to 15 years with AOM. The risk of clinical failure was increased with macrolide antibiotic use (relative risk [RR] 1.3, 95% confidence interval [CI] 1.07-1.6, NNH 32 [range from meta-analysis 21-56]). In subgroup analyses, azithromycin had a significantly higher rate of failure (RR 1.34, 95% CI 1.06-1.7) compared with amoxicillin-containing antibiotics, but clarithromycin trials showed no significant difference in failure rates (RR 1.17, 95% CI 0.65-2.12). Macrolide antibiotic use was also associated with significantly reduced adverse effects, including risk of diarrhea. A trend toward higher failure rates with macrolides was observed in children younger than age four years.