Amoxicillin/clavulanic acid is ineffective at preventing otitis media in children with presumed viral upper respiratory infection: a randomized, double-blind equivalence, placebo-controlled trial.

To assess the equivalence of amoxicillin/clavulanic acid and placebo in the prevention of acute otitis media in children at high risk of acute otitis media who develop upper respiratory tract infection. This was a multicentre, equivalence, randomized, double-blind trial of two parallel groups comparing 5 days of amoxicillin/clavulanic acid 75 mg kg-1 day-1 (i.e. 25 mg kg-1 every 8 h) and placebo. The main outcome measure was acute otitis media occurring within 8-12 days of initiating treatment. Two hundred and three infants, aged 3 months-3 years with upper respiratory tract infection over 36 h and a history of recurrent acute otitis media were included over 8.5 months. Two children were lost to follow-up. Patient characteristics were similar in both groups. In the intention to treat analysis the frequency of acute otitis media was 16.2% (16/99) in the placebo group and 9.6% (10/104) in the amoxicillin/clavulanic acid group (P = 0.288). The difference between acute otitis media rates was 6.6% (one-sided 95% confidence interval of 14.3%). The occurrence of side-effects was similar in the amoxicillin/clavulanic acid and placebo groups. The difference in effectiveness between antibiotic and placebo was not greater than 14.3%, and we calculated that 94 children would need to be exposed to antibiotics to avoid six cases of acute otitis media. In view of the risk of development of resistance due to frequent exposure to antibiotics, our study supports the need for reduction in the administration of antibiotics in upper respiratory tract infection even in children at high risk of acute otitis media.