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1Department of Otorhinolaryngology and Julius Centre for Health Sciences and Primary Care, University Medical Centre, Utrecht, The Netherlands
2Julius Centre for Health Sciences and Primary Care, University Medical Centre, Utrecht, The Netherlands
3evidENT at Ear Institute, University College London, London, UK
RPV and RAMJD are authors of references cited in this review. AGMS's institute has received a grant from GlaxoSmithKline for a study on the microbiology of acute tympanostomy tube otorrhoea.
RPV, RAMJD, and AGMS would like to acknowledge Maroeska M. Rovers, a previous contributor to this review.
#
Contributed equally.
Roles
Roderick P Venekamp: GP trainee and postdoctoral researcher
Roger AMJ Damoiseaux: Professor of General Practice/Head vocational training
Anne GM Schilder: Professor of Paediatric Otorhinolaryngology
Acute otitis media (AOM) is a common reason for primary care visits in children. Yet, there is considerable debate on the most effective treatment.
Methods and outcomes
We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of treatments (analgesics, antibiotics, and myringotomy) in children with AOM? We searched: Medline, Embase, The Cochrane Library, and other important databases up to October 2013 (Clinical Evidence reviews are updated periodically; please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).
Results
We found 17 studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.
Conclusions
In this systematic review we present information relating to the effectiveness and safety of the following interventions: analgesics, antibiotics, delayed antibiotics, immediate antibiotics, longer courses of antibiotics, and myringotomy.
Key Points
Acute otitis media (AOM) is characterised by the presence of middle-ear effusion together with an acute onset of signs and symptoms caused by middle-ear inflammation.
Middle-ear effusion without signs of an acute infection indicates otitis media with effusion (OME or 'glue ear'), while chronic suppurative otitis media (CSOM) is characterised by continuing (>3 months) middle-ear inflammation and ear discharge through tympanic membrane perforation or ventilation tubes (grommets). Interventions for these conditions are assessed in separate reviews in Clinical Evidence (see the reviews Otitis media with effusion in children and Chronic suppurative otitis media).
The most common pathogens in AOM are Streptococcus pneumoniae, non-typeable Haemophilus influenzae, and Moraxella catarrhalis. Local resistance patterns are important when choosing the type of antibiotic.
In the UK, antibiotics are prescribed for about 87% of AOM episodes in children's primary care visits.
Without antibiotics, the clinical symptoms of AOM resolve in about 80% of children within 3 days.
Analgesics (paracetamol, non-steroidal anti-inflammatory drugs [NSAIDs], and topical anaesthetic drops) may reduce earache compared with placebo.
Antibiotics seem to reduce pain at 2 to 7 days compared with placebo, but they increase the risks of vomiting, diarrhoea, or rash.
We do not know whether any one antibiotic regimen should be used in preference to another, although amoxicillin may be more effective than macrolides and cephalosporin.
Immediate antibiotic use seems most beneficial in children aged under 2 years with bilateral AOM and in children with AOM presenting with ear discharge.
Immediate antibiotic treatment may provide short-term reduction for some symptoms of AOM, but it increases the risk of rash and diarrhoea compared with delayed treatment.
Longer courses of antibiotics reduce short-term treatment failure but have no benefit in the longer term compared with shorter regimens (7 days or less).
Myringotomy may be less effective than antibiotics at reducing symptoms, and we found no evidence that it was superior to no myringotomy.
Clinical context
General background
Acute otitis media (AOM) is one of the most common infections in (early) childhood. It is defined as the presence of middle-ear effusion in conjunction with rapid onset of one or more signs or symptoms of inflammation of the middle ear such as fever, otalgia, and ear discharge (otorrhoea). Uncomplicated AOM is limited to the middle-ear cleft.
Focus of the review
This review includes evidence on the effectiveness and safety of the following interventions for a single episode of acute otitis media: analgesics, short-courses of (delayed and immediate) antibiotics (in specific subgroups of children), longer courses of antibiotics, and myringotomy.
Comments on evidence
Although analgesics are recognised as the cornerstone of treatment of AOM in children, we found only low-quality evidence on the effectiveness and safety of paracetamol, non-steroidal anti-inflammatory drugs, and topical anaesthetic ear drops. The quality of evidence regarding the effectiveness and safety of antibiotics was assessed as being of low to moderate using a GRADE evaluation. The quality of studies comparing different antibiotics with each other was judged to be very low.
Search and appraisal summary
The update literature search for this review was carried out from the date of the last search, September 2009, to October 2013. For more information on the electronic databases searched and criteria applied during assessment of studies for potential relevance to the review, please see the Methods section. Searching of electronic databases retrieved 197 studies. After deduplication and removal of conference abstracts, 110 records were screened for inclusion in the review. Appraisal of titles and abstracts led to the exclusion of 73 studies and the further review of 37 full publications. Of the 37 full articles evaluated, four systematic reviews and one RCT were included at this update.
