Clinical Question: Is azithromycin or amoxicillin-clavulanate preferred for the treatment of children with persistent or recurrent otitis media?
Setting: Outpatient (any)
Study Design: Randomized controlled trial (double-blinded)
Synopsis: Investigators identified children between six months and six years of age who had recurrent or persistent acute otitis media. Recurrent acute otitis media was defined as one or more episodes in the past month, three or more episodes in the past six months, or four or more episodes in the past 12 months. Persistent acute otitis media was defined as the persistence of signs or symptoms for 48 hours after the initiation of treatment. Acute otitis media was diagnosed if children had at least two signs of middle ear effusion and two signs or symptoms of inflammation. Children weighing more than 25 kg (55 lb), requiring hospitalization, who had significant comorbidities, who had tubes, or who had evidence of chronic or complicated infection were excluded. Patients and their physicians (who were the outcome assessors) were appropriately blinded, although we are not told how children were assigned to the treatment groups.
Of 304 children who were randomized, 300 received at least one dose of a study drug, and 296 were included in the intention-to-treat analysis (three did not actually have acute otitis media, and one did not meet inclusion criteria). Most of the children (66 percent) had recurrent acute otitis media; the remainder had persistent acute otitis media or both persistent and recurrent acute otitis media.
Children were randomized to receive high-dose amoxicillin-clavulanate (90 mg-6.4 mg per kg per day in two divided doses) for 10 days or high-dose azithromycin (20 mg per kg given once daily) for three days. There was no difference in clinical success rates at days 12 to 16 (86 percent for azithromycin versus 84 percent for amoxicillin-clavulanate). A small advantage was noted with azithromycin therapy at 28 to 32 days (72 versus 61 percent in the amoxicillin-clavulanate group; P = .047, number needed to treat = nine). Diarrhea was somewhat more common in the amoxicillin-clavulanate group (29.9 versus 19.6 percent in the azithromycin group; P = .045, number needed to harm = 10). This study was sponsored by the manufacturer of azithromycin.
Bottom Line: For every 10 children with persistent or recurrent otitis media who receive high-dose azithromycin for three days instead of high-dose amoxicillin-clavulanate for 10 days, there is one additional clinical cure at one month and one fewer episode of diarrhea. However, clinical success at two weeks does not differ. (Level of Evidence: 1b)