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A population-based study of antibiotic prescriptions for Danish children

THRANE, NANA MD; STEFFENSEN, FLEMMING H. MD; MORTENSEN, JENS T. MD, PHD; SCHØNHEYDER, HENRIK C. DR MED SCI; SØRENSEN, HENRIK T. DRMEDSCI

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The Pediatric Infectious Disease Journal: April 1999 - Volume 18 - Issue 4 - p 333-337
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Abstract

INTRODUCTION

Infections are the most frequent diseases in the pediatric population. Children comprise 18% of the Danish population and account for ∼27% of the infections treated with antibiotics in general practice in Denmark. 1

Restrictive use of antibiotics is important from a public health point of view. The amount of antibiotics and the antiinfective spectrum are strong predictors for development and spread of antibiotic-resistant microorganisms.2, 3 Side effects are common and occur more often with use of broad spectrum than narrow spectrum antibiotics.4

The existing reports of antibiotic drug use are relatively few and usually based on wholesale statistics or studies of small populations.5-9 The population-based individual drug statistics gives the opportunity to estimate the proportion of drug users and the amount of drugs used by the individual.

On the basis of Danish Health Service data, we identified the individual prescriptions of systemic antibiotics and topical antibiotics used in eye infections for all the children age 0 to 15 years in North Jutland County, Denmark, written during 1997. Our specific aims were to examine, in relation to age and sex: (1) the amount of antibiotics used; (2) the proportion of children in the population receiving one or multiple prescriptions; and (3) the types of antibiotics prescribed.

METHODS

Setting. We used the population-based Pharmacoepidemiological Prescription Database of the County of North Jutland10 to identify all reimbursed prescriptions of antibiotics for children age 0 to 15 years from January 1, 1997, to December 31, 1997. On January 1, 1997, the population of the County of North Jutland was ∼492 000 inhabitants, including 95 134 children age 0 to 15 years. Denmark has an uniformly organized health care system, and the demographic and social differences between the 17 counties are small. Our database covers ∼10% of the whole population in Denmark. More than 98% of the Danish population are registered with their individual general practitioner and receive free medical care. The rest may consult a general practitioner of their choice but must pay part of the fee themselves. The pharmacies in the county use a computerized accounting system from which data are sent to the Danish National Health Service, which provides tax-supported health care for all the inhabitants of the county. The Health Service program ensures free access to hospitals and reimburses 50 to 75% of the cost of prescribed drugs, independently of social status and income.

The Pharmacoepidemiological Prescription Database. The information is transferred to the Prescription Database from the National Health Service. The data include the patient's personal identification number, the type of drug prescribed according to the anatomical therapeutic chemical (ATC) classification system and the date of purchase. The 10-digit personal identification number, which includes the date of birth, is given to all citizens shortly after birth and ensures that a complete prescription history can be established for all the inhabitants of the county. From April, 1996, the National Health Service implemented a new prescribing system for children, which is based on the child's personal identification number.

Antibiotics in Denmark are purchased on prescription only, but the database does not contain information about drugs not subsidized by the National Health Service, which is the case for cephalosporins and tetracyclines. For the general population tetracyclines comprised 8.2% and cephalosporins 0.2% of the total defined daily doses of antibiotics sold in the county in 1996.11 These estimates are based on wholesale statistics and are calculated independently of reimbursement. Tetracyclines are not recommended for children younger than 12 years.12

Analyses. We identified all recorded prescriptions for systemic antibiotics (ATC code J01) and topical antibiotics used in eye infections (ATC code S01AA, S01AB and S01AX).

The amount of antibiotic use was estimated as a prescription rate, i.e. number of prescriptions per 1000 children per year. The number of children refers to the population in the respective age groups. We aggregated the data on each child and calculated the number of prescriptions per child. Subsequently we estimated the proportion of children in the population who received 0, 1, 2 or ≥3 prescriptions. The confidence intervals (95% CI) were estimated with the PEPI program. The systemic antibiotics were classified into four groups: broad spectrum penicillins (ampicillin/pivampicillin/amoxicillin/amoxicillin with enzyme inhibitor/bacampicillin/amidopenicillin); narrow spectrum penicillins (penicillin V); macrolides; and miscellaneous, such as less frequently used drugs: sulfonamide-containing antiinfectives, other penicillins (dicloxacillin/methicillin/flucloxacillin), monobactams, quinolones and fusidic acid. Antimycotics were not included in this study. For each antibiotic group we calculated the proportion of the total number of antibiotic prescriptions. The topical antibiotics were classified into three groups: fusidic acid; chloramphenicol; and miscellaneous.

