Thirty trials were included in the review, comprising 8215 participants. Fifteen trials used short-acting oral antibiotics, 4 used intramuscular ceftriaxone sodium, and 11 used oral azithromycin.
Short-acting antibiotics given for 48 hours or less: The summary OR for failures at one month or less in two trials that compared 48 hours or less of antibiotic treatment with at least 7 days gave was 2.99 (95% CI: 1.04, 8.54).
Short-acting antibiotics given for more than 48 hours: Twelve trials that reported outcomes at one month or less showed that the summary OR for treatment failure in children treated for 5 days, in comparison to children treated for 8 to 10 days, was 1.38 (95% CI: 1.15, 1.66). Treatment failure at an earlier evaluation point (8 to 19 days) in the 5-day treatment arm was more likely (1.52, 95% CI: 1.17, 1.98). The weighted mean failure rate was 19% (SE 7.6%) with 5 days of treatment and 13.7% (SE 6.4%) in the long treatment arm. The weighted summary risk difference was 7.8% (95% CI: 4%, 11.6%).
Among children treated with an antibiotic for 5 days and children treated for 8 to 10 days, primary outcomes at 20 to 30 days were not significantly different between the two groups (OR: 1.22; 95% CI: 0.98, 1.54). The weighted mean failure rate at 20 to 30 days was 15.7% (SE, 13.3%) with 5 days of treatment and 12.5% (SE, 12.4%) in the long treatment arm. The weighted summary risk difference was 2.3% (95% CI: -0.2%, 4.9%). This risk difference suggests that 44 children would need to be treated with the long course of short-acting antibiotics to avoid 1 treatment failure. The summary OR for antibiotic failure at 30 days or less in children younger than 2 years and those who were at least 2 years old was 0.71 (95% CI: 0.3, 1.64) and 1.01 (95% CI: 0.53, 1.94), respectively.
Outcome of ceftriaxone in the short-treatment arm: The outcomes of treatment with ceftriaxone for 1 month or less and for 3 months or less were not significantly different from those of treatment with a longer course of oral antibiotics, with summary ORs of 1.25 (95% CI: 0.90, 1.72) and of 0.91 (95% CI: 0.57, 1.47) respectively.
Outcome of azithromycin in the short-treatment arm: The summary OR for primary outcomes following 3 or 5 days of treatment with azithromycin in comparison with another antibiotic was 1.09 (95% CI: 0.86, 1.38). The summary ORs did not change when children were treated for 3 days only, when children were evaluated at 10 to 14 days, or when children were evaluated at 30 days. The odds of treatment failure with azithromycin was 1.92 (95% CI: 0.73, 5.04) in children younger than 2 years and 1.34 (95% CI: 0.61, 2.94) in older children.
Sensitivity analysis and publication bias: Treatment failures at 30 days or less were not significantly more likely in the short than long treatment arm among short-acting antibiotic trials grouped as:
1. High quality trials.
2. Trials with adequate treatment allocation.
3. Trials that excluded children with current or chronic OM.
The majority of summary ORs for primary outcomes at 20 to 30 days did not change during any of the sensitivity analyses.
A funnel plot showed no evidence of a publication bias in the meta-analysis trials.
Adverse effects: The summary OR for gastrointestinal side effects in the short-acting antibiotics trials was 0.54 (95% CI: 0.43, 0.66). An OR less than 1 was observed only in trials in which the short course of antibiotics trials was compared with a 10-day course of the standard formula of amoxicillin-clavulanate. Once these trials were excluded, there was no difference in the likelihood of gastrointestinal side effects following a short or long course of antibiotics (OR: 1.13; 95% CI: 0.81, 1.57). Children treated with axithromycin were also less likely to experience gastrointestinal side effects than children treated with a long course of antibiotics (OR: 0.26: 95% CI: 0.19, 0.37), which was most often amoxicillin-clavulanate.