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Amoxicillin treatment increases rate of late recurrence of acute otitis media in young children
Translating Best Evidence into Best Care EDITOR’S NOTE: Journals reviewed for this issue: Archives of Disease in Childhood, Archives of Pediatrics and Adolescent Medicine, British Medical Journal, Journal of the American Medical Association, The Journal of Pediatrics, The Lancet, New England Journal of Medicine, Pediatric Infectious Diseases Journal, and Pediatrics. Heidi Marleau, MLS, Ebling Library for the Health Sciences, University of Wisconsin, contributed to the review and selection of this month’s abstracts. —John G. Frohna, MD, MPH
Amoxicillin treatment increases rate of late recurrence of acute otitis media in young children 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. 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? Design Prospective 3-year follow-up study within the framework of a primary care–based, double-blind, randomized, placebo-controlled trial. Setting A total of 53 general practices in the Netherlands. Participants A total of 168 children aged 6 months to 2 years with acute otitis media. 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. Outcomes Recurrence of acute otitis media; referral to secondary care; ear, nose, and throat surgery. 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%). 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. 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 follow-up. This report will, however, fuel discussions calling for watchful waiting without the use of antibiotics in noncomplicated acute childhood otitis media. Petri S. Mattila, MD, PhD Department of Otorhinolaryngology Helsinki University Central Hospital Helsinki, Finland
References 1. Damoiseaux RA, van Balen FA, Hoes AW, Verheij TJ, de Melker RA. Primary care based randomised, double blind trial of amoxicillin versus placebo for acute otitis media in children aged under 2 years. BMJ 2000;320:350-4. 2. Damoiseaux RA, Rovers MM, Van Balen FA, Hoes AW, de Melker RA. Long-term prognosis of acute otitis media in infancy: determinants of recurrent acute otitis media and persistent middle ear effusion. Family Practice 2006;23:40-5. 3. Damoiseaux RA. Otitis media. Lancet 2004;363:1324. 163
Amoxicillin treatment increases rate of late recurrence of acute otitis media in young children 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. 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? Design Prospective 3-year follow-up study within the framework of a primary care–based, double-blind, randomized, placebo-controlled trial. Setting A total of 53 general practices in the Netherlands. Participants A total of 168 children aged 6 months to 2 years with acute otitis media. 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. Outcomes Recurrence of acute otitis media; referral to secondary care; ear, nose, and throat surgery. 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%). 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. 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 follow-up. This report will, however, fuel discussions calling for watchful waiting without the use of antibiotics in noncomplicated acute childhood otitis media. Petri S. Mattila, MD, PhD Department of Otorhinolaryngology Helsinki University Central Hospital Helsinki, Finland
References 1. Damoiseaux RA, van Balen FA, Hoes AW, Verheij TJ, de Melker RA. Primary care based randomised, double blind trial of amoxicillin versus placebo for acute otitis media in children aged under 2 years. BMJ 2000;320:350-4. 2. Damoiseaux RA, Rovers MM, Van Balen FA, Hoes AW, de Melker RA. Long-term prognosis of acute otitis media in infancy: determinants of recurrent acute otitis media and persistent middle ear effusion. Family Practice 2006;23:40-5. 3. Damoiseaux RA. Otitis media. Lancet 2004;363:1324. 163