antibiotic use or placebo for ear infection - recurrence evaluation

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http://www.bmj.com/cgi/content/full/338/jun30_1/b2525

Published 30 June 2009, doi:10.1136/bmj.b2525

*Cite this as:* BMJ 2009;338:b2525

Recurrence up to 3.5 years after antibiotic treatment of acute

otitis media in very young Dutch children: survey of trial

participants

*Natália Bezáková*, /medical student/^1 , * A M J Damoiseaux*,

/general practitioner/^2 , *Arno W Hoes*, /professor of clinical

epidemiology and general practice/^1 , *Anne G M Schilder*,

/otorhinolaryngologist and clinical epidemiologist/^3 , *Maroeska M

Rovers*, /clinical epidemiologist/^1

^1 Julius Center for Health Sciences and Primary Care, University

Medical Center Utrecht, PO Box 85060, 3508 AB Utrecht, Netherlands, ^2

General Practice de Hof van Blom, 8051 JT Hattem, Netherlands, ^3

Department of Otorhinolaryngology, Wilhelmina Children’s Hospital,

University Medical Center Utrecht

Correspondence to: M M Rovers m.rovers@...

Abstract

Abstract

Introduction

<http://www.bmj.com/cgi/content/full/338/jun30_1/b2525#SEC1> Methods

<http://www.bmj.com/cgi/content/full/338/jun30_1/b2525#SEC2> Results

<http://www.bmj.com/cgi/content/full/338/jun30_1/b2525#SEC3> Discussion

<http://www.bmj.com/cgi/content/full/338/jun30_1/b2525#SEC4> References

<http://www.bmj.com/cgi/content/full/338/jun30_1/b2525#BIBL>

*Objective* To determine the long term effects of antibiotic treatment^

for acute otitis media in young children.^

*Design* Prospective three year follow-up study within the framework^ of

a primary care based, double blind, randomised, placebo controlled^ trial.^

*Setting* 53 general practices in the Netherlands.^

*Participants* 168 children aged 6 months to 2 years with acute^ otitis

media.^

*Interventions* Amoxicillin 40 mg/kg/day in three doses compared^ with

placebo.^

*Main outcome measures* Recurrence of acute otitis media; referral^ to

secondary care; ear, nose, and throat surgery.^

*Results* 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%); 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%).^