In the analyses of the aggregated data on each child, age was calculated at a fixed date, July 1, 1997, because all children, of course, change their age during a year. In the other analyses age refers to the child's age at the date of purchase of the prescription. The data were analyzed by the following age groups: <1 years (infants); 1 to 2 years (toddlers); 3 to 6 years (preschool children); 7 to 10 and 11 to 15 years (school children). These age groups comprised 7, 13, 27, 24 and 29%, respectively, of this child population.

RESULTS

The database comprised 157 704 prescriptions for all drugs for children, of which 59 155 were for antibiotics. Prescriptions for nonresidents of the county (1854 prescriptions) were excluded, leaving 57 301 prescriptions for the final analysis. Systemic antibiotics comprised 29% and topical antibiotics 8% of the total number of prescriptions. Almost two-thirds of the children <3 years (62.0%, 95% CI 61.3 to 62.6%) received at least one prescription for systemic and/or topical antibiotics.

Systemic antibiotics. We identified 44 640 prescriptions for systemic antibiotics, of which 52% were for boys and 48% for girls. The mean prescription rate was 429 prescriptions/1000 children/year. Figure 1 shows the prescription rates for the different age groups. The rate increased from infants to toddlers, and subsequently it gradually decreased.

Fig. 1
Fig. 1:
Prescription rate of systemic antibiotics, defined as the number of prescriptions/1000 children/year, by age groups in North Jutland County, Denmark, 1997.

Overall ∼29% (95% CI 28.5 to 29.1%) of the children in the population received at least one prescription. Figure 2 shows that systemic antibiotics were prescribed for one-half of the toddlers (49.7%, 95% CI 48.8 to 50.5%), one-third of the 3- to 6-year-olds (35.7%, 95% CI 35.1 to 36.3%) and one in six (17.1%, 95% CI: 16.7%-17.6%) of the 11-15 year-olds. Three or more prescriptions were purchased for ∼12% (95% CI 11.2 to 12,4%) of the toddlers and for ∼1% (95% CI 1.1 to 1.3%) of children older than 7 years. For infants, toddlers, preschool children and school children, children who reimbursed three or more prescriptions received 45, 48, 33 and 18%, respectively, of all the prescriptions in each age group.

Fig. 2
Fig. 2:
Proportion of children in the population with 0, 1, 2 or ≥3 prescriptions of systemic antibiotics, by age groups in North Jutland County, Denmark, 1997.

Overall 88% of prescriptions were penicillins and 10% were macrolides in all age groups. Figure 3 shows that the majority of prescriptions for children younger than 3 years were broad spectrum penicillins (57%). In children older than 6 years, penicillin V were the most frequently used antibiotics. The overall use of sulfonamide-containing antiinfectives was 2%.

Fig. 3
Fig. 3:
Distribution of antibiotic subgroups as percentage of total number of systemic antibiotic prescriptions, by age groups in North Jutland County, Denmark, 1997.

The routes of administration were oral (96%) and rectal (4%). However, in children younger than 3 years, 7% of the prescriptions were for rectal administration.

The 0- to 2-year-old children, who comprised 20% of the population, received 26% of the penicillin V prescribed, 55% of the broad spectrum penicillins and 38% of the macrolides.

Topical antibiotics. There were 12 661 prescriptions for topical antibiotics in 9966 children; 52% were for boys. The mean prescription rate was 133 prescriptions/1000 children/year. The rate was highest for toddlers, 436/1000 children/year, and it decreased continuously with age to ∼31/1000 children/year in the oldest age groups. One-third of the toddlers (31.6%, 95% CI 30.8 to 32.4%) received topical antibiotics. Prescriptions were purchased for ∼3% (95% CI 2.6 to 3.0%) of children older than 10 years. Two groups made up 99% of the prescriptions, fusidic acid 60% and chloramphenicol 39%.

DISCUSSION

Internationally Denmark is among the lowest users of antibiotics to humans with a defined daily dose level of ∼12 defined daily doses/1000 inhabitants/day.13, 14 However, we found that the majority of children younger than 3 years were treated with antibiotics during 1 year.

This study showed that Danish children received one-half as many systemic antibiotics as Swedish children ages 0 to 14 years did during 1993.5 The level of systemic antibiotic use in the United States in 1986 for children age 0 to 9 years was twice the level for Danish children in the same age in 1997.8 The variations according to age and sex were similar in the three countries.