Additional information
Analgesics are likely to be beneficial in children with AOM but current evidence is of low-quality. The benefits and harms of antibiotic treatment should be carefully balanced, especially since AOM symptoms settle spontaneously within 3 days in 80% of children. Antibiotics seem most effective in children aged less than 2 years with bilateral AOM and in children with AOM presenting with ear discharge.
About this condition
Definition
Otitis media, including acute otitis media (AOM) and otitis media with effusion (OME, also known as 'glue ear'), is one of the most common childhood conditions. While closely related, AOM and OME are two different, distinct conditions. AOM is characterised by the presence of middle-ear effusion together with an acute onset of signs and symptoms caused by middle ear inflammation. Symptoms of AOM include earache in older children; or pulling, tugging, or rubbing of the ear or non-specific symptoms such as fever, irritability, or poor feeding in younger children. AOM signs include a distinctly red, yellow, or cloudy tympanic membrane. AOM diagnosis is strengthened by the presence of a bulging tympanic membrane, an air-fluid level behind the tympanic membrane, tympanic membrane perforation, and/or discharge in the ear canal. Pneumatic otoscopy and/or tympanometry can be used to assess the presence (or absence) of middle ear effusion (MEE).In children with ventilation tubes (grommets) in place, ear discharge is a symptom of AOM whereby fluid that has built up in the middle ear drains through the tube into the child's ear canal. Interventions for ear discharge associated with ventilation tubes are beyond the scope of this review. While most children have occasional AOM episodes, an important subset suffer from recurrent AOM, defined as three or more episodes in 6 months or four episodes in 1 year. Middle ear effusion without signs of an acute infection indicates OME (see review on Otitis media with effusion), which can arise as a result of AOM, but can also occur independently. Chronic suppurative otitis media (CSOM, see review on CSOM) is characterised by continuing (>3 months) middle-ear inflammation and ear discharge through the tympanic membrane (perforation or ventilation tubes). Interventions for these conditions are assessed in separate reviews in Clinical Evidence (see review links above). For the purposes of this review, the age range used to define children is from birth to 15 years of age.
Incidence/
Prevalence
AOM is one of the most common childhood infections and an important reason for primary care visits in the UK. In the UK, antibiotics are prescribed for 87% of these episodes.
Aetiology/
Risk factors
The most common bacterial causes of AOM are Streptococcus pneumoniae, non-typeable Haemophilus influenzae, and Moraxella catarrhalis. There is increasing evidence that the predominant causative pathogen in AOM is changing from Streptococcus pneumoniae to non-typeable Haemophilus influenzae since the introduction of pneumococcal conjugate vaccines. Group childcare outside the home and passive smoking are thought to be the most important risk factors for AOM. Other risk factors include pacifier use and positive family history of AOM. Breastfeeding for 3 months or longer has a protective effect.
Prognosis
Without antibiotic treatment, AOM symptoms improve in 24 hours in 60% of children, and symptoms settle spontaneously within 3 days in 80% of children. Serious complications of AOM include acute mastoiditis, meningitis, and, rarely, intracranial complications. If antibiotics are withheld, acute mastoiditis occurs in about 1 to 2 per 10,000 children.
Aims of
intervention
To reduce the severity and duration of pain and other AOM-related symptoms; to prevent complications; to minimise adverse effects of treatment.
Outcomes
Symptoms of AOM (including earache [which can be assessed in young children by surrogate measures such as parental observation of distress/crying and analgesic use] and fever); recurrence of infection; complications of infection (including acute mastoiditis, meningitis, intracranial complications, and hearing problems due to middle-ear fluid [which can be assessed by surrogate measures such as abnormal tympanometry findings]), adverse effects.
Methods
Clinical Evidence search and appraisal October 2013. The following databases were used to identify studies for this systematic review: Medline 1966 to October 2013, Embase 1980 to October 2013, and The Cochrane Database of Systematic Reviews 2013, issue 9 (online; 1966 to date of issue). Additional searches were carried out in the Database of Abstracts of Reviews of Effects (DARE) and Health Technology Assessment (HTA) Database. We also searched for retractions of studies included in the review. Titles and abstracts identified by the initial search, run by an information specialist, were assessed against predefined criteria by an evidence analyst. Studies selected for inclusion were discussed with an expert contributor. All data relevant to the review were then extracted by an evidence analyst. Study design criteria for inclusion in this review were: published RCTs and systematic reviews of RCTs, at least single-blinded and containing more than 20 individuals, of whom more than 80% were followed up. There was no minimum length of follow-up. We excluded all studies described as 'open', 'open label', or not blinded, unless blinding was impossible. We included RCTs and systematic reviews of RCTs where harms of an included intervention were assessed, applying the same study design criteria for inclusion as we did for benefits. In addition, we use a regular surveillance protocol to capture harms alerts from organisations such as the FDA and the MHRA, which are added to the reviews as required. To aid readability of the numerical data in our reviews, we round many percentages to the nearest whole number. Readers should be aware of this when relating percentages to summary statistics such as relative risks (RRs) and odds ratios (ORs). We have performed a GRADE evaluation of the quality of evidence for interventions included in this review (see table). The categorisation of the quality of the evidence (high, moderate, low, or very low) reflects the quality of evidence available for our chosen outcomes in our defined populations of interest. These categorisations are not necessarily a reflection of the overall methodological quality of any individual study, because the Clinical Evidence population and outcome of choice may represent only a small subset of the total outcomes reported, and population included, in any individual trial. For further details of how we perform the GRADE evaluation and the scoring system we use, please see our website (www.clinicalevidence.com).
