Effect of Antibiotics for Otitis Media on Mastoiditis in Children

<strong>Effect</strong> <strong>of</strong> <strong>Antibiotics</strong> <strong>for</strong> <strong>Otitis</strong> <strong>Media</strong> on Mastoiditis in Children: A Retrospective 

Cohort Study Using the United Kingdom General Practice Research Database 

Paula Louise Thompson, Ruth E. Gilbert, Paul F. Long, Sonia Saxena, Mike Sharland 

and Ian Chi Kei Wong 

Pediatrics 2009;123;424-430 

DOI: 10.1542/peds.2007-3349 

The online version <strong>of</strong> this article, along with updated in<strong>for</strong>mation and services, is 

located on the World Wide Web at: 

http://www.pediatrics.org/cgi/content/full/123/2/424 

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ARTICLE 

<strong>Effect</strong> <strong>of</strong> <strong>Antibiotics</strong> <strong>for</strong> <strong>Otitis</strong> <strong>Media</strong> on Mastoiditis 

in Children: A Retrospective Cohort Study Using the 

United Kingdom General Practice Research Database 

Paula Louise Thompson, BSc, MSc Epid a , Ruth E. Gilbert, MB ChB, MSc Epid, MD b , Paul F. Long, BSc, MSc, PhD (Cantab) a,c , 

Sonia Saxena, MBBS, MSc, MD, MRCGP d , Mike Sharland, FRCPCH, BSc, MD e , Ian Chi Kei Wong, BSc, MSc, PhD a 

a Centre <strong>for</strong> Paediatric Pharmacy Research and c Department <strong>of</strong> Pharmaceutics, School <strong>of</strong> Pharmacy, University <strong>of</strong> London, London, England; b Centre <strong>for</strong> Paediatric 

Epidemiology and Biostatistics, Institute <strong>of</strong> Child Health, London, England; d Department <strong>of</strong> Primary Care and Social Medicine, Imperial College, London, England; 

e Paediatric Infectious Diseases Unit, St George’s Hospital, London, England 

Financial Disclosure: Ms Thompson and Drs Gilbert, Sharland, and Wong were members <strong>of</strong> the UK Department <strong>of</strong> Health’s Specialist Advisory Committee on Antimicrobial Resistance (SACAR), pediatrics 

subgroup. Drs Long and Saxena have no financial relationships relevant to this article to disclose. 

What’s Known on This Subject 

Ecological studies <strong>of</strong> routine health care databases have suggested that the reduction in 

antibiotic prescribing to children may be associated with an increase in rare complications 

<strong>of</strong> bacterial infection, particularly mastoiditis after otitis media. Individual patientlevel 

analyses are now required. 

ABSTRACT 

What This Study Adds 

BACKGROUND. In<strong>for</strong>mation is needed on whether mastoiditis has increased in association 

with the decline in antibiotics prescribed to children by primary care physicians in 

the United Kingdom. 

OBJECTIVE. To determine time trends in mastoiditis incidence, the frequency <strong>of</strong> antecedent 

otitis media, and the effect <strong>of</strong> antibiotics <strong>for</strong> otitis media on the risk <strong>of</strong> 

mastoiditis in children. 

PATIENTS AND METHODS. We conducted a retrospective cohort study by using the UK 

General Practice Research Database. Children aged 3 months to 15 years between 

1990 and 2006 were included. Risk <strong>of</strong> mastoiditis within 3 months after otitis media 

diagnosis and the protective effect <strong>of</strong> antibiotics were determined. 

RESULTS. There were 2 622 348 children within the General Practice Research Database; 

854 had mastoiditis, only one third <strong>of</strong> whom (35.7%) had antecedent otitis 

media. Mastoiditis incidence remained stable between 1990 and 2006 (�1.2 per 

10 000 child-years). Risk <strong>of</strong> mastoiditis, after otitis media, was 1.8 per 10 000 

episodes (139 <strong>of</strong> 792 623) after antibiotics compared with 3.8 per 10 000 (149 <strong>of</strong> 

389 649) without antibiotics, and increased with age. <strong>Antibiotics</strong> halved the risk <strong>of</strong> 

mastoiditis. General practitioners would need to treat 4831 otitis media episodes with 

antibiotics to prevent 1 child from developing mastoiditis. If antibiotics were no 

longer prescribed <strong>for</strong> otitis media, an extra 255 cases <strong>of</strong> childhood mastoiditis would 

occur, but there would be 738 775 fewer antibiotic prescriptions per year in the 

United Kingdom. 

