Abstract & Commentary

Antimicrobial Treatment of Acute Otitis Media — It Works!

By Hal B. Jenson, MD, FAAP, Professor of Pediatrics, Tufts University School of Medicine; Chief Academic Officer, Baystate Medical Center, Springfield, MA, is Associate Editor for Infectious Disease Alert.

Dr. Jenson reports no financial relationships relevant to this field of study.

Synopsis: In a placebo-controlled trial with strict criteria for diagnosis of acute otitis media in young children, amoxicillin-clavulanate reduced treatment failure from 44.9% to 18.6% (P<0.001), with an overall reduction in treatment failure of 62%. Amoxicillin-clavulanate was associated with mild diarrhea that did not require discontinuation of study drug in almost half of recipients.

Source: Tähtinen PA, et al. A placebo-controlled trial of antimicrobial treatment for acute otitis media. N Engl J Med 2011;364:116-126.

A randomized, double-blind, placebo-controlled trial of the efficacy of oral amoxicillin-clavulanate treatment (40 mg amoxicillin + 5.7 mg clavulanate/kg/day divided into 2 daily doses for 7 days) of acute otitis media was conducted among children 6-35 months of age in Finland. Three diagnostic criteria were required for study eligibility: 1) middle-ear fluid demonstrated by pneumatic otoscopy with at least two tympanic membrane findings of bulging position, decreased or absent mobility, abnormal color or opacity not due to scarring, and air-fluid interfaces; 2) distinct erythematous patches or streaks or increased vascularity over full, bulging, or yellow tympanic membrane; and 3) acute symptoms of fever, ear pain, or respiratory tract symptoms. Assessments were performed by experienced otoscopists.

Adherence to the study drug, as assessed by different measures, was 94%-99%, with no significant differences between the two groups. Treatment failure, measured by six independent components, occurred in 30 of the 161 children (18.6%) in the amoxicillin-clavulanate group and 71 of the 158 children (44.9%) in the placebo group (p < 0.001). Kaplan-Meier analysis demonstrated a separation between the curves beginning at the first scheduled return visit on study day 3. To avoid treatment failure in one child, 3.8 children (95% CI, 2.7-6.2) would have to be treated with amoxicillin-clavulanate.

Rescue treatment was initiated in 11 of 30 children in the amoxicillin-clavulanate group (36.7%) and in 53 of 71 children in the placebo group (74.6%) who had treatment failure (p = 0.007). The need for rescue treatment was reduced by 81% with amoxicillin-clavulanate as compared to placebo. There was not a significant difference in the use of analgesic or antipyretic agents, with a mean duration of use of 3.6 days in the amoxicillin-clavulanate group and 3.4 days in the placebo group. Amoxicillin-clavulanate resulted in significantly improved otoscopic findings at the end of treatment (p < 0.001) and time to resolution of fever, poor appetite, decreased activity, and irritability (p < 0.001). Parents of children attending daycare missed significantly fewer days in the amoxicillin-clavulanate group (81 days) than in the placebo group (101 days) (p = 0.005).

Diarrhea developed in 77 children (47.8%) in the amoxicillin-clavulanate group and 42 children (26.6%) in the placebo group. The diarrhea was non-watery and non-bloody, and did not require discontinuation of the study drug.


There are innumerable published studies, which span the spectrum of scientific rigor, over the past decades reporting findings of antibiotic treatment of otitis media. This very rigorous study is of interest because of two findings that differ from what is generally believed — a higher rate (44.9%) of treatment failure with placebo and a greater and earlier benefit of antibiotic treatment. Several meta-analyses of antibiotic treatment of otitis media report that the number of children needed to treat to benefit one child is from 7 to 17, compared to the 3.8 in this study. Rescue treatment of children in the amoxicillin-clavulanate group (6.8% overall) was required about as often as in the treatment group of other studies, but required in 33.5% of children in the placebo group, compared to an average of 12% in other studies. These key differences are likely attributable to the scientific rigor of this study in diagnostic criteria and defining treatment failure, and the use of the most appropriate drug and dosage for otitis media.

There is some controversy over the appropriate management of otitis media in young children. In 2004, the American Academy of Pediatrics recommended observation without the use of antibiotics for selected children with acute otitis media. Even in this study, half of children in the placebo group did not have treatment failure, and two-thirds did not need rescue treatment.

The 2004 recommendation was qualified by acknowledging that it "was based on randomized, controlled trials with limitations." This new study is important, and provides a contemporary, rigorous answer to the question of the benefit of initial antibiotic treatment vs. observation for acute otitis media. These results demonstrate a clear benefit of appropriate antibiotic treatment to a degree that is greater than understood previously, including the finding of significant improvement by study day 3. Though some cases of acute otitis media in children will indeed resolve spontaneously, we do not have the diagnostic acumen to identify that subset of cases. Thus, these results indicate that all children with acute otitis media 6 to 35 months of age should be treated with amoxicillin-clavulanate as the initial management.