Journal of Antimicrobial Chemotherapy (2003) 52, 282286

DOI: 10.1093/jac/dkg302
Advance Access publication 15 July 2003

Antibiotic prescriptions in children

D. Resi*, M. Milandri, M. L. Moro and the Emilia Romagna Study Group on the Use of Antibiotics in
Children
Agenzia Sanitaria Regionale Emilia Romagna, Area Rischio Infettivo, Viale Aldo Moro 21, 40127 Bologna, Italy
Received 20 December 2002; returned 27 February 2003; revised 17 April 2003; accepted 25 April 2003

Objectives: The aim of this study was to evaluate antibiotic prescription for children in Emilia Romagna, a
Northern Italian region with 414 880 people aged 114 years.

Results: In the year surveyed, 511270 antibiotic prescriptions in 219 257 children were identified. In all,
52.9% of children received at least one antibiotic; this percentage decreased with age, ranging from 70.4% in
children 12 years old to 35.8% in children >11 years old. Fifty-two per cent of inhabitants under the age of
15 years were treated with systemic antibiotics at least once in the year. Cephalosporins were mostly
prescribed in the youngest children, while macrolides were most frequently used in children over 6 years
old. In all 3.9% of children were treated with topical antibiotics.
Conclusions: This study has shown that paediatric antibiotic prescription rates can be derived from analysis
of regional drug and resident databases. High antibiotic usage is shown in the paediatric population of
Emilia Romagna, similar to that observed in other regions of Northern Italy. Broad-spectrum antibiotics are
predominantly prescribed. Comparison with prescription rates from other countries paediatric populations
suggests there is extensive antibiotic overuse in Italy. This could be associated with selection for and
dissemination of antibiotic resistance. Interventions are needed to reduce consumption.
Keywords: pharmacoepidemiology, paediatricians prescriptions, drug utilization

Introduction
In the USA almost three-quarters of all outpatient antibiotics are
prescribed for acute respiratory infections.1 A significant proportion
of antibiotics prescribed every year in the community are given to
children and 50% of prescriptions for children given by general
practitioners are unnecessary. In the USA 44% of children with
common colds were reported to be treated with antibiotics, 46%
of those with upper respiratory infections, and 75% of those with
bronchitis, conditions that typically do not benefit from antibiotic
treatment.2 In Canada, 74% of preschool children seeking care for
respiratory infections received antibiotic prescriptions; in 85% of
these cases such prescriptions were inappropriate.3
Antimicrobial resistance among Streptococcus pneumoniae is
rapidly increasing in several countries,46 and the single most import-

ant factor in the emergence of antibiotic resistance among respiratory

bacterial pathogens is selection pressure from antimicrobial agents.7
Observational8 and intervention9 studies from several countries have
supported a link between rates of antibiotic prescription and resistance in communities. Thus, reduction of inappropriate use of antibiotics in the community should be considered a major public health
issue.
Existing reports of population-based antibiotic use in children are
relatively few. This paper describes the pattern of individual prescriptions of systemic and topical antibiotics used for eye infections
in children and adolescents <15 years old in Emilia Romagna (Northern Italy) in the year 2000, reported to the Regional Health Service
data system.

..................................................................................................................................................................................................................................................................

*Corresponding author. Tel: +39-051-6397134; Fax: +39-051-6397053; E-mail: dresi@asr.regione.emilia-romagna.it

Members of the Emilia Romagna Study Group on the Use of Antibiotics in Children are listed in the Acknowledgements.
...................................................................................................................................................................................................................................................................

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Methods: The regional Prescription Database of drugs reimbursed by the Italian National Health Service
was used in this study. Antibiotic use was estimated as the proportion of children who received at least one
prescription during the year 2000 (number of children treated per 100 inhabitants per year). To evaluate the
frequency of exposure for each child, all the prescriptions given within a period shorter than 12 days were
considered as a single treatment.

Antibiotic prescriptions in children

Table 1. Paediatric population, treated children and number of treated children per 100 inhabitants by age
groups and by sex

Paediatric population
Age group (years)
12
36
710
1114
Total

Treated children/
100 inhabitants/year

Treated children

total

total

total

31.029
60.219
60.256
49.785
201.289

33.168
63.893
63.814
52.716
213.591

64.197
124.112
124.070
102.501
414.880

21.511
38.445
27.886
17.473
105.315

23.710
41.570
29.431
19.231
113.942

45.221
80.015
57.317
36.704
219.257

69.3
63.8
46.3
35.1
52.3

71.5
65.1
46.1
36.5
53.3

70.4
64.5
46.2
35.8
52.9

F, female; M, male.