CONCLUSIONS. Most children with mastoiditis have not seen their general practitioner 

<strong>for</strong> otitis media. <strong>Antibiotics</strong> halve the risk <strong>of</strong> mastoiditis, but the high number <strong>of</strong> 

episodes needing treatment to prevent 1 case precludes the treatment <strong>of</strong> otitis media 

as a strategy <strong>for</strong> preventing mastoiditis. Although mastoiditis is a serious disease, 

most children make an uncomplicated recovery after mastoidectomy or intravenous 

antibiotics. Treating these additional otitis media episodes could pose a larger public 

health problem in terms <strong>of</strong> antibiotic resistance. Pediatrics 2009;123:424–430 

Most children with mastoiditis have no recent history <strong>of</strong> otitis media. <strong>Antibiotics</strong> <strong>for</strong> otitis 

media halve the risk <strong>of</strong> mastoiditis, but the high NNT precludes the treatment <strong>of</strong> otitis 

media as a strategy <strong>for</strong> preventing mastoiditis. 

www.pediatrics.org/cgi/doi/10.1542/ 

peds.2007-3349 

doi:10.1542/peds.2007-3349 

Drs Sharland and Wong had the original 

idea <strong>for</strong> the study; Ms Thompson extracted 

the relevant data from the GPRD; Ms 

Thompson and Dr Gilbert developed the 

analytical strategy, and all authors were 

involved in the interpretation <strong>of</strong> the data; 

the manuscript was prepared by Ms 

Thompson in consultation with all other 

authors; and Dr Wong is the article 

guarantor. 

Key Words 

antibiotics, mastoiditis, otitis media, 

prescribing, pediatrics 

Abbreviations 

CI—confidence interval 

ENT—ear, nose, and throat 

GP—general practitioner 

GPRD—General Practice Research 

Database 

IQR—interquartile range 

NNT—number needed to treat 

OR—odds ratio 

Accepted <strong>for</strong> publication May 12, 2008 

Address correspondence to Ian Chi Kei Wong, 

BSc, MSc, PhD, University <strong>of</strong> London, Centre 

<strong>for</strong> Paediatric Pharmacy Research, School <strong>of</strong> 

Pharmacy, BMA House, Tavistock Square, 

London WC1H 9JP, England. E-mail: ian. 

wong@pharmacy.ac.uk 

PEDIATRICS (ISSN Numbers: Print, 0031-4005; 

Online, 1098-4275). Copyright © 2009 by the 

American Academy <strong>of</strong> Pediatrics 

OTITIS MEDIA IS among the most common infections <strong>of</strong> childhood, the main reason <strong>for</strong> a child to visit their 

primary care physician (ie, general practitioner [GP]) 1,2 and one <strong>of</strong> the primary childhood conditions <strong>for</strong> which 

GPs prescribe antibiotics. 3–5 <strong>Otitis</strong> media affects all age groups but is most frequent in the preschool years. 6 Most 

episodes are self-limiting without antibiotic treatment, 7 but otitis media is the major cause <strong>of</strong> childhood deafness8 and 

can lead to meningitis and mastoiditis, albeit rarely. 9 Marked variation in antibiotic prescribing between practices 

424 THOMPSON et al 



eflects the different thresholds GPs use when weighing 

the need to avoid unnecessary prescribing with the benefits 

<strong>of</strong> preventing complications such as mastoiditis. 10 

Recent findings from a meta-analysis <strong>of</strong> randomized, 

controlled trials involving 1643 children showed that 

children under 2 years <strong>of</strong> age stand to benefit most from 

antibiotics <strong>for</strong> otitis media. 11 The authors recommended 

observation rather than immediate antibiotic treatment 

<strong>for</strong> most children with acute otitis media, but this metaanalysis 

was not adequately powered to determine the 

protective effect <strong>of</strong> antibiotics <strong>for</strong> otitis media on the risk 

<strong>of</strong> mastoiditis. Findings from ecological analyses <strong>of</strong> routine 

health care databases have suggested that the reduction 

in GP prescribing <strong>of</strong> antibiotics to children may 

be associated with an increase in rare complications <strong>of</strong> 

bacterial infection, such as mastoiditis. One study associated 

the 23% decrease in overall antibiotic prescribing 

between 1996 and 2002 with an increase in hospital 

admissions <strong>for</strong> respiratory tract infections. 12 A data linkage 

study <strong>of</strong> 96 health authorities <strong>of</strong> England concluded 

that higher overall use <strong>of</strong> penicillin was associated with 

significantly fewer hospital admissions <strong>for</strong> mastoiditis. 13 

Another study noted that the 37% decline in overall 

antibiotic prescribing between 1993 and 2003 coincided 

with an increase in hospital admissions <strong>for</strong> mastoiditis in 

children under 4 years <strong>of</strong> age. 14 Large studies with treatment 

and outcome data on individual patients are now 

indicated to determine if these associations are explained 

by adverse effects <strong>of</strong> the decline in antibiotic use or 

changes in access to services, referral patterns, awareness 

<strong>of</strong> the diagnosis, and coding <strong>of</strong> routine data. 

