a The Danish Epidemiology Science Centre at the Department of Epidemiology and Social Medicine, University of Aarhus, Aarhus C, Denmark b The Medical Research Unit, Ringkjøbing County, Denmark c The Clinical Epidemiological Research Unit, Aalborg Hospital, Aalborg, Denmark d Department of Clinical Microbiology, Aalborg Hospital, Aalborg, Denmark e Department of Internal Medicine V, Aarhus University Hospital, Aarhus C, Denmark
Abstract
The risk of receiving more than one prescription within an antibiotic course was examined for all children aged 0 to 5 years in a Danish county during 1997. We identified 29,307 prescriptions of systemic antibiotics for 16,245 children in a prescription database. Ten per cent of the prescriptions were followed by a new prescription within 10 days. In children who received two prescriptions (n = 3993), 19% redeemed the prescriptions within the same course. When the child was prescribed penicillin V, compared with broad-spectrum penicillin, the odds ratio of receiving a repeat prescription within 12 days was 2.9 (95% CI 2.53.4) and within 310 days 1.3 (95% CI 1.21.5).
Introduction
Knowledge about prescription patterns is necessary to improve the quality of prescribing.1 Twelve per cent of Danish children younger than 3 years received at least three prescriptions of systemic antibiotics during one year.2 Few studies have analysed to what extent the multiple prescriptions are caused by different infections or whether the risk of receiving more than one prescription in one antibiotic course depends on the type of antibiotic.3
We identified prescriptions of systemic antibiotics for all children aged 05 years in North Jutland County, Denmark, during 1997. The specific aims were (i) to analyse the types of antibiotic prescribed and estimate the number of prescriptions per child, (ii) to estimate the number of antibiotic courses per child per year in relation to total number of prescriptions and (iii) to estimate the risk of receiving a repeat prescription within 010 days in relation to type of antibiotic.
Materials and methods
Setting
We identified all reimbursed prescriptions of systemic antibiotics for children aged 05 years from 1 January 1997 to 31 December 1997 in the County of North Jutland. On 1 January 1997, the population of the county was 492,348 inhabitants (equivalent to about 9% of the Danish population), including 38,074 children aged 05 years. More than 98% of the Danish population are registered with a general practitioner and receive free medical care. The Danish National Health Service provides tax-supported health care for all citizens, and reimburses 5075% of the cost of most prescribed drugs. The data are transferred from the National Health Service to the Pharmacoepidemiological Prescription Database of the County of North Jutland, which has been described elsewhere.2
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 include cephalosporins and tetracyclines. The influence of reimbursement is negligible in this study because cephalosporins comprised only 0.2% of the total defined daily doses of antibiotics sold in the county during 1996 and tetracyclines are not used for children younger than 12 years.4,5
Analyses
We identified all prescriptions for systemic antibiotics (ATC code J01), classified into four groups: broad-spectrum penicillins (amoxycillin/pivampicillin/ampicillin/amoxycillin with enzyme inhibitor/bacampicillin/amidinopenicillin), penicillin V, macrolides and miscellaneous: sulphonamide-containing anti-infectives, other penicillins (dicloxacillin/flucloxacillin), quinolones and fusidic acid. Age refers to the child's age at the date of purchase of the first prescription in 1997.
The days between prescriptions for each child were calculated and grouped: no new prescription, 02 days, 310 days and more than 10 days. A repeat prescription was defined as a prescription preceded by a prescription within 010 days (one antibiotic course). In the estimations of risk of repeat prescription according to type of antibiotic, 949 prescriptions were excluded because they were purchased on the same day and we had no information about which prescription was purchased first. The distribution of antibiotic groups was equal in the excluded and included prescriptions.
Statistical analyses
We calculated the odds ratio (OR) to estimate the association between type of antibiotic (penicillinV, broad-spectrum penicillin) and repeat prescription within 12 or 310 days (yes/no). The ORs were adjusted for age and gender in logistic regression analyses using SPSS 8.0. Age was included in the model as a categorical variable: 01, 23, and 45 years. Adjusting for method of dispension, i.e. tablets or liquid, did not change the risk estimates, and was not included in the final model.
Results
We identified 29,307 prescriptions of systemic antibiotics for 16,245 children aged 05 years, of whom 53% were male. Broad-spectrum penicillins comprised 49%, penicillin V 38%, macrolides 10% and miscellaneous 3% of the prescriptions.
