Amoxicillin/Clavulanate is More Effective than Azithromycin in Eradicating Pediatric Ear Infections

abstract & commentary

Synopsis: Amoxicillin/clavulanate treatment for AOM results in better clinical and bacteriologic cure than azithromycin therapy.

Source: Dagan R, et al. Bacteriologic and clinical efficacy of amoxicillin/clavulanate vs. azithromycin in acute otitis media. Pediatr Infect Dis J 2000;19:95-104.

This study from israeli, dominican, and u.s. medical centers examined children between 6 and 48 months of age with signs and symptoms of acute otitis media (AOM) of less than 24 hours in duration. The children were randomized in a single-blind fashion to receive either amoxicillin/clavulanate (45 mg/kg/day [amoxicillin component] in two divided doses for 10 days) or azithromycin (10 mg/kg on day 1, then 5 mg/kg once daily for 4 days). All children had tympanocentesis performed prior to the first antibiotic dose, and if positive, once again on days 4-6. Dagan and colleagues measured clinical response at 12-14 days, as well as bacteriologic cure rates.

This study included 238 children with AOM. Bacterial pathogens were identified by tympanocentesis in 71% at the start of the study. Haemophilus influenzae was the most common pathogen, followed by Streptococcus pneumoniae. Bacteriologic cure was noted in 83% of the children receiving amoxicillin/clavulanate, but only in 49% of those receiving azithromycin (P = 0.001). Clinical cure or improvement was noted in 86% of children in the amoxicillin/clavulanate group, compared to 70% of those in the azithromycin group (P = 0.023). There was no difference in overall adverse events between the groups, although amoxicillin/clavulanate had a higher rate of adverse experiences judged to be antibiotic-related (10% vs 2%, P = 0.006). Dagan et al conclude that amoxicillin/clavulanate treatment for AOM results in better clinical and bacteriologic cure than azithromycin therapy.

Comment by David J. Karras, MD, FAAEM, FACEP

While many antimicrobial agents are approved for treatment of pediatric AOM, the emergence of multiple-drug-resistant bacterial strains warrants re-examination of drug efficacy. In the case of acute pneumococcal ear infections, at least one-third of isolates are penicillin-resistant, 25% are trimethoprim-sulfamethoxazole-resistant, and at least 15% are resistant to macrolides. Drug resistance has also emerged in H. influenzae isolates. Because much of this resistance has been reported only in the past few years, we may not be able to rely on older studies of antibiotic effectiveness for AOM.

This is a powerful and important study. Bacteriologic cure rate is a much more stringent standard of antibiotic effectiveness than clinical cure rates alone. It should be remembered that the CDC recommends standard-dose amoxicillin for initial therapy of AOM in children at low risk for penicillin-resistant pneumococcal infections (e.g., those without multiple infections and not attending day care).1 Amoxicillin/clavulanate is generally reserved for children at higher risk for drug-resistant infections and for treatment failures. While azithromycin is certainly more convenient to administer, it does not appear to offer other therapeutic advantages over amoxicillin or amoxicillin/clavulanate. (Dr. Karras is Associate Professor of Medicine, Temple University School of Medicine, Director of Emergency Medicine Research, Temple University Hospital, Philadelphia, PA.)


1. Dowel SF, et al. Acute otitis media: Management and surveillance in an era of pneumococcal resistance—A report from the drug-resistant S. pneumoniae therapeutic working group. Pediatr Infect Dis J 1999;18:1-9.

All of the following are true regarding amoxicillin/clavulanate for treatment of acute otitis media in children except:

a. It has a higher clinical cure rate than azithromycin.

b. It has a higher bacteriologic cure rate than azithromycin.

c. It is less convenient to administer than azithromycin.

d. It is first-line therapy for uncomplicated infections.