In the United Kingdom, �98% <strong>of</strong> the population is 

registered with a National Health Service GP 15 and, on 

average, children (aged 0–15 years) consult their GP 

at least 3 times a year. 16,17 We used individual patient 

data from the UK General Practice Research Database 

(GPRD) to investigate whether the occurrence <strong>of</strong> mastoiditis 

is a useful marker <strong>of</strong> the potential adverse 

effects <strong>of</strong> reduced antibiotic prescribing. 

This study was conducted by the UK collaborative 

Improving Children’s Antibiotic Prescribing Group. 

PATIENTS AND METHODS 

Study Design 

We conducted a case review and retrospective cohort 

study by using the GPRD (Fig 1). All children aged 3 

months to 15 years who were registered with an “upto-standard” 

general practice (indicating that data recording 

by that practice has been verified to meet the 

required data quality criteria) 18 between January 1, 1990 

and December 31, 2006 were included. Children temporarily 

registered with a general practice were excluded 

to avoid duplication <strong>of</strong> data, because these children were 

most probably also permanently registered elsewhere. 

Source Data Set 

The GPRD is one <strong>of</strong> the world’s largest computerized 

databases <strong>of</strong> anonymized longitudinal general practice 

patient records, 19 comprising �6% <strong>of</strong> children in the UK 

census population. Practices contributing to the GPRD 

Total GPRD population: 3-mo- to 15-y-olds, 1990–2006 

7 119 677 child-years <strong>of</strong> data 

2 622 348 children 

Case review 

Incident mastoiditis: 

854 children 

Incident mastoiditis 

without otitis media 

within the preceding 

3 mo, or with 

comorbidity 

566 children 

FIGURE 1 

Schematic <strong>of</strong> mastoiditis case-review and cohort study. 

Cohort study 

<strong>Otitis</strong> media cohort 

(excluding children 

with comorbidity): 

1 182 272 episodes, 

464 845 children 

Incident mastoiditis: 

288 children 

are representative <strong>of</strong> practices in the total United Kingdom 

and are under contract to record all diagnoses, 

prescriptions, immunizations, hospital referrals, and test 

results <strong>of</strong> all active patients. Validation studies show 

quality and completeness <strong>of</strong> the GPRD data are high, 20 

and it has been used to investigate child health issues. 21,22 

Identification <strong>of</strong> Children With Mastoiditis and 

Exposures <strong>of</strong> Interest 

Diagnoses in the GPRD are classified by using either 

Ox<strong>for</strong>d Medical In<strong>for</strong>mation Systems or Read codes (see 

Tables 3 and 4, which are published as supporting 

in<strong>for</strong>mation on www.pediatrics.org/content/full/123/2/ 

424). We identified children with mastoiditis by searching 

the GPRD <strong>for</strong> codes relating to mastoiditis or mastoidectomy. 

Codes <strong>for</strong> mastoidectomy were used in 

addition to mastoiditis diagnosis codes to ensure that all 

children with mastoiditis were identified. We defined 

the date <strong>of</strong> diagnosis as the first record <strong>of</strong> mastoiditis and 

censored any subsequent episodes. To determine the 

prevalence <strong>of</strong> antecedent otitis media or comorbidities 

that might predispose to mastoiditis, we reviewed all GP 

attendances preceding the date <strong>of</strong> mastoiditis diagnosis 

and recorded any otitis media or related middle ear 

problems, antibiotic prescriptions, and immunologic, 

crani<strong>of</strong>acial, or neurologic abnormalities. Our use <strong>of</strong> a 

comprehensive approach to capture all diagnoses indicative 

<strong>of</strong> otitis media minimized the problems associated 

with variability in diagnostic coding between GPs. Any 

mention <strong>of</strong> otitis media within the same 14-day period 

was defined as 1 episode. All codes were identified from 

the GPRD medical/product dictionaries and validated by 

a pediatrician. Analyses <strong>of</strong> otitis media and antibiotic 

prescribing focused on events in the 3 months preceding 

mastoiditis, because mastoiditis is an acute complication 

<strong>of</strong> otitis media, 23–25 whereas analyses <strong>of</strong> predisposing fac- 

PEDIATRICS Volume 123, Number 2, February 2009 425 



tors such as immunologic, crani<strong>of</strong>acial, or neurologic 

abnormalities were based on the entire medical history 

preceding mastoiditis. 

