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
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Abstract |
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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.
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; 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
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Introduction |
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Antimicrobial resistance among Streptococcus pneumoniae is rapidly increasing in several countries,46 and the single most important 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.
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Materials and methods |
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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.
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 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
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Results |
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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.
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The most frequently used antibiotics were cephalosporins (43.7% of treated children), followed by macrolides, a combination of penicillins plus ß-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).
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There were 19 364 prescriptions for topical antibiotics for eye infections, in 16 198 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 non-associated 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%).
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Discussion |
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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 prescriptions/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.
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 ß-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, ß-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 strains. The effectiveness of any intervention could be monitored by repeating this survey.
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Acknowledgements |
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Footnotes |
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Members of the Emilia Romagna Study Group on the Use of Antibiotics in Children are listed in the Acknowledgements.
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References |
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