Materials and methods

Setting

Analysis
To identify antibiotic prescriptions, the regional database of drug
prescriptions was used; the file includes all the prescriptions for drugs
reimbursed by the Italian National Health Service. The file was linked to
the regional database of the resident population to identify prescriptions
of antibiotics provided to children 114 years old in Emilia Romagna,
from 1 January to 31 December 2000.
Information contained in the files and considered for the analysis were
patients age and gender, dispensed product according to the Anatomical
Therapeutic Chemical classification and date of prescription. All prescriptions for systemic antibiotics (J01) and topical antibiotics used in
eye infections (S01AA, S01AX, S01CA) were identified.
Childrens ages were calculated at a middle date of the year, 1 July
2000.
The amount of antibiotic use was estimated using the following
parameters: (i) the proportion of children who received at least one prescription during 2000 (number of treated children per 100 inhabitants per
year); (ii) the proportion of children in the population who underwent
0, 1, 2 or 3 antibiotic treatments during 2000; all the prescriptions given
to a single child within a time period shorter than or equal to 11 days
(number of days from the first prescription to the following one) were
considered as one treatment.10
Distribution of prescriptions by antibiotic therapeutic category and
by antibiotic molecule were analysed. For each category and type of

Results
In the year surveyed, 511 270 antibiotic prescriptions in 219 257
children were identified. In all 52.9% of children received at least
one antibiotic prescription; this percentage decreased with age, from
70.4% in children 12 years old to 35.8% in children >11 years old
(Table 1). The frequency of systemic and topical antibiotics prescriptions did not vary by gender.

Systemic antibiotics
The database included 491 906 prescriptions of systemic antibiotics
in 215 696 children; the mean prescription rate was 119 prescriptions/
100 children/year. Fifty-two per cent of inhabitants <15 years old
were treated with systemic antibiotic at least once in the year.
Table 2 shows that antibiotic use is greater in children <6 years
old; two-thirds of children in this age group received one or more
prescriptions. A high proportion of children received more than one
antibiotic course during the study period. Figure 1 shows that the
number of treatments varies by age group: the proportion of children
who received two or more treatments decreased significantly after 2
years of age.
The most common route of administration for systemic antibiotics
was oral, while only a small proportion of children received a
parenteral antibiotic (5% of treated children). This percentage
decreased from 6.2% in the 12 years age group to <4% in the >6
years age group.
The most frequently used antibiotics were cephalosporins (43.7%
of treated children), followed by macrolides, a combination of penicillins plus -lactamase inhibitors, and broad-spectrum penicillins
(40.1%, 29.8% and 29.4%, respectively). Cephalosporins were frequently prescribed in the youngest children and macrolides were
mostly prescribed in children >6 years of age (Figure 2).
Table 3 shows that the combination of amoxicillin plus clavulanic
acid and amoxicillin were the most frequently prescribed in the
whole population. In the 12 years age group, amoxicillin was the
most frequently prescribed antibiotic, while in older children the
combination of amoxicillin and -lactamase inhibitor was preferred.
Cefaclor, a second-generation cephalosporin, was the third most fre-

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Emilia Romagna is one of the 20 Italian regions and it is located in the

north of the country. On 1 January 2000, the population of Emilia
Romagna was nearly 4 million inhabitants, including 414 880 children 114
years old, accounting for 5.3% of the entire Italian paediatric population
in this age group. Children <1 year of age were not included in this
analysis because length of exposure to antibiotics in this age class varied
according to actual date of birth, while in all other age classes we could
observe exposure for a whole year. Inclusion of children <1 year of age
would have required that analysis be carried out by person-years of
exposure.
The Italian health care system is organized uniformly; people are
registered by their individual practitioner and receive free medical care.
The National Health Service ensures free access to hospitals and reimburses
100% of the cost of oral antibiotics prescribed, independently of social
status and income, and 100% of injectable antibiotics when considered
appropriate. Pharmacies send prescription data to the regional database
through a computerized accounting system.

antibiotic, the proportion of children who used at least once the specific
antibiotic among children who received at least one prescription was
calculated. Antimycotics were not included in this study.
Data were analysed using SAS software.11

D. Resi et al.
Table 2. Number of children treated with systemic and topical antibiotics per 100 inhabitants by age
group
Systemic antibiotics

Age group (years)

12
36
710
1114
Total

Topical antibiotics

treated children

treated children/100
inhabitants/year

treated children

treated children/100
inhabitants/year

44.464
78.956
56.318
35.958
215.696

69.3
63.6
45.4
35.1
52.0

5.508
6.279
2.775
1.636
16.198

8.6
5.1
2.2
1.6
3.9

quently prescribed antibiotic in the 12 and 36 years age groups; in

the other age groups macrolides such as clarithromycin were the third
most frequently prescribed drugs.