Although the overall use might be low, we found a high use at the individual level, especially among young children. The literature concerning individual use is sparse,7, 15, 16 and we found no studies regarding multiple prescribing patterns. The two Swedish studies7, 15 were conducted more than 10 years ago. Because the antibiotic use in Swedish children has increased considerably during the past decade,5 there is not much point in making a comparison. Thus we do not know if the reason for the higher use in Sweden and the United States is that antibiotics are prescribed for more children or whether more courses of antibiotics are prescribed for the individual child.

Compared with those in other Scandinavian studies7, 9 Danish children received more broad spectrum penicillins but less macrolides and sulfonamide-containing antiinfectives. In the United States the vast majority of prescribed antibiotics in 1986 were broad spectrum in all age groups.8

In general the Danish guidelines recommend penicillin V as the drug of first choice in respiratory tract infections in all age groups.12, 17 Our finding that the majority of prescriptions for the youngest children were broad spectrum penicillins is therefore surprising. Because Danish children are vaccinated against Haemophilus influenzae type b, penicillin V is as effective as or may be more effective than ampicillins/amoxicillin for treatment of the most common pathogenic bacteria.12, 18, 19 Ampicillin/amoxicillin causes more side effects and induces bacterial resistance more often, and the cost of one treatment with penicillin V is about one-half the cost of ampicillin/amoxicillin.12 The sulfonamide-containing antiinfectives are used in Denmark only in urinary tract infections, and this is the reason for the low use.

The major strength of our study is the large size, the uniformly organized health care system allowing a population-based design and the completeness of the registrations, in contrast to primary data collection from studies based on general practitioners.1, 6 The weaknesses include: (1) the results may underestimate the real use because of implementation problems with the new prescribing system, and some patients purchase drugs while they are away from their home county; (2) inpatient use is not recorded in the database; and (3) information about indications for use are not available.

The association between recent use of oral antibiotics and drug resistance has been confirmed,2, 20, 21 so reducing inappropriate use of antimicrobials must be given priority. Compared with the rest of Europe, Asia, the Middle East and the United States, Denmark has a low level of antibiotic resistance, e.g. 1 to 2% of S. pneumoniae strains are resistant to penicillin,22, 23 and 4 to 21% of H. influenzae strains are resistant to ampicillin.23-25 Reports have documented, however, an increasing level of beta-lactamase-producing Branhamella catarrhalis26 and H. influenzae24 in Danish children.

We are not aware of any recent studies about the appropriateness of antibiotic prescriptions in Danish children. Studies from the United States and France have demonstrated that physicians as a matter of standard procedures prescribe antibiotics for clinical syndromes on which antibiotics have little or no effect.27, 28

Efforts are stressed to maintain or reduce the low antibiotic use in Denmark.29 We need guidelines on rational antibiotic prescribing that are based on efficacy evaluations of treatments and surveillance of antibiotic resistance patterns. Education of physicians and other medical staff is important. Increasing use of office-based diagnostic tests may lead to reduced prescribing of antibiotics, as a result of more accurate diagnoses.30 Prevention of infectious diseases may have an influence on antibiotic use, i.e. vaccination against S. pneumoniae and influenza virus. Furthermore we need continuous surveillance of antibiotic use in the population.

In summary the overall use of antibiotics in Danish children is low compared with that in other countries, but almost two-thirds of children younger than 3 years receive antibiotics during a year. Physicians prescribe mostly penicillins, but the proportion of broad spectrum penicillins is so high that enforcement of national guidelines should be reconsidered. The results from our study and others in Europe and the United States support the need for developing systematic surveillance of antibiotic use. The Danish National Health System, with the individualized drug utilization statistics, is a powerful tool in monitoring the individual use of antibiotics.

ACKNOWLEDGMENTS

The study was supported by The Medical Research Unit, Ringkjøbing County, by Helsefonden (Grant 11/284-96) and by the Danish Medical Research Council (Grant 9700677). The activities of the Danish Epidemiology Science Centre are financed by a grant from the Danish National Research Foundation.

The staff at the Department of Health Insurance and Preventive Medicine and Hospital Registries in the County of North Jutland are thanked for assistance in preparing the data for analyses.

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Keywords:

Antibiotics; children; drug utilization; prescription database; epidemiology

© 1999 Lippincott Williams & Wilkins, Inc.