In children for whom antibiotics were prescribed, 56% received one, 24% received two and 20% received three or more prescriptions. The children who received at least three prescriptions were mainly the younger ones, i.e. 28% of children under 1-year-old, compared with 13% of 5-year-olds.
Estimation of number of antibiotic courses
Overall, 16,245 prescriptions were not followed by a new prescription, 1380 (5%) were followed by a repeat prescription within 02 days, 1426 (5%) within 310 days and 10,256 (35%) within 10354 days. The proportion of broad-spectrum penicillins was higher in the repeat prescriptions (53%) compared with the initial prescriptions (37%). Table I shows the number of antibiotic courses per child in relation to each child's total number of prescriptions.
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The risk within 12 days was almost three-fold when prescribed penicillin V, compared with broad-spectrum penicillin (Table II). Amoxycillin and pivampicillin accounted for 86% of the broad-spectrum penicillins. For pivampicillin, the OR for receiving a repeat prescription within 12 days and 310 days, compared with amoxycillin, was 2.8 (95% CI 1.94.2) and 1.8 (95% CI 1.42.4), respectively. No difference was found between the different proprietary names of amoxycillin.
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Discussion
A large proportion of children received more than one prescription within an antibiotic course. This was more likely to occur if the child initially was prescribed penicillin V, compared with broad-spectrum antibiotics.
The major strengths of our study are its large size, the population-based design and the data quality. Among the weaknesses are the lack of information about indications for prescribing and duration of treatment. Futhermore, the cut-off level when defining a repeat prescription (010 days) for an antibiotic course is arbitrary, although clinically relevant.
Our data support other reports of treatment of infections requiring more than one antibiotic prescription.3 The number of prescriptions seems to be an inaccurate measure of the number of antibiotic-treated infections in childhood. This should be considered when comparing the antibiotic use in different countries since patterns of repeat prescriptions may differ. Multiple prescriptions of antibiotics for children are prescribed either for different episodes of infections or repeatedly for the same infection, i.e. one acute episode or as prophylactic medication. The latter is not common in Denmark, and we found only 23 individuals with 10 prescriptions or more.
The repeat prescriptions at interval 02 days may be considered as overprescribing. The difference in risk in this period compared with 310 days suggest that the problem appears to be ease of administration and compliance rather than the efficacy of the medication. Moreover, the larger risk of repeat prescriptions with penicillin V compared with broad-spectrum penicillins is in accord with studies of palatability of antimicrobial suspensions; amoxycillin and ampicillin were preferred among the penicillins.6 The variation within proprietary names of penicillin V emphasizes the importance of acceptance; however, the analyses did not reveal any particular trend with respect to taste or formulation.
In our study repeat prescriptions result in increased use of broad-spectrum antibiotics. Firstly because the repeat prescription is most often a broad-spectrum preparation and secondly because previous experience with a drug may influence the future choice of drug.7 Increased antibiotic use exerts a selective pressure for the resistant strains among bacteria.8,9 The speed at which resistance develops increases with overprescribing, use of broad-spectrum drugs and poor compliance.10
Repeat prescription increases treatment costs both for the patient and the health care system owing to the expenses connected with repeated prescriptions and physician visits.3 Prolonging the treatment period may increase the frequency of side-effects and in general, broad-spectrum antibiotics have the largest frequency of side-effects.5
The Danish guidelines recommend penicillin V as the first-choice drug in respiratory tract infections in all age groups.5 Penicillin V is low-cost and has a low risk of resistance, but our study indicates some excess risk of overprescribing. We suggest increased attention to the compliance issue to maintain the restrictive antibiotic policy in Denmark as well as promoting this in other countries. The marked variation within different proprietary names of penicillin V emphasizes the need for the pharmaceutical industry to improve their efforts in producing well-tolerated products.
Acknowledgments
The staff at the Department of Health Insurance and Preventive Medicine and Hospital Registries in the County of Northern Jutland are mostly gratefully thanked for excellent assistance in preparing the data for analyses. The study was supported by The Medical Research Unit, Ringkjøbing County, and by the Danish Medical Research Council (grant No. 9700677). The activities of the Danish Epidemiology Science Centre are financed by a grant from the Danish National Research Foundation.
Notes
* Corrrespondence address. The Danish Epidemiology Science
Centre, University of Aarhus, Vennelyst Boulevard 6, 8000 Aarhus C, Denmark. Tel:
+45-8942-6111; Fax: +45-8613-1580; E-mail: nt{at}soci.au.dk
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Received 14 May 1999; returned 6 July 1999; revised 13 August 1999; accepted 24 August 1999