Table.
GRADE Evaluation of interventions for Acute otitis media in children.
Important outcomes
Complications, Recurrence, Symptoms of AOM
Studies (Participants)
Outcome
Comparison
Type of evidence
Quality
Consistency
Directness
Effect size
GRADE
Comment
What are the effects of treatments (analgesics, antibiotics, and myringotomy) in children with AOM?
2 (117)
Symptoms of AOM
Topical anaesthetic drops versus placebo
4
–1
0
–1
0
Low
Quality point deducted for sparse data; directness point deducted for inclusion of studies that included oral analgesics
1 (219)
Symptoms of AOM
Oral analgesics versus placebo
4
–1
0
–1
0
Low
Quality point deducted for incomplete reporting of results; directness point deducted for uncertain validity of outcome assessment
at least 17 (at least 4073)
Symptoms of AOM
Antibiotics versus placebo
4
0
–1
–1
0
Low
Consistency point deducted for conflicting results; directness point deducted for variation in diagnostic/entry criteria
6 (2200)
Recurrence
Antibiotics versus placebo
4
0
0
–1
0
Moderate
Directness point deducted for variation in diagnostic/entry criteria
at least 7 (at least 2114)
Complications
Antibiotics versus placebo
4
0
0
–1
0
Moderate
Directness point deducted for variation in diagnostic/entry criteria
at least 28 (at least 4910)
Symptoms of AOM
Different antibiotics versus each other
4
–2
0
–1
0
Very low
Quality points deducted for incomplete reporting of results and composite outcome measures; directness point deducted for clinical heterogeneity among RCTs
2 (498)
Symptoms of AOM
Immediate versus delayed antibiotic treatment
4
0
–1
0
0
Moderate
Consistency point deducted for conflicting results
27 (6727)
Symptoms of AOM
Longer versus shorter course of antibiotics
4
0
0
0
0
High
1 (171)
Symptoms of AOM
Myringotomy versus no myringotomy
4
–2
0
0
0
Low
Quality points deducted for sparse data and incomplete reporting of results
3 (821)
Symptoms of AOM
Myringotomy versus antibiotics
4
–1
–1
0
0
Low
Quality point deducted for incomplete reporting of results; consistency point deducted for conflicting results
We initially allocate 4 points to evidence from RCTs, and 2 points to evidence from observational studies. To attain the final GRADE score for a given comparison, points are deducted or added from this initial score based on preset criteria relating to the categories of quality, directness, consistency, and effect size.
Quality: based on issues affecting methodological rigour (e.g., incomplete reporting of results, quasi-randomisation, sparse data [<200 people in the analysis]).
Consistency: based on similarity of results across studies.
Directness: based on generalisability of population or outcomes.
Effect size: based on magnitude of effect as measured by statistics such as relative risk, odds ratio, or hazard ratio.
Glossary
High-quality evidence
Further research is very unlikely to change our confidence in the estimate of effect.
Low-quality evidence
Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.
Mastoiditis
The presence of infection in the mastoid cavity.
Moderate-quality evidence
Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.
Myringotomy
The surgical creation of a perforation in the tympanic membrane.
Very low-quality evidence
Any estimate of effect is very uncertain.
See Chronic suppurative otitis media
See Otitis media with effusion
Disclaimer
The information contained in this publication is intended for medical professionals. Categories presented in Clinical Evidence indicate a judgement about the strength of the evidence available to our contributors prior to publication and the relevant importance of benefit and harms. We rely on our contributors to confirm the accuracy of the information presented and to adhere to describe accepted practices. Readers should be aware that professionals in the field may have different opinions. Because of this and regular advances in medical research we strongly recommend that readers' independently verify specified treatments and drugs including manufacturers' guidance. Also, the categories do not indicate whether a particular treatment is generally appropriate or whether it is suitable for a particular individual. Ultimately it is the readers' responsibility to make their own professional judgements, so to appropriately advise and treat their patients.
To the fullest extent permitted by law, BMJ Publishing Group Limited and its editors are not responsible for any losses, injury or damage caused to any person or property (including under contract, by negligence, products liability or otherwise) whether they be direct or indirect, special, incidental or consequential, resulting from the application of the information in this publication.
Contributor Information
Roderick P. Venekamp, Department of Otorhinolaryngology and Julius Centre for Health Sciences and Primary Care, University Medical Centre, Utrecht, The Netherlands.
