Amoxicillin treatment increases rate of late

recurrence of acute otitis media in young

children
Petri S. Mattila
, MD, PhD

Department of Otorhinolaryngology, Helsinki University Central Hospital, Helsinki, Finland

DOI: http://dx.doi.org/10.1016/j.jpeds.2009.09.057
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Article Outline
1.

Question

2.

Design

3.

Setting

4.

Participants

5.

Intervention

6.

Outcomes

7.

Main Results

8.

Conclusions

9.

Commentary

Bezakova N, Damoiseaux RA, Hoes AW, Schilder AG, Rovers MM. Recurrence up to 3.5 years after antibiotic
treatment of acute otitis media in very young Dutch children: survey of trial participants. BMJ 2009;338:b2525.
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Question

In young children with acute otitis media who are treated with antibiotics, what is the likelihood of recurrence, the
need for referral to secondary care, and the need for ear, nose, and throat surgery?
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Design
Prospective 3-year follow-up study within the framework of a primary carebased, double-blind, randomized,
placebo-controlled trial.
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Setting
A total of 53 general practices in the Netherlands.
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Participants
A total of 168 children aged 6 months to 2 years with acute otitis media.
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Intervention
Amoxicillin 40 mg/kg/d in 3 doses compared with placebo. Three years after the intervention, a questionnaire was
sent asking the parents about episodes of recurrent otitis media, referral to secondary care, and ear, nose, and
throat surgery.
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Outcomes
Recurrence of acute otitis media; referral to secondary care; ear, nose, and throat surgery.
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Main Results
Seventy percent of the parents returned the questionnaire. Acute otitis media recurred in 63% (47/75) of children
in the amoxicillin group and in 43% (37/86) of the placebo group (risk difference 20%, 95% confidence interval
5% to 35%, number needed to harm = 5); 30% (24/78 amoxicillin; 27/89 placebo) of children in both groups were
referred to secondary care, and 21% (16/78) of the amoxicillin group compared with 30% (27/90) of the placebo
group had ear, nose, and throat surgery (risk difference 9%, 23% to 4%).
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Conclusions

For every 5 children treated with amoxicillin, 1 will have an episode of recurrent acute otitis media. This is another
argument for judicious use of antibiotics in children with acute otitis media.
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Commentary
This study reports long-term outcomes of a trial on the effect of amoxicillin in acute otitis media. The results after
6 weeks,1 6 months,2 and a preliminary report of the 3-year follow-up have previously been reported.3 During the
6-week follow-up, amoxicillin relieved acute symptoms of otitis media.1 After the 6-month follow-up, there was no
difference in the recurrence of otitis media between the randomization groups. The surprising finding was that
between 6 months and 3 years after the intervention, children who had initially received amoxicillin for 3 days had
recurrent otitis media more often than children who had received placebo. The authors discuss that antibiotic
treatment might result in an impaired immune response to otitis media pathogens or to unfavorable alterations in
nasopharyngeal colonization. The authors acknowledge that these mechanisms should probably influence the
rate of otitis media recurrence during the first 6 months of follow-up, which was not the case. In addition, of note is
that it was not reported how many courses of antibiotics the children had received before the intervention with
amoxicillin or placebo, or how often and what antibiotics were prescribed to the children during the first 6 months
of the follow-up, when there was 50% recurrence of otitis media in the amoxicillin group, as well as in the placebo
group. The observation of the late effect of amoxicillin treatment remains unexplained and is so far the only report
that shows such adverse late effects in otitis media. Clearly, the report calls for further investigations of the late
effects of antibiotic treatments. On the other hand, it should be noted that in this study population, acute
symptoms of otitis media were relieved during the first week immediately after amoxicillin treatment and that
amoxicillin did not increase referral to secondary care or surgery related to otitis media during the 3-year followup. This report will, however, fuel discussions calling for watchful waiting without the use of antibiotics in
noncomplicated acute childhood otitis media.
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References
1Damoiseaux, R.A., van Balen, F.A., Hoes, A.W., Verheij, T.J., and de Melker, R.A. Primary care based
randomised, double blind trial of amoxicillin versus placebo for acute otitis media in children aged
under 2 years. BMJ. 2000; 320: 350354
o

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2Damoiseaux, R.A., Rovers, M.M., Van Balen, F.A., Hoes, A.W., and de Melker, R.A. Long-term prognosis
of acute otitis media in infancy: determinants of recurrent acute otitis media and persistent middle ear
effusion. Family Practice. 2006; 23: 4045

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3Damoiseaux, R.A. Otitis media. Lancet. 2004; 363: 1324