Statistical Analyses 

Age- and calendar year-specific incidence rates <strong>for</strong> mastoiditis 

(with and without otitis media in the preceding 3 

months), <strong>for</strong> otitis media, and <strong>for</strong> antibiotic prescribing 

<strong>for</strong> otitis media were calculated per 1000 child-years at 

risk in the GPRD database. Ninety-five percent confidence 

intervals (CIs) were generated by using Poisson 

approximation, and tests <strong>for</strong> linear trend were conducted. 

Analyses <strong>of</strong> the effect <strong>of</strong> antibiotic treatment and 

other covariates on the risk <strong>of</strong> mastoiditis were confined 

to episodes <strong>of</strong> otitis media without immunologic, 

crani<strong>of</strong>acial, or neurologic abnormalities. We estimated 

the risk <strong>of</strong> mastoiditis in children within 3 

months <strong>of</strong> a treated and untreated otitis media episode. 

The negligible number <strong>of</strong> children (2.7%) with 

�3 months <strong>of</strong> follow-up time after an otitis media 

episode were included in these calculations. Children 

were classified as “treated” if they had an antibiotic 

prescribed in the same GP consultation as otitis media 

was diagnosed. If a child had multiple episodes <strong>of</strong> otitis 

media in the 3 months preceding mastoiditis, the episode 

closest to the date <strong>of</strong> mastoiditis was used. Because 

<strong>of</strong> potential miscoding <strong>of</strong> mastoiditis, we per<strong>for</strong>med 

sensitivity analyses <strong>of</strong> treatment efficacy 

restricted to children who had surgery <strong>for</strong> mastoiditis. 

We did not take into account clusters <strong>of</strong> repeated 

episodes <strong>of</strong> otitis media in the same child. The risk 

difference and number needed to treat (NNT) (1/risk 

difference) were computed. The effect <strong>of</strong> antibiotic 

treatment was determined by using logistic regression 

to calculate the crude odds ratios (OR) <strong>for</strong> mastoiditis 

<strong>for</strong> the following covariates: gender, age group, otitis 

media diagnosis, and number <strong>of</strong> otitis media episodes 

in the 3 months preceding mastoiditis. We retained 

covariates in the model that gave a P value <strong>of</strong> �.05 by 

using the likelihood ratio statistic. Data management 

and analysis were per<strong>for</strong>med by using Stata/SE 9.2 

s<strong>of</strong>tware (Stata Corp, College Station, TX). 26 

Ethics approval <strong>for</strong> this research was obtained from 

the Scientific and Ethical Advisory Group <strong>for</strong> the General 

Practice Research Database. 

RESULTS 

Between 1990 and 2006 there were 2 622 348 children 

aged 3 months to 15 years in the GPRD, contributing 

7 119 677 child-years <strong>of</strong> data (Fig 1) from 423 general 

practices; 854 children with mastoiditis were identified, 

all <strong>of</strong> which were incident cases. The median age at 

diagnosis was 9.7 years (interquartile range [IQR]: 6.2– 

12.9 years); incidence <strong>of</strong> mastoiditis peaked in children 

aged �1 year, with 10.3% (88 <strong>of</strong> 854) <strong>of</strong> all mastoiditis 

occurring in children �2 years old. Just more than half 

(57.6% [492 <strong>of</strong> 854]) were male. 

Only one third (35.7% [305 <strong>of</strong> 854]) <strong>of</strong> children with 

mastoiditis had visited their GP and been diagnosed with 


otitis media in the preceding 3 months. The average time 

between an episode <strong>of</strong> otitis media and mastoiditis was 

21.5 (IQR: 6.0–51.5) days. Almost half (47.5% [145 <strong>of</strong> 

305]) <strong>of</strong> the children with antecedent otitis media had 

been prescribed antibiotics <strong>for</strong> this condition, <strong>of</strong> whom 

76% received amoxicillin and 15% erythromycin. This is 

in accordance with the treatment recommendations <strong>for</strong> 

otitis media. 27 There were no differences in the choice <strong>of</strong> 

antibiotic therapy between children who developed 

mastoiditis after treated otitis media and those who did 

not. In total, 40.9% (349 <strong>of</strong> 854) <strong>of</strong> all children with 

mastoiditis had an antibiotic prescribed <strong>for</strong> any reason 

within the preceding 3 months; 53.6% (458 <strong>of</strong> 854) 

proceeded to mastoidectomy. Of the children with mastoiditis 

and antecedent otitis media, 5.6% (17 <strong>of</strong> 305) 

had an immunologic, crani<strong>of</strong>acial, or neurologic abnormality 

and were, there<strong>for</strong>e, excluded from the cohort 

analyses. 