Roger A.M.J. Damoiseaux, Julius Centre for Health Sciences and Primary Care, University Medical Centre, Utrecht, The Netherlands.
Anne G.M. Schilder, evidENT at Ear Institute, University College London, London, UK.
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Analgesics (paracetamol, non-steroidal anti-inflammatory drugs [NSAIDs], and topical anaesthetic ear drops) may reduce earache compared with placebo.
Benefits and harms
Topical anaesthetic drops versus placebo:
We found one systematic review (search date 2011, 2 RCTs).
Symptoms of AOM
Topical anaesthetic drops compared with placebo Topical anaesthetic drops may be more effective at reducing earache 10 to 30 minutes after administration in children taking paracetamol (low-quality evidence).
Ref (type)
Population
Outcome, Interventions
Results and statistical analysis
Effect size
Favours
Pain
Systematic review
117 people, aged 3–19 years 2 RCTs in this analysis
25% reduction in earache
10 minutes after administration
37/58 (64%) with topical anaesthetic drops 25/59 (42%) with placebo
RR 1.51
95% CI 1.06 to 2.15
P = 0.02
NNT 4
95% CI 3 to 27
Small effect size
topical anaesthetic drops
Systematic review
117 people, aged 3–19 years 2 RCTs in this analysis
25% reduction in earache
20 minutes after administration
46/58 (79%) with topical anaesthetic drops 35/59 (59%) with placebo
RR 1.34
95% CI 1.04 to 1.71
P = 0.02
NNT 5
95% CI 3 to 27
Small effect size
topical anaesthetic drops
Systematic review
117 people, aged 3–19 years 2 RCTs in this analysis
25% reduction in earache
30 minutes after administration
54/58 (93%) with topical anaesthetic drops 41/59 (69%) with placebo
RR 1.34
95% CI 1.12 to 1.61
P <0.002
NNT 5
95% CI 3 to 10
Small effect size
topical anaesthetic drops
Systematic review
117 people, aged 3–19 years 2 RCTs in this analysis
50% reduction in earache
10 minutes after administration
25/58 (43%) with topical anaesthetic drops 12/59 (20%) with placebo
RR 2.13
95% CI 1.19 to 3.80
P = 0.01
NNT 4
95% CI 3 to 16
Moderate effect size
topical anaesthetic drops
Systematic review
117 people, aged 3–19 years 2 RCTs in this analysis
50% reduction in earache
20 minutes after administration
34/58 (59%) with topical anaesthetic drops 28/59 (47%) with placebo
RR 1.24
95% CI 0.88 to 1.74
P = 0.22
Not significant
Systematic review
117 people, aged 3–19 years 2 RCTs in this analysis
50% reduction in earache
30 minutes after administration
49/58 (84%) with topical anaesthetic drops 35/59 (59%) with placebo
RR 1.43
95% CI 1.12 to 1.81
P = 0.003
NNT 4
95% CI 3 to 11
No data from the following reference on this outcome.
Complications
No data from the following reference on this outcome.
Adverse effects
Ref (type)
Population
Outcome, Interventions
Results and statistical analysis
Effect size
Favours
Adverse effects
Systematic review
63 people, aged 3–19 years Data from 1 RCT
Adverse effects
with topical anaesthetic drops with placebo
One RCT in the review reported on adverse effects
The review reported that 3 people (treatment arm not specified) had mild dizziness that required no further treatment
All participants also received paracetamol
See Further information on studies for full details of co-interventions
We found one RCT comparing the effects of treatment with ibuprofen or paracetamol three times daily versus placebo for 48 hours.
Symptoms of AOM
Oral analgesics compared with placebo Oral ibuprofen or paracetamol may be more effective at reducing pain after 48 hours in children taking antibiotics (low-quality evidence).
Ref (type)
Population
Outcome, Interventions
Results and statistical analysis
Effect size
Favours
Pain
RCT
219 children, aged 1–6 years, with otoscopically diagnosed AOM and receiving antibiotic treatment with cefaclor for 7 days
Incidence of earache
2 days
5/71 (7%) with ibuprofen 19/75 (25%) with placebo
P <0.01
Effect size not calculated
ibuprofen
RCT
219 children, aged 1–6 years, with otoscopically diagnosed AOM and receiving antibiotic treatment with cefaclor for 7 days
Incidence of earache
2 days
7/73 (10%) with paracetamol 19/75 (25%) with placebo
The review included studies in which participants were also given oral analgesics. It is, therefore, difficult to properly assess the real effects of the anaesthetic ear drops.
The evidence from this RCT is limited because the assessment of the child's pain relief was based on parental observation using a scale of 0 or 1.
Comment
Drug safety alert
August 2013, paracetamol (acetaminophen)
The Food and Drug Administration (FDA) has issued a drug safety alert on the risk of rare but serious skin reactions with paracetamol (acetaminophen). These skin reactions, known as Stevens-Johnson Syndrome (SJS), toxic epidermal necrolysis (TEN), and acute generalised exanthematous pustulosis (AGEP), can be fatal.(www.fda.gov/)
Substantive changes
Analgesics (paracetamol, NSAIDs, topical anaesthetic ear drops) One systematic review updated. Categorisation unchanged (likely to be beneficial).
