Antibiotics for acute middle ear infection (acute otitis media) in children

Review questions

This review compared 1) the clinical effectiveness and safety of antibiotics against placebo in children with an acute middle ear infection (acute otitis media (AOM)) and 2) the clinical effectiveness and safety of antibiotics against expectant observation (observational approaches in which prescriptions may or may not be provided) in children with AOM.

Background

AOM is one of the most common infections in early infancy and childhood, causing pain and general symptoms of illness such as fever, irritability and problems feeding and sleeping. By three years of age, most children have had at least one AOM episode. Though AOM usually resolves without treatment, it is often treated with antibiotics.

Study characteristics

The evidence in this review is current to 26 April 2015.

For the review of antibiotics against placebo we included 13 trials (3401 children aged between two months and 15 years) from high-income countries with generally low risk of bias. Three trials were performed in a general practice (GP) setting, six in an outpatient hospital setting and four in both settings.

For the review of antibiotics against expectant observation, five trials (1149 children) from high-income countries were eligible with low to moderate risk of bias. Two trials were performed in a GP setting and three in an outpatient hospital setting. Four trials (1007 children) reported outcome data that could be used for this review.

Key results

We found that antibiotics were not very useful for most children with AOM; antibiotics did not decrease the number of children with pain at 24 hours (when 60% of children were better anyway), only slightly reduced the number of children with pain in the days following and did not reduce the number of children with late AOM recurrences and hearing loss (that can last several weeks) at three months compared with placebo. However, antibiotics did slightly reduce the number of children with perforations of the eardrum and AOM episodes in the initially unaffected ear compared with placebo. Results from an individual patient data meta-analysis including data from six high-quality trials (1643 children), which were also included as individual trials in our review, showed that antibiotics seem to be most beneficial in children younger than two years of age with infection in both ears and in children with both AOM and a discharging ear.

We found no difference between immediate antibiotics and expectant observational approaches in the number of children with pain three to seven days and 11 to 14 days after assessment. Furthermore, no differences in the number of children with hearing loss at four weeks, perforations of the eardrum and late AOM recurrences were observed between groups.

There was not enough information to know if antibiotics reduced rare complications such as mastoiditis (infection of the bones around the ear). All of the studies included in this review were from high-income countries. Data are lacking from populations in which the AOM incidence and risk of progression to mastoiditis is higher.

Antibiotics caused unwanted effects such as diarrhoea, vomiting and rash and may also increase resistance to antibiotics in the community. It is difficult to balance the small benefits against the small harms of antibiotics in children with AOM. However, for most children with mild disease in high-income countries, an expectant observational approach seems justified.

Quality of the evidence

We judged the quality of the evidence to be high for most of the outcomes in the review of antibiotics against placebo (this means that further research is very unlikely to change our confidence in the estimate of effect).

For the review of immediate antibiotics versus expectant observation, we judged the evidence to be of moderate quality for most of the outcomes (this means that further research is likely to have an important impact on how confident we are in the results and may change those results). Quality was affected by concerns about sample size (perforation of the eardrum, rare complications) and the large number of children who are 'lost to follow-up' (pain at days 11 to 14, hearing loss at four weeks and late AOM recurrences).

Authors' conclusions: 

This review reveals that antibiotics have no early effect on pain, a slight effect on pain in the days following and only a modest effect on the number of children with tympanic perforations, contralateral otitis episodes and abnormal tympanometry findings at two to four weeks and at six to eight weeks compared with placebo in children with AOM. In high-income countries, most cases of AOM spontaneously remit without complications. The benefits of antibiotics must be weighed against the possible harms: for every 14 children treated with antibiotics one child experienced an adverse event (such as vomiting, diarrhoea or rash) that would not have occurred if antibiotics were withheld. Therefore clinical management should emphasise advice about adequate analgesia and the limited role for antibiotics. Antibiotics are most useful in children under two years of age with bilateral AOM, or with both AOM and otorrhoea. For most other children with mild disease in high-income countries, an expectant observational approach seems justified.

Read the full abstract...
Background: 

Acute otitis media (AOM) is one of the most common diseases in early infancy and childhood. Antibiotic use for AOM varies from 56% in the Netherlands to 95% in the USA, Canada and Australia. This is an update of a Cochrane review first published in The Cochrane Library in Issue 1, 1997 and previously updated in 1999, 2005, 2009 and 2013.