We identified 1 182 272 episodes <strong>of</strong> otitis media in 

462 904 children. On average, children had 0.4 (SD: � 

0.80) episodes <strong>of</strong> otitis media per year, decreasing with 

increasing age. The median age at otitis media diagnosis 

was 5.4 (IQR: 2.3–7.7) years and approximately half 

(51.1% [604 113 <strong>of</strong> 1 182 272]) <strong>of</strong> the episodes occurred 

in boys. We found contrasting trends with age <strong>for</strong> rates 

<strong>of</strong> mastoiditis and otitis media diagnoses. The incidence 

<strong>of</strong> mastoiditis diagnoses was highest in infants, lowest in 

2-year-olds, and increased steadily with age thereafter. 

The increasing linear trend between 2 and 15 years <strong>of</strong> 

age was significant at the 5% level only <strong>for</strong> children 

without recognized antecedent otitis media (Fig 2). In 

contrast, the incidence <strong>of</strong> otitis media diagnoses decreased 

with increasing age (from 523.0 [95% CI: 520.7– 

525.3]) to 44.4 [95% CI: 43.8–45.0]) diagnoses per 

1000 child-years in 0- and 15-year-olds, respectively) 

(P � .01). 

The incidence <strong>of</strong> mastoiditis diagnoses remained stable 

between 1990 and 2006, with an average incidence 

<strong>of</strong> 0.12 (95% CI: 0.11–0.13) diagnoses per 1000 childyears. 

There was no evidence <strong>for</strong> a linear trend over time 

(P � .45) (Fig 3). In contrast, the incidence <strong>of</strong> otitis 

media diagnoses fell by 34% between 1990 and 2006 

from 221.4 (95% CI: 219.5–223.4) to 147.0 (95% CI: 

146.1–148.0) diagnoses per 1000 child-years (P � .01), 

whereas the incidence <strong>of</strong> antibiotic prescribing <strong>for</strong> otitis 

media declined by 49.6% from 170.4 (95% CI: 168.7– 

172.2) to 85.9 (95% CI: 85.2–86.7) prescriptions per 

1000 child-years (P � .01). The proportion <strong>of</strong> otitis media 

episodes treated with antibiotics decreased significantly 

over the study period, from 77% in 1990 to 58% 

in 2006 (P � .01). 

The prescription <strong>of</strong> antibiotics <strong>for</strong> otitis media significantly 

reduced the risk <strong>of</strong> developing mastoiditis 

within the following 3 months (OR: 0.56 [95% CI: 

0.44–0.71]; adjusted <strong>for</strong> gender, age group, and otitis 

media diagnosis) (Table 1). In sensitivity analyses restricted 

to children with mastoiditis requiring surgery, 

the adjusted OR was 0.39 (95% CI: 0.28–0.55; 55 

children in the treated group and 92 in the untreated 

group). The overall risk <strong>of</strong> developing mastoiditis 

within 3 months <strong>of</strong> an otitis media episode was 2.4 per 



Incidence <strong>of</strong> mastoiditis per 1000 child-years 

0.25 

0.20 

0.15 

0.10 

0.05 

0.00 

0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 

Age 

FIGURE 2 

Age-specific incidence <strong>of</strong> mastoiditis and otitis media diagnoses in UK general practices between 1990 and 2006. 

10 000 (288 <strong>of</strong> 1 182 272) otitis media episodes. 

Among children treated with antibiotics <strong>for</strong> otitis media, 

the risk <strong>of</strong> mastoiditis was 1.8 per 10 000 (139 <strong>of</strong> 

792 623) compared with 3.8 per 10 000 (149 <strong>of</strong> 

389 649) <strong>for</strong> untreated children (risk difference: 2.0 

per 10 000 otitis media episodes) (Table 2). The likelihood 

<strong>of</strong> a child receiving an antibiotic <strong>for</strong> otitis media 

was significantly associated with age (P � .01), with 

older children being less likely to receive a prescription. 

On average, 4831 episodes <strong>of</strong> otitis media would need 

to be treated with antibiotics to prevent 1 child from 

Incidence <strong>of</strong> mastoiditis per 1000 child-years 

0.25 

0.20 

0.15 

0.10 

0.05 

0.00 

Mastoiditis with otitis media 

Mastoiditis without recognized otitis media 

<strong>Otitis</strong> media 

developing mastoiditis (Table 2). The NNT was lower in 

older age groups but still exceeded 2000. Based on data 

extracted from the GPRD <strong>for</strong> the year 2006, there were 

�1 273 750 episodes <strong>of</strong> otitis media per year in children 

in the United Kingdom, <strong>of</strong> which 58% received an antibiotic. 