Antibiotics seem to reduce pain at 2 to 7 days and may reduce the rate of tympanic membrane perforation and development of contralateral otitis compared with placebo, but they increase the risks of vomiting, diarrhoea, and rash.
Antibiotics seem most effective in children aged less than 2 years with bilateral AOM and in children with AOM presenting with ear discharge.
Benefits and harms
Antibiotics versus placebo:
We found four systematic reviews (search dates 1997, 2005
, and 2012).
Symptoms of AOM
Antibiotics compared with placebo Antibiotics may be more effective at reducing pain and other symptoms of AOM after 2 to 7 days (low-quality evidence).
Ref (type)
Population
Outcome, Interventions
Results and statistical analysis
Effect size
Favours
Symptoms of AOM
Systematic review
1394 children, aged 12 years and younger 6 RCTs in this analysis
Pain outcomes
24 hours
267/709 (38%) with antibiotics 292/685 (43%) with placebo
RR 0.89
95% CI 0.78 to 1.01
Not significant
Systematic review
2320 children, aged 12 years and younger 7 RCTs in this analysis
Pain
at 2–3 days
138/1186 (12%) with antibiotics 180/1134 (16%) with placebo
RR 0.70
95% CI 0.57 to 0.86
Small effect size
antibiotics
Systematic review
1263 children, aged 12 years and younger 7 RCTs in this analysis
Pain
at 4–7 days
119/638 (17%) with antibiotics 154/625 (25%) with placebo
RR 0.79
95% CI 0.66 to 0.95
Small effect size
antibiotics
Systematic review
741 children, aged <2 years 4 RCTs in this analysis
Symptomatic improvement
7 days
357/416 (86%) with antibiotics 277/325 (85%) with placebo alone or versus placebo plus myringotomy
OR 1.31 (weighted OR, Mantel-Haenszel)
95% CI 0.83 to 2.08
Not significant
Systematic review
273 children, aged <2 years, with bilateral AOM 6 RCTs in this analysis Subgroup analysis
Pain, fever, or both
3–7 days
42/140 (30%) with antibiotics 74/133 (55%) with placebo
RR 0.64
95% CI 0.62 to 0.80
The differences for children aged <2 years with unilateral AOM and children aged >2 years with unilateral or bilateral AOM were not significant
Small effect size
antibiotics
Systematic review
116 children, aged 6 months–12 years, presenting with ear discharge 6 RCTs in this analysis Subgroup analysis
Pain, fever, or both
3–7 days
12/50 (24%) with antibiotics 39/66 (60%) with placebo
No data from the following reference on this outcome.
Recurrence
Antibiotics compared with placebo Antibiotics are no more effective at reducing the rate of recurrence in children with AOM (moderate-quality evidence).
Ref (type)
Population
Outcome, Interventions
Results and statistical analysis
Effect size
Favours
Recurrence
Systematic review
2200 children, aged 12 years and younger 6 RCTs in this analysis
Recurrence
208/1138 (18%) with antibiotics 213/1062 (20%) with placebo
No data from the following reference on this outcome.
Complications
Antibiotics compared with placebo Antibiotics seem no more effective at reducing the risk of abnormal tympanometry at 1 and 3 months in children with AOM, but seem to be associated with a lower rate of tympanic membrane perforation and contralateral otitis media (in unilateral cases) (moderate-quality evidence).
Ref (type)
Population
Outcome, Interventions
Results and statistical analysis
Effect size
Favours
Complications
Systematic review
2114 children, aged 12 years and younger 7 RCTs in this analysis
Abnormal tympanometry
at 4–6 weeks
438/1063 (41%) with antibiotics 472/1051 (24%) with placebo
RR 0.92
95% CI 0.83 to 1.01
Not significant
Systematic review
809 children, aged 12 years and younger 3 RCTs in this analysis
Abnormal tympanometry
at 3 months
96/411 (23%) with antibiotics 96/398 (24%) with placebo
RR 0.97
95% CI 0.76 to 1.24
Not significant
Systematic review
1328 children, aged 6 months–12 years 5 RCTs in this analysis
Abnormal tympanometry
1 month
47% with antibiotics 51% with placebo or no treatment Absolute numbers not reported
RR 0.93
95% CI 0.82 to 1.04
Not significant
Systematic review
1003 chldren, aged 6 months–10 years 4 RCTs in this analysis
Tympanic membrane perforation
9/491 (1.8%) with antibiotics 26/500 (5.2%) with placebo
RR 0.37
95% CI 0.18 to 0.76
P = 0.0069
Moderate effect size
antibiotics
Systematic review
974 children, aged 6 months–15 years 4 RCTs in this analysis
Contralateral otitis (in unilateral cases)
48/453 (10.6%) with antibiotics 85/453 (18.8%) with placebo
No data from the following reference on this outcome.