Objectives: 

To assess the effects of antibiotics for children with AOM.

Search strategy: 

We searched CENTRAL (2015, Issue 3), MEDLINE (1966 to April week 3, 2015), OLDMEDLINE (1958 to 1965), EMBASE (January 1990 to April 2015), Current Contents (1966 to April 2015), CINAHL (2008 to April 2015) and LILACS (2008 to April 2015).

Selection criteria: 

Randomised controlled trials (RCTs) comparing 1) antimicrobial drugs with placebo and 2) immediate antibiotic treatment with expectant observation (including delayed antibiotic prescribing) in children with AOM.

Data collection and analysis: 

Two review authors independently assessed trial quality and extracted data.

Main results: 

For the review of antibiotics against placebo, 13 RCTs (3401 children and 3938 AOM episodes) from high-income countries were eligible and had generally low risk of bias. The combined results of the trials revealed that by 24 hours from the start of treatment, 60% of the children had recovered whether or not they had placebo or antibiotics. Pain was not reduced by antibiotics at 24 hours (risk ratio (RR) 0.89, 95% confidence interval (CI) 0.78 to 1.01) but almost a third fewer had residual pain at two to three days (RR 0.70, 95% CI 0.57 to 0.86; number needed to treat for an additional beneficial outcome (NNTB) 20). A quarter fewer had pain at four to seven days (RR 0.76, 95% CI 0.63 to 0.91; NNTB 16) and two-thirds fewer had pain at 10 to 12 days (RR 0.33, 95% CI 0.17 to 0.66; NNTB 7) compared with placebo. Antibiotics did reduce the number of children with abnormal tympanometry findings at two to four weeks (RR 0.82, 95% CI 0.74 to 0.90; NNTB 11), at six to eight weeks (RR 0.88, 95% CI 0.78 to 1.00; NNTB 16) and the number of children with tympanic membrane perforations (RR 0.37, 95% CI 0.18 to 0.76; NNTB 33) and halved contralateral otitis episodes (RR 0.49, 95% CI 0.25 to 0.95; NNTB 11) compared with placebo. However, antibiotics neither reduced the number of children with abnormal tympanometry findings at three months (RR 0.97, 95% CI 0.76 to 1.24) nor the number of children with late AOM recurrences (RR 0.93, 95% CI 0.78 to 1.10) when compared with placebo. Severe complications were rare and did not differ between children treated with antibiotics and those treated with placebo. Adverse events (such as vomiting, diarrhoea or rash) occurred more often in children taking antibiotics (RR 1.38, 95% CI 1.19 to 1.59; number needed to treat for an additional harmful outcome (NNTH) 14). Funnel plots do not suggest publication bias. Individual patient data meta-analysis of a subset of included trials found antibiotics to be most beneficial in children aged less than two years with bilateral AOM, or with both AOM and otorrhoea.

For the review of immediate antibiotics against expectant observation, five trials (1149 children) from high-income countries were eligible and had low to moderate risk of bias. Four trials (1007 children) reported outcome data that could be used for this review. From these trials, data from 959 children could be extracted for the meta-analysis of pain at three to seven days. No difference in pain was detectable at three to seven days (RR 0.75, 95% CI 0.50 to 1.12). One trial (247 children) reported data on pain at 11 to 14 days. Immediate antibiotics were not associated with a reduction in the number of children with pain (RR 0.91, 95% CI 0.75 to 1.10) compared with expectant observation. Additionally, no differences in the number of children with abnormal tympanometry findings at four weeks, tympanic membrane perforations and AOM recurrence were observed between groups. No serious complications occurred in either the antibiotic or the expectant observation group. Immediate antibiotics were associated with a substantial increased risk of vomiting, diarrhoea or rash compared with expectant observation (RR 1.71, 95% CI 1.24 to 2.36; NNTH 9).

Results from an individual patient data meta-analysis including data from six high-quality trials (1643 children) that were also included as individual trials in our review showed that antibiotics seem to be most beneficial in children younger than two years of age with bilateral AOM (NNTB 4) and in children with both AOM and otorrhoea (NNTB 3).

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