Completely stopping the practice <strong>of</strong> prescribing 

antibiotics <strong>for</strong> otitis media would result in an additional 

2 cases <strong>of</strong> mastoiditis per 10 000 otitis media episodes 

(risk difference). This would total 255 extra cases <strong>of</strong> 

childhood mastoiditis per year in the United Kingdom 

while reducing antibiotic usage by 738 775 prescriptions 

per year. 

1990 1991 1992 1993 1994 1995 1996 1997 1998 1999 2000 2001 2002 2003 2004 2005 2006 

Year 

Mastoiditis 

Antibiotic prescribing <strong>for</strong> otitis media 

FIGURE 3 

Annual incidence <strong>of</strong> mastoiditis diagnoses and antibiotic prescribing <strong>for</strong> otitis media in children 3 months to 15 years <strong>of</strong> age in UK general practices. 



www.pediatrics.org at Universitaet Zuerich on March 13, 2009 

80 

60 

40 

20 

0 

600 

500 

400 

300 

200 

100 

0 

200 

180 

160 

140 

120 

100 

Incidence <strong>of</strong> otitis media per 1000 child-years 

Incidence <strong>of</strong> antibiotic prescribing <strong>for</strong> otitis media 

per 1000 child-years

TABLE 1 Risk <strong>of</strong> Mastoiditis After <strong>Otitis</strong> <strong>Media</strong>: Variation Across Covariates 

Covariate OM Episodes 

(N � 1 182 272), n 

DISCUSSION 

Summary <strong>of</strong> Main Findings 

Mastoiditis is a rare condition, affecting 1.2 children per 

10 000 years <strong>of</strong> follow-up. Only one third <strong>of</strong> affected 

children had a GP record <strong>for</strong> otitis media within the 

preceding 3 months. The risk <strong>of</strong> mastoiditis after an otitis 

media episode increased with age but was never �16 per 

10 000 otitis media episodes. Antibiotic prescribing <strong>for</strong> 

otitis media decreased by 50% over the study period, but 

the rate <strong>of</strong> mastoiditis diagnoses remained relatively stable. 

<strong>Antibiotics</strong> halved the risk <strong>of</strong> mastoiditis in children 

with otitis media but, because <strong>of</strong> the low risk <strong>of</strong> mastoiditis, 

the number <strong>of</strong> otitis media episodes needing 

antibiotic treatment to prevent 1 case <strong>of</strong> mastoiditis 

(NNT) is very high. 

Methodology Issues 

The strengths <strong>of</strong> this study were the large sample size, 

which allows <strong>for</strong> examination <strong>of</strong> the risk <strong>of</strong> mastoiditis 

according to patient characteristic and antibiotic treat- 



(N � 288), n 

Crude OR 

(95% CI) 

Adjusted OR a 

(95% CI) 

Antibiotic treatment 

Treated 792 623 139 0.46 (0.36–0.58) 0.56 (0.44–0.71) 

Untreated 

Gender 

389 649 149 — — 

Male 604 113 161 1.21 (0.96–1.53) 1.35 (1.07–1.71) 

Female 

Age group, y 

578 159 127 — — 

�2 260 139 34 0.19 (0.13–0.28) 0.21 (0.14–0.30) 

2–5 494 522 52 0.15 (0.11–0.21) 0.16 (0.11–0.23) 

6–10 292 344 108 0.53 (0.40–0.70) 0.54 (0.41–0.71) 

11–15 

OM diagnosis 

135 267 94 — — 

Acute OM 260 912 36 0.50 (0.36–0.72) 0.65 (0.45–0.93) 

Other OM 

OM episodes in 3 mo preceding 

mastoiditis 

921 324 252 — — 

�1 981 878 41 0.81 (0.58–1.13) — 

1 

OM indicates otitis media. 

200 394 247 — — 

a Adjusted <strong>for</strong> antibiotic treatment, gender, age-group, and OM diagnosis. 

ment, and the representiveness <strong>of</strong> practices in the UK 

primary care setting. 