Further information on studies
This systematic review compared antibiotics with placebo. It found one case of mastoiditis in each treatment group, but from different RCTs. No further analysis of this outcome was reported.
Three RCTs based diagnosis of AOM on otoscopic appearance of the tympanic membrane and clinical signs of acute infection, and one RCT based diagnosis on otoscopy findings alone.
Comment
The results of systematic reviews comparing antibiotics versus placebo vary owing to differences in entry criteria and outcome measures.
Certain RCTs have used more stringent diagnostic criteria for AOM compared with others, including different clinical and otoscopic signs with varying degrees of specificity. The authors of one systematic review highlighted the possibility of a blunting of antibiotic treatment effect where less stringent diagnostic criteria had been applied.
In addition, different trials used varying outcome measures. For instance, one systematic review focused on outcome measures felt to be more relevant to patients, such as relief of pain, rather than outcomes related to microbiological cure.
One of the included studies was an individual patient data meta-analysis. This showed more benefit from antibiotics compared with placebo in a subset of children aged under 2 years who had bilateral otitis media. It also showed more benefit from antibiotics in children who had both AOM and ear discharge compared with placebo. The analysis did not find a difference for age alone without the other clinical features mentioned.
Clinical guide:
Without antibiotic treatment, AOM symptoms settled spontaneously within 3 days in 80% of children.
The setting for different trials in time and place will produce variation in results. One quasi-randomised trial from Sweden conducted in 1954 compared the effects of antibiotics versus placebo. It found no cases of mastoiditis in the penicillin-treated group, whereas 17% of the control group developed mastoiditis. Therefore, in populations in which the incidence of complicating mastoiditis is high, antibiotic treatment would be advised. In contrast, an observational study from Denmark found that the incidence of acute mastoiditis remained stable over a 10-year period (from 1988–2007), despite the implementation of conservative management guidelines for the treatment of AOM in children.
Substantive changes
Antibiotics versus placebo Evidence re-evaluated. One systematic review updated. Categorisation unchanged (trade-off between benefits and harms).
We do not know whether any one antibiotic regimen should be used in preference to another, but amoxicillin may be more effective than macrolides and cephalosporin.
The local resistance pattern is also important when choosing the type of antibiotic.
NOTE Antibiotics increase the risk of vomiting, diarrhoea, and rash compared with placebo, but rates may vary between different types of antibiotic.
Benefits and harms
Different antibiotics versus each other:
We found three systematic reviews (search dates 1992, 2008, and 2010) and one subsequent RCT. Only the first two systematic reviews are reported here, as all of the RCTs included in the third systematic review are assessed in the first two systematic reviews.
Symptoms of AOM
Different antibiotics compared with each other Macrolide and cephalosporin antibiotics may be less effective than amoxicillin or amoxicillin-clavulanic acid (co-amoxiclav) at reducing signs and symptoms of AOM, while other antibiotics may be as effective as each other (very low-quality evidence).
Ref (type)
Population
Outcome, Interventions
Results and statistical analysis
Effect size
Favours
Symptoms of AOM
Systematic review
4580 children, aged 4 months to 18 years 27 RCTs in this analysis
Primary control defined as absence of any symptom or sign
7–14 days
with different antibiotics versus each other Absolute numbers not reported
P values not reported
Reported as not significant for all comparisons
Not significant
Systematic review
2766 children, aged 6 months to 15 years 10 RCTs in this analysis
Clinical failure
10–16 days
146/1371 (11%) with amoxicillin or amoxicillin-clavulanic acid 196/1395 (14%) with macrolide antibiotics
RR 1.31
95% CI 1.07 to 1.60
P = 0.008
Small effect size
amoxicillin or amoxicillin–clavulanic acid
RCT
330 children, aged 6–24 months
Clinical cure
141/165 (86.5%) with amoxicillin/clavulanic acid 115/165 (71.0%) with cefdinir
No data from the following reference on this outcome.
Further information on studies
AOM was defined as bulging or opacification of the tympanic membrane with or without erythema, accompanied by at least one sign (fever, earache, irritability, otorrhoea, lethargy, anorexia, vomiting, diarrhoea, poor or absent mobility of the tympanic membrane). Treatment success was defined as absence of all presenting signs and symptoms of AOM at the evaluation point closest to 7 to 14 days after start of treatment.
AOM was diagnosed based on pneumatic otoscopy and an abnormal tympanogram. Symptoms of earache, irritability, anorexia, and fever were assessed at diagnosis. Clinical outcome was assessed 12 to 15 days after start of treatment and was classified as clinical cure (composite outcome of absence of fever, improved otoscopic signs, absence of surgery for AOM), clinical failure (composite outcome: antibiotic prescription or surgery for AOM, no improvement of otoscopic signs, presence of tympanic membrane perforation, or subject had unsatisfactory resolution of signs and symptoms of AOM according to investigator), or indeterminate (<80% of prescribed treatment was taken or inadequate data due to lack of follow-up; those subjects were not included in the analysis).