*Conclusion* Recurrent acute otitis media occurred more often^ in the

children originally treated with amoxicillin. This is^ another argument

for judicious use of antibiotics in children^ with acute otitis media.^

*Trial registration* Netherlands Trial Register NTR1426.^

Introduction

Abstract

<http://www.bmj.com/cgi/content/full/338/jun30_1/b2525#ABS> Introduction

Methods

<http://www.bmj.com/cgi/content/full/338/jun30_1/b2525#SEC2> Results

<http://www.bmj.com/cgi/content/full/338/jun30_1/b2525#SEC3> Discussion

<http://www.bmj.com/cgi/content/full/338/jun30_1/b2525#SEC4> References

<http://www.bmj.com/cgi/content/full/338/jun30_1/b2525#BIBL>

Acute otitis media, one of the most common infections in childhood,^

remains the leading cause of doctors’ consultations by^ children and the

most common reason for children to take antibiotics.^1

<http://www.bmj.com/cgi/content/full/338/jun30_1/b2525#REF1> ^ Current

guidelines recommend prescription of antibiotics in^ children with

severe illness and in those younger than 2 years^ of age with bilateral

acute otitis media or acute otorrhoea.^ For most other children with

acute otitis media, initial observation^ is recommended.^2

<http://www.bmj.com/cgi/content/full/338/jun30_1/b2525#REF2> ^3

<http://www.bmj.com/cgi/content/full/338/jun30_1/b2525#REF3> ^4

<http://www.bmj.com/cgi/content/full/338/jun30_1/b2525#REF4> ^

So far, little is known about the long term effects of antibiotics^ in

acute otitis media. Initial prescription of antibiotics may^ on the one

hand shorten the course of acute otitis media.^5

<http://www.bmj.com/cgi/content/full/338/jun30_1/b2525#REF5> ^6

<http://www.bmj.com/cgi/content/full/338/jun30_1/b2525#REF6> ^ On the

other hand, it may encourage doctors’ attendance^ in future episodes,

increase pressure on doctors to prescribe,^ increase future use of

antibiotics, and therefore increase antibiotic^ resistance.^7

<http://www.bmj.com/cgi/content/full/338/jun30_1/b2525#REF7> ^8

<http://www.bmj.com/cgi/content/full/338/jun30_1/b2525#REF8> In

addition, antibiotic treatment may cause an^ unfavourable shift towards

colonisation with resistant pathogens,^ which are likely to promote

recurrence of the infection.^9

<http://www.bmj.com/cgi/content/full/338/jun30_1/b2525#REF9> ^10

<http://www.bmj.com/cgi/content/full/338/jun30_1/b2525#REF10> ^ ^11

<http://www.bmj.com/cgi/content/full/338/jun30_1/b2525#REF11> ^12

<http://www.bmj.com/cgi/content/full/338/jun30_1/b2525#REF12> We aimed

to study the long term effects of antibiotics^ on recurrence of acute

otitis media; referrals to secondary^ care; and ear, nose, and throat

surgery.^

Methods

Abstract

<http://www.bmj.com/cgi/content/full/338/jun30_1/b2525#ABS> Introduction

<http://www.bmj.com/cgi/content/full/338/jun30_1/b2525#SEC1> Methods

Results

<http://www.bmj.com/cgi/content/full/338/jun30_1/b2525#SEC3> Discussion

<http://www.bmj.com/cgi/content/full/338/jun30_1/b2525#SEC4> References

<http://www.bmj.com/cgi/content/full/338/jun30_1/b2525#BIBL>

We did the study within the framework of a primary care based,^

randomised, placebo controlled, double blind trial on the effects^ of

amoxicillin compared with placebo in children with acute^ otitis media

aged between 6 and 24 months.^5

<http://www.bmj.com/cgi/content/full/338/jun30_1/b2525#REF5> The

diagnosis of^ acute otitis media was based on the presence of acute

signs^ of infection and otoscopy. The original study took place in^ the

Netherlands between February 1996 and May 1998 and included^ 240

children, who were followed actively for six months.^5

<http://www.bmj.com/cgi/content/full/338/jun30_1/b2525#REF5> ^13

<http://www.bmj.com/cgi/content/full/338/jun30_1/b2525#REF13> ^ At trial

entry, parents were informed that treatment allocation^ would be

revealed only after the final follow-up, including^ the post-trial

period of about three years. Only in case of^ severe complications or

side effects would the treatment code^ be broken during the trial. The

results at days four and 11^ and at six months were reported in 2000 and

2006.^5 <http://www.bmj.com/cgi/content/full/338/jun30_1/b2525#REF5> ^13

<http://www.bmj.com/cgi/content/full/338/jun30_1/b2525#REF13> ^

In 2000—that is, approximately three and half years after^ the start of

the trial—we sent a questionnaire to parents^ of the participating

children, asking them about episodes of^ recurrent acute otitis media;

referral to secondary care; and^ ear, nose, and throat surgery. We

defined the primary outcome^ measure, reported recurrent acute otitis

media, as at least^ one episode of acute otitis media that occurred

between the^ last study appointment at six months and the current

survey.^ In addition, we compared the proportion of children referred^

to secondary care (paediatrician or ear, nose, and throat surgeon)^ and

the rate of ear, nose, and throat surgery.^

In the first instance, we looked only at risk difference and^ did not

adjust for potential confounders, as we were reporting^ on the long term

effects of a randomised placebo controlled^ trial. To be sure that

confounding was not a problem in the^ post-randomisation period, we also

studied the following potential^ confounders by using logistic

regression analysis: mean age^ at inclusion, sex, breast feeding, number

of siblings, season^ of inclusion, attendance at day care centre, family

history^ of recurrent upper respiratory tract infections, (duration of)^

symptoms at presentation, subsequent use of antibiotics within^ six

months, and the clinical outcome at days four and 11 and^ six months.^

Finally, we did a sensitivity analysis on the primary outcome^

restricted to the children in each group who did not receive^

antibiotics within the first six months of the post-trial follow-up^

period. We did all analyses with SPSS 14.0 on an intention to^ treat

basis.^

Results

Abstract

<http://www.bmj.com/cgi/content/full/338/jun30_1/b2525#ABS> Introduction

<http://www.bmj.com/cgi/content/full/338/jun30_1/b2525#SEC1> Methods

<http://www.bmj.com/cgi/content/full/338/jun30_1/b2525#SEC2> Results

Discussion

<http://www.bmj.com/cgi/content/full/338/jun30_1/b2525#SEC4> References

<http://www.bmj.com/cgi/content/full/338/jun30_1/b2525#BIBL>

Of the 240 participants originally randomised, 168 (70%) returned^ the

questionnaire. At this stage, about 95% of these parents^ were still

blinded to the original treatment. The baseline characteristics^ of

these 168 children were similar to those initially randomised^ (table

1Go <http://www.bmj.com/cgi/content/full/338/jun30_1/b2525#TBL1>).......^

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http://www.bmj.com/cgi/content/full/338/jun30_1/b2525