The major weakness, common to all studies based on 

routinely collected clinical data, was misclassification <strong>of</strong> 

the occurrence and timing <strong>of</strong> exposures. The incidence 

<strong>of</strong> mastoiditis may have been under-estimated as it is 

possible that not all hospital diagnoses <strong>of</strong> mastoiditis 

were entered into the GPRD. However, over-estimation 

is unlikely to be a problem as mastoiditis is an unusual 

and specific condition. Mastoiditis may have been miscoded, 

but restriction <strong>of</strong> analyses to mastoiditis requiring 

surgery did not significantly change the treatment effect. 

Under-reporting <strong>of</strong> otitis media could have occurred if 

GPs recorded episodes under other categories, such as 

upper respiratory tract infection. Finally, treatment efficacy 

could have been underestimated if GPs were more 

likely to record otitis media if they prescribed antibiotics 

than when no antibiotics were prescribed. 

A limitation <strong>of</strong> the GPRD is that prescriptions are not 

directly linked to indication. Our linkage method as- 

TABLE 2 Number <strong>of</strong> <strong>Otitis</strong> <strong>Media</strong> Episodes Needing Antibiotic Treatment to Prevent 1 Child From 

Developing Mastoiditis Stratified According to Age Group 

Age Group, 

y 

Antibiotic 

Treatment 

OM Episodes 

(n � 1 182 272) 


(n � 288) 

Risk <strong>of</strong> Mastoiditis/ 

10 000 OM 

Risk Difference 

(95% CI) 

�2 Treated 191 728 20 1.0 1.0 (0.2–2.2) 9970 

Untreated 68 411 14 2.0 — — 

2–5 Treated 338 939 29 0.9 0.6 (0.06–1.3) 16 051 

Untreated 155 583 23 1.5 — — 

6–10 Treated 181 042 49 2.7 2.6 (1.0–4.1) 3855 

Untreated 111 302 59 5.3 — — 

11–15 Treated 80 914 41 5.1 4.7 (1.6–7.7) 2135 

Untreated 54 353 53 9.8 — — 

Total Treated 792 623 139 1.8 2.0 (1.4–2.8) 4831 

Untreated 389 649 149 3.8 — — 


www.pediatrics.org at Universitaet Zuerich on March 13, 2009 

NNT

sumed that antibiotics prescribed in the same GP consultation 

as otitis media was diagnosed were <strong>for</strong> the 

treatment <strong>of</strong> otitis media. However, this assumption 

should not have influenced the mastoiditis outcome 

analysis so long as the antibiotic would be appropriate 

<strong>for</strong> the treatment <strong>of</strong> otitis media. Compliance data are 

not available in the GPRD, thus, the treated group may 

have included patients who did not fill or take their 

antibiotic prescription. Lack <strong>of</strong> severity data meant that 

we could not examine whether children with severe 

otitis media were more likely to be treated with an 

antibiotic and were at greater risk <strong>of</strong> developing mastoiditis. 

Both poor compliance and indication bias would 

bias treatment efficacy toward the null effect. 

Although the analyses did not account <strong>for</strong> clusters <strong>of</strong> 

repeated otitis media episodes in children, we found no 

effect <strong>of</strong> the number <strong>of</strong> otitis media episodes within the 

3 months preceding mastoiditis (P � .05). Inclusion in 

the analyses <strong>of</strong> treatment efficacy <strong>of</strong> the small number <strong>of</strong> 

otitis media episodes with �3 months <strong>of</strong> follow-up is 

unlikely to have biased results as loss to follow-up was 

unlikely to have been conditional on whether mastoiditis 

developed or not. 

Mastoiditis is not a useful marker <strong>of</strong> the potential 

adverse effects <strong>of</strong> reduced antibiotic prescribing. Firstly, 

it is a nonspecific marker as only a small proportion (one 

third) <strong>of</strong> mastoiditis cases are affected by changes in 

antibiotic prescribing practice <strong>for</strong> otitis media. Secondly, 

it is insensitive as mastoiditis is a rare disease. 

Strengths and Weaknesses in Relation to Other Studies 

This is the largest study to investigate the frequency <strong>of</strong> 

antecedent otitis media in children with mastoiditis and 

the first study to investigate the potential adverse effects 

<strong>of</strong> reduced antibiotic prescribing <strong>for</strong> otitis media on mastoiditis, 

specifically in children. The national representiveness 

<strong>of</strong> our study is confirmed by the consistency <strong>of</strong> 

findings from other UK-wide studies with our results. 

The UK incidence <strong>of</strong> mastoiditis in 0- to 14-year-olds 

between 1991 and 1998 was reported as 0.15 per 1000 

child-years (Department <strong>of</strong> Health hospital discharge data), 

28 which is comparable with our finding <strong>of</strong> 0.12 per 

1000 child-years in 3 months to 15-year-olds. The occurrence 

<strong>of</strong> mastoiditis without preceding otitis media 

has also been observed in other case-review studies, 29–31 

with approximately half <strong>of</strong> all affected children having 

no recent history <strong>of</strong> otitis media. 