Comment
Clinical guide:
Many RCTs have studied a variety of antibiotic regimens for the treatment of otitis media, but there is heterogeneity in participants, treatment regimens, controls, and outcome measures. The local resistance pattern is also important when choosing the type of antibiotic.
Substantive changes
Type of antimicrobial agent (antibiotic regimen) Title of option changed from 'Choice of antibiotic regimen' to 'Type of antimicrobial agent (antibiotic regimen)'. One systematic review updated, one RCT added. Categorisation unchanged (trade-off between benefits and harms).
Immediate use of antibiotics may provide short-term reduction for some symptoms of AOM, but it increases the risk of rash and diarrhoea compared with delayed treatment.
Benefits and harms
Immediate versus delayed antibiotic treatment:
We found one systematic review (search date 2013). Owing to heterogeneity among studies, the review did not perform meta-analyses. We, therefore, report data from individual RCTs.
Symptoms of AOM
Immediate antibiotics compared with delayed antibiotics Immediate antibiotics may be more effective at reducing pain and other symptoms of AOM at 3 days, but not after 7 days (moderate-quality evidence).
Ref (type)
Population
Outcome, Interventions
Results and statistical analysis
Effect size
Favours
Symptoms of AOM
Systematic review
212 children, aged 6 months–10 years Data from 1 RCT
Proportion of children with pain
3 days
28/111 (25%) with delayed antibiotics 15/101 (15%) with immediate antibiotics
OR 1.93
95% CI 0.96 to 3.88
Not significant
Systematic review
212 children, aged 6 months–10 years Data from 1 RCT
Proportion of children with pain
7 days
3/111 (3%) with delayed antibiotics 0/101 (0%) with immediate antibiotics
OR 6.55
95% CI 0.33 to 128.34
Not significant
Systematic review
285 children, aged 6 months–10 years Data from 1 RCT
Proportion of children with malaise
3 days
45/150 (30%) with delayed antibiotics 19/135 (14%) with immediate antibiotics
OR 2.62
95% CI 1.44 to 4.76
Moderate effect size
immediate antibiotics
Systematic review
213 children, aged 6 months–10 years Data from 1 RCT
Mean pain severity
3 days
2.56 with delayed antibiotics 1.81 with immediate antibiotics
Mean difference 0.75
95% CI 0.26 to 1.24
Effect size not calculated
immediate antibiotics
Systematic review
212 children, aged 6 months–10 years Data from 1 RCT
Mean pain severity
7 days
1.17 with delayed antibiotics 1.05 with immediate antibiotics
Mean difference +0.12
95% CI –0.04 to +0.28
Not significant
Systematic review
282 children, aged 6 months–12 years Data from 1 RCT
Mean number of spoons of paracetamol/day
2.28 with delayed antibiotics 1.69 with immediate antibiotics
Mean difference 0.59
95% CI 0.25 to 0.93
Effect size not calculated
immediate antibiotics
Systematic review
265 children, aged 6 months–12 years Data from 1 RCT
Fever
days 4–6
42/132 (32%) with delayed antibiotics 46/133 (35%) with immediate antibiotics
OR 0.88
95% CI 0.53 to 1.47
Not significant
Systematic review
265 children, aged 6 months–12 years Data from 1 RCT
Proportion of children with pain
days 4–6
85/132 (64%) with delayed antibiotics 89/133 (67%) with immediate antibiotics
OR 0.89
95% CI 0.54 to 1.48
Not significant
Systematic review
265 children, aged 6 months–12 years Data from 1 RCT
Use of paracetamol or ibuprofen
123/132 (93%) with delayed antibiotics 120/133 (90%) with immediate antibiotics
OR 1.48
95% CI 0.61 to 3.59
Not significant
Systematic review
265 children, aged 6 months to 12 years Data from 1 RCT
Re-consultation rate
13/132 (10%) with delayed antibiotics 11/133 (8%) with immediate antibiotics
Prescribing delayed antibiotics, using a prescription to be filled later if symptoms do not improve, is a tool for the physician to reduce antibiotic use rather than a treatment option for AOM. If antibiotics have a small effect on the outcome of AOM, then this effect will clearly apply to immediate antibiotics. Because the evidence suggests that antibiotics should only be prescribed to certain subgroups of patients (children aged <2 years with bilateral AOM and children with AOM presenting with ear discharge), physicians should discuss the wait-and-see policy with parents of children not in those subgroups. A delayed prescription should be provided with care, since oral antibiotics may not be the best option in very young children with worsening symptoms. In these cases the physician and not the parents of the child should make the decision about whether to give antibiotics and in which setting. In most developed countries, it is relatively easy for parents to re-consult a physician when symptoms either do not improve or get worse.