Topical antibiotics
There were 19364 prescriptions for topical antibiotics for eye infections, in 16198 children corresponding to 3.9% of children treated
with these antibiotics. The prescription rate was higher for 12 years
age group (8.6%) and gradually decreased with age to 1.6% in the
oldest age class. The mean prescription rate was 5 prescriptions/100
children/year.
Overall, the most frequently prescribed groups (72.7%) were nonassociated antibiotics (S01AA and S01AX). S01CA (combination of
antibiotics and corticosteroids) were the most used topical antibiotics
in the 710 and 1114 years groups (43.7% and 55%).

Discussion
Existing reports of antibiotics are usually based on wholesale statistics or studies of small populations, and few population-based reports
on antibiotic prescriptions in paediatric populations have been published. As far as we know, the only paper reporting population-based
data, while taking into account multiple antibiotic prescriptions to an
individual child, is the paper by Thrane et al.,12 who report antibiotic
data from a Danish county in 1997.
In comparison to data reported by Thrane et al.12 in the North
Jutland county, the amount of antibiotic use in the paediatric population of Emilia Romagna is significantly higher, in terms of both the
number of children receiving at least one prescription in a year and
the number of antibiotic treatments per year. In Denmark, 429 pre-

Figure 2. Most frequently prescribed therapeutic groups of antibiotics by age

(percentage of total treatments).

scriptions/1000 children/year were recorded, compared with 1190

prescriptions/1000 children/year in the present study (+177.4%); the
proportion of children receiving at least one antibiotic prescription
per year was 29% in Denmark compared with 52% in Emilia
Romagna (+79.3%), with significant differences between age
classes: in Emilia Romagna, the proportion of treated children was
39.4% higher among 12 year olds (49.7% in Denmark versus
69.3% in Emilia Romagna), but this proportion was 105.3% higher
among 1115 year olds (17.1% in Denmark versus 35.1% in Emilia
Romagna). Moreover, in Emilia Romagna, three or more treatments
were prescribed to 25.1% of the toddlers (12 years age group), to
7.1% of the 710 years group and to 3.7% of children >10 years
old, compared with 12% of toddlers and 1% of children >7 years in
Denmark. Independent of the overall use of antibiotics in Emilia
Romagna and Denmark, antibiotic prescription in children was in
both cases higher in the first years of life.12 In our opinion, differences
in population density (178 versus 80 inhabitants/km2 for Emilia
Romagna and North Jutland, respectively) between the two countries
are not sufficient to explain variation in antibiotic consumption.

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Figure 1. Proportion of children with 1, 2 or 3 treatments with systemic antibiotics by age group (years).

Antibiotic prescriptions in children

Table 3. Most prescribed molecules of antibiotics by age classes (percentage of treated
children)
Age group (years)
ATC

12

36

710

1114

total

amoxicillin and -lactamase inhibitor

amoxicillin
clarithromycin
cefaclor
azithromycin
cefixime
ceftibuten
rokitamycin
cefprozil
cefuroxime
ceftriaxone
cefpodoxime
roxithromycin
trimethoprim/sulphonamide
erythromycin

28.6
39.8
16.7
25.7
14.0
16.8
12.5
6.8
7.6
5.2
4.6
2.5
0.9
1.5
1.1

32.3
28.3
19.1
20.6
16.6
16.0
9.5
8.2
7.1
6.4
3.6
2.6
1.3
1.5
1.2

28.7
25.0
18.5
9.3
16.4
10.0
4.5
6.7
3.5
5.3
2.3
2.4
2.5
1.9
1.6

27.6
23.8
17.5
3.6
16.2
6.7
2.9
4.6
2.7
4.3
2.0
1.8
4.4
2.5
1.6

27.3
26.7
16.7
14.6
14.6
11.9
7.1
6.3
5.1
5.0
2.9
2.2
1.9
1.6
1.2

ATC, Anatomical Therapeutic Chemical.