The age distribution <strong>of</strong> our study does differ in comparison 

to existing literature, but previous research has 

been based on case-series, which could be biased by 

referral practice. For example, most studies cite the rate 

<strong>of</strong> mastoiditis as peaking among 1- to 4-year-olds, but 

these analyses are mainly based on patients presenting 

to children’s ear, nose, and throat (ENT) specialists and 

may ignore mastoiditis in adolescents, who could be 

referred to adult ENT specialists. 

A recent study used the GPRD to investigate the 

extent to which antibiotics reduce the risk <strong>of</strong> serious 

complications after common respiratory tract infections, 

including mastoiditis after otitis media. 32 The study 

found that antibiotics halved the risk <strong>of</strong> mastoiditis (ad- 

justed OR: 0.56 [95% CI: 0.37–0.86]), estimating that 

4064 episodes <strong>of</strong> otitis media would need to be treated 

with antibiotics to prevent 1 case <strong>of</strong> mastoiditis, which is 

in agreement with our findings. However, our study 

provides additional analyses, examining the antecedents 

<strong>of</strong> mastoiditis and the effect <strong>of</strong> age and changes in antibiotic 

prescribing on mastoiditis over time, specifically in 

children. Our data set comprised over twice as many 

general practices, yielding more than double the number 

<strong>of</strong> otitis media episodes <strong>for</strong> follow-up. Our study period 

also included more up-to-date in<strong>for</strong>mation. 

CONCLUSIONS 

Most children with mastoiditis have not previously seen 

their GP <strong>for</strong> otitis media. The use <strong>of</strong> antibiotics <strong>for</strong> otitis 

media halves the risk <strong>of</strong> mastoiditis, but the high number 

needing treatment to prevent 1 case precludes the 

treatment <strong>of</strong> otitis media as a strategy to prevent mastoiditis. 

Even in adolescents with otitis media, who are 

most at risk <strong>of</strong> developing mastoiditis, the NNT exceeds 

2000. Although mastoiditis is a serious disease, most 

children make an uncomplicated recovery after mastoidectomy 

or intravenous antibiotics. Treating these additional 

otitis media episodes could pose a larger public 

health problem because <strong>of</strong> the possibility <strong>of</strong> future treatment 

failure as a result <strong>of</strong> antibiotic-resistant pathogens, 

increased exposure <strong>of</strong> children to the adverse reactions 

to antibiotic treatment, and unnecessary prescribing 

costs. Nevertheless, GPs and pediatricians working in 

primary care need to be able to recognize the signs <strong>of</strong> 

mastoiditis (postauricular swelling and protrusion <strong>of</strong> the 

auricle), 31 particularly in older children, and to refer 

promptly to ENT services. 

Recent data suggest that the pneumococcal conjugate 

vaccine Prevenar (introduced into the UK immunization 

schedule from September 2006) 33 is effective in reducing 

otitis media-related consultations and antibiotic prescribing 

<strong>for</strong> such. 34 This may result in a future decline in 

mastoiditis. Trends in antibiotic prescribing need to be 

<strong>for</strong>mally monitored in association with the longitudinal 

follow-up <strong>of</strong> individual patient disease outcomes data, to 

ensure that any changes in antibiotic use are not causing 

harm. 

ACKNOWLEDGMENTS 

Dr Wong’s post was funded by a Department <strong>of</strong> Health 

Public Health Career Scientist Award. Dr Saxena was 

funded by a postdoctoral award from the Department <strong>of</strong> 

Health. The license <strong>for</strong> the GPRD was funded by the 

European Commission via the Task<strong>for</strong>ce European Drug 

Development <strong>for</strong> the Young (TEDDY) network <strong>of</strong> Excellence 

European Commission Framework 6 Programme, 

2005–2010. 

We thank the general practitioners who contributed 

data to the GPRD. 

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<strong>Effect</strong> <strong>of</strong> <strong>Antibiotics</strong> <strong>for</strong> <strong>Otitis</strong> <strong>Media</strong> on Mastoiditis in Children: A Retrospective 

Cohort Study Using the United Kingdom General Practice Research Database 

Paula Louise Thompson, Ruth E. Gilbert, Paul F. Long, Sonia Saxena, Mike Sharland 

and Ian Chi Kei Wong 

Pediatrics 2009;123;424-430 

DOI: 10.1542/peds.2007-3349 

Updated In<strong>for</strong>mation 

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