One study in the review showed no difference in re-consultation rate between the two groups. One study comparing delayed antibiotics versus no antibiotics showed no difference in the outcomes of pain and fever.
Substantive changes
Immediate versus delayed antibiotic treatment One systematic review updated. Categorisation unchanged (trade-off between benefits and harms).
Longer courses of antibiotics reduce short-term treatment failure, but have no benefit over the longer term compared with shorter regimens.
Benefits and harms
Longer versus shorter course of antibiotics:
We found one systematic review (search date 2009).
Symptoms of AOM
Longer courses of antibiotics compared with shorter courses Longer (8–10 days) courses of antibiotics are more effective at reducing symptoms and preventing relapse or re-infection at 8 to 19 days compared with 7-day courses, but are no more effective than shorter courses after 20 to 30 days (high-quality evidence).
Ref (type)
Population
Outcome, Interventions
Results and statistical analysis
Effect size
Favours
Symptoms of AOM
Systematic review
5093 children, aged between 4 weeks–15 years 16 RCTs in this analysis
Treatment failure
1 month or less
486/2376 (20%) with short-course antibiotics (<7 days) 475/2717 (17%) with longer-course antibiotics (8–10 days)
OR 1.34
95% CI 1.15 to 1.55
P = 0.0001
Small effect size
longer-course antibiotics
Systematic review
3932 children, aged between 4 weeks–15 years 11 RCTs in this analysis
Treatment failure
8–19 days
340/1892 (18%) with short-course antibiotics (<7 days) 293/2040 (14%) with longer-course antibiotics (8–10 days)
OR 1.37
95% CI 1.15 to 1.64
P = 0.0004
Small effect size
longer-course antibiotics
Systematic review
2475 children, aged between 4 weeks–15 years 9 RCTs in this analysis
Treatment failure
20–30 days
238/1141 (21%) with short-course antibiotics (<7 days) 271/1335 (20%) with longer-course antibiotics (8–10 days)
OR 1.16
95% CI 0.94 to 1.42
Not significant
Systematic review
2068 children, aged between 4 weeks–15 years 7 RCTs in this analysis
Treatment failure
3 months or less
391/973 (40%) with short-course antibiotics (<7 days) 399/1095 (36%) with longer-course antibiotics (8–10 days)
OR 1.18
95% CI 0.98 to 1.41
Not significant
Systematic review
570 children, aged between 4 weeks–2 years 5 RCTs in this analysis
Treatment failure
1 month or less
99/296 (33%) with short-course antibiotics (<7 days) 85/274 (31%) with longer-course antibiotics (8–10 days)
OR 1.09
95% CI 0.76 to 1.57
Not significant
Systematic review
1064 children, aged between 2 years–15 years 6 RCTs in this analysis
Treatment failure
1 month or less
74/530 (14%) with short-course antibiotics (<7 days) 86/534 (16%) with longer-course antibiotics (8–10 days)
Treatment failure was defined as lack of clinical resolution, relapse, or recurrence of AOM during a 1-month period following the initiation of therapy. Clinical resolution was defined as improved or resolving signs or symptoms of AOM. Treatment failure at 3 months was defined as relapses and recurrences up to 3 months.
Comment
A subgroup analysis showed that children aged under 2 years had no benefit from longer courses of antibiotics compared with shorter courses. In addition, they had a greater risk of treatment failure compared with older children irrespective of treatment duration.
Myringotomy may be less effective than antibiotics at reducing symptoms, and we found no evidence that it was superior to no myringotomy.
Benefits and harms
Myringotomy versus no myringotomy:
We found one RCT.
Symptoms of AOM
Myringotomy compared with no myringotomy Myringotomy may be no more effective than no myringotomy at reducing the symptoms of AOM after 1 to 7 days (low-quality evidence).
Ref (type)
Population
Outcome, Interventions
Results and statistical analysis
Effect size
Favours
Symptoms of AOM
RCT 4-armed trial
171 children, aged 2–12 years with AOM
Pain
24 hours
26/36 (72.2%) with myringotomy only 29/40 (72.5%) with no treatment
P value not reported
Reported as not significant for myringotomy v no treatment
Not significant
RCT 4-armed trial
171 children, aged 2–12 years with AOM
Pain
7 days
31/35 (89%) with myringotomy only 34/38 (90%) with no treatment
P value not reported
Reported as not significant for myringotomy v no treatment
No data from the following reference on this outcome.
Further information on studies
The RCT gave results in the form of children or as individual ears as the unit measured. Because randomisation was based on children, the figures reported here exclude those results based on individual ears.
AOM was defined as the presence of middle-ear effusion and bulging (with or without redness) of the tympanic membrane associated with recent irritability or fever. The RCT gave results in the form of children or as individual ears as the unit measured. Because randomisation was based on children, the figures reported here exclude those results based on individual ears.
AOM was diagnosed on the basis of fever, ear pain, or irritability with redness and/or bulging of the eardrum. An episode of AOM was classified as severe or non-severe according to the child's temperature and an ear pain score.