The observed differences in antibiotic prescription behaviour

between Denmark and Italy are confirmed by the results of a recent
study that compared antibiotic prescription pattern in the Ravenna
Local Health Authority, one of the 13 Emilia Romagna Health
Authorities, and the county of Funen (Denmark).13 These data
showed significantly higher antibiotic prescribing in Ravenna, in all
age groups, in terms of both prevalence of use and overall antibiotic
prescription expressed as defined daily dosage (DDD) per inhabitant.
Moreover, while in Funen the age group with the maximal antibiotic
consumption was the elderly population (>80 years), with 20.1 DDD/
1000 inhabitants day, in Ravenna the age group 09 years scored
highest, with 23.6 DDD/1000 inhabitants day.
The striking differences observed between Emilia Romagna
and Denmark are due to the fact that Denmark, according to a recent
survey, is one of the European countries consuming less outpatient
antibiotics, while Italy ranked sixth after France, Spain, Portugal,
Belgium and Luxembourg, the countries with the highest sales.14
The antibiotic usage in the paediatric population reported in
Emilia Romagna is similar to that observed in other Northern Italian
regions: the prevalence of usage among children was 55.2% in 1999
in a study involving three northern regions15 and 42% in 1997 in
another study.16 Antibiotic pressure on children is probably even
higher in the south, given the large variations among Italian regions,
according to Italian National Statistics on drug use published by the
Italian Ministry of Health:17 the overall consumption of antibiotics in
Italy in year 2000 was 22.7 DDD/1000 inhabitants, ranging from
17.7/1000 in the north to 29.8/1000 in the south.
A limitation of the present study is that it is based on reimbursement data, and this could have caused an underestimate of real
exposure to antibiotics, due to antibiotics prescribed by private
physicians or antibiotics obtained over the counter.
A recent study involving 42 community paediatricians in Southern Italy showed that 22% of the expenditure for antibacterials was
sustained directly by the family, reaching 60% for cheaper antibiotics
such as amoxicillin.18 Thus, antibiotic exposure can actually be
significantly higher than that described by reimbursement data.

Another limitation of our study is that reimbursement data do not

provide information about the indications for the prescription of
these drugs; as a consequence, no information is available regarding
reasons for and appropriateness of prescribing.
The strengths of the study are the large population size, and reproducible analysis and results.
The selection of antibiotics by Emilia Romagna physicians in the
paediatric population is significantly different from that reported in
Denmark:12 Italian children received significantly more cephalosporins, broad-spectrum penicillins, including combinations with
-lactamase inhibitors, and macrolides than Danish children. In
Denmark there is no reimbursement for oral cephalosporins in the
community and this alone may explain the difference. Other factors
may contribute to this differences, such as industry pressure and
existing policies on the use of antimicrobials in respiratory infections. In Emilia Romagna, penicillin V was even not included among
the 15 most frequently prescribed drugs.
This study raises considerable concern about the possible effects
on antimicrobial resistance of the observed high selective antibiotic
pressure in the paediatric population.1921 Resistance surveillance
data available in Italy show that macrolide resistance in Streptococcus pyogenes and Streptococcus pneumoniae is >30%; penicillin
non-susceptible S. pneumoniae strains in invasive diseases are still
not as widely spread as in Spain or France, but their frequency is
increasing.2225 Moreover, -lactamase production is increasing in
Haemophilus influenzae, and is nowadays present in >80% of the
Moraxella spp. strains.26
In conclusion, we have used linkage of reimbursement and
population databases to estimate antibiotic prescription rates for
children in an Italian region. Comparison of these rates with those for
Denmark reveals a large difference, with Italian children receiving
more courses of antibiotics and broader spectrum agents.
We would encourage interventions aimed at reducing overuse and
improving quality of care in the paediatric population, in order to prevent further selection for and dissemination of antibiotic resistant

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J01CR02
J01CA04
J01FA09
J01DA08
J01FA10
J01DA23
J01DA39
J01FA12
J01DA41
J01DA06
J01DA13
J01DA33
J01FA06
J01EE01
J01FA01

Molecule

D. Resi et al.
strains. The effectiveness of any intervention could be monitored by
repeating this survey.

Acknowledgements
Members of the Emilia Romagna Study Group on the Use of Antibiotics in Children: Asciano Mara, Dalla Casa Paola, Martelli Luisa,
Morri Michela, Pascucci Maria Grazia, Polli Francesca, Reggiani
Lamberto, Sapigni Ester, Valenti Elisabetta and Venturi Iole.

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