Main results
Between 1999 and 2005 the yearly prevalence of antibiotic use in children varied from 17.8 to 19.3%. The amount of antibiotic prescriptions for children calculated on a monthly basis fluctuated each year, with a peak around the winter months. Although the total number of antibiotic prescriptions per year did not change between 1999 and 2005, we did observe a shift in prescribing patterns. The prescribing of amoxicillin, the small-spectrum phenethicillin, which is a penicillin preparation, and the older macrolide erythromycin decreased, while the prescribing of amoxicillin with clavulanic acid and the new macrolides azithromycin and clarithromycin increased.
The use of flucloxacillin also showed an increasing trend, especially during the months of August and September. Trimethoprim was used less by the two younger age groups. There was a general trend for antibiotic drug use to be the highest in the youngest age group (0–4 years).
Literature comparison
An Italian study of 1998, which concentrated on children aged 0–15 years, showed that 46.4% of the children studied received at least one antibiotic prescription in that year [14]. In Scotland in 1999/2000, the prevalence of antibiotic use among 0- to 16-year olds was estimated at 14.2% [15]. In a Danish study that was based on a prescription database, the prevalence of antibiotic use was 29.0% in a group of 0- to 15-year olds. When we compare our data to those reported in these studies, the prevalence of prescribing antibiotics to children ≤19 years in the Netherlands is lower than that in Italy, slightly lower than that in Denmark, but higher than that in Scotland.
The study by Otters et al. is a cross-sectional study based on the National GP Survey and restricted to 1987 and 2001 [9]. Data were presented for children aged 0–17 years, and the yearly number of antibiotic prescriptions per 1000 children was determined. In 2001, this number was smaller than what we found in 2001 (232 vs. 307). Possible explanations for this difference could be the dissimilar age groups or the fact that the origin of the data is not the same—that is to say, GPs in the National Survey were aware of participation, which may have influenced their prescribing behaviour. However, our study shows that the trend described by the Otters study (an increase in the number of broad-spectrum antibiotic prescriptions) continued between 2001 and 2005.
The most commonly prescribed antibiotic drugs in our study were amoxicillin, amoxicillin with clavulanic acid and clarithromycin. This is comparable to the data obtained in the National Survey from 2001 [9]. In Germany and Denmark, the small-spectrum penicillin known as penicillin V was prescribed more often for children than the broad-spectrum penicillins [16, 17]. In Italy, cephalosporins and macrolides were prescribed the most [14] and in Scotland, amoxicillin, erythromycin and phenoxymethylpenicillin were the most commonly prescribed antibiotics [15]. It would appear that each country has its own preferences in terms of antibiotic drugs.
In our study, the prevalence of antibiotic use was highest in the youngest age group, and the lowest prevalence of users was found in the group of 10- to 14-year olds. In the National Survey, a similar distribution of antibiotic use was found [9]. Studies from Italy and Denmark used different age groups. Consequently, a direct comparison was not possible [14, 17].
Seasonal variation
The fluctuations during the year in the number of prescriptions per month peaking in the winter period and showing a nadir in the summer is similar to the results of a European study on adults [8] and possibly indicates that most antibiotic drugs are prescribed for respiratory infections. Figure 2 shows precisely this pattern for drugs used in treating respiratory infections (azithromycin, amoxicillin, erythromycin, clarithromycin and doxycyclin). In contrast, trimethoprim (Fig. 3), which is used for urinary tract infections, does not show this kind of fluctuation.
The August and September peaks of flucloxacillin use (Fig. 2) can be explained by an increase in the number of impetigo cases in children in the Netherlands, which usually occurs after the summer holiday when school starts again. This phenomenon is described in a study by GPs [18].
Changes over time
The changes in the prescribing patterns between 1999 and 2005, which show an evolution in prescribing behaviour from a preference for small-spectrum penicillin to one for amoxicillin/clavulanic acid, and from older to newer macrolides, have also been described in other Dutch studies [9, 19]. This shift could be linked to a number of circumstances. It is possible that the reports on increasing antibiotic resistance encouraged physicians to choose a broader and more safe approach to prescribing. The decrease in the use of erythromycin may be attributed to the fact that its use is associated with more side effects, worse pharmacokinetic properties and increased interactions with other drugs, in comparison to other macrolides. Azithromycin has the additional advantage of requiring a shorter course and having a more convenient dosage system as a liquid formulation. Clarithromycin is currently available in straws, which allows the child to take the drug by sucking it through the straw; this is a clever solution which may also be preferred by the prescribing physician.
The decreased use of trimethoprim in the second half of 2004, especially in younger age groups, can be explained by discontinuation of the product Monotrim, the only liquid formulation of trimethoprim available in the Netherlands [20]. There is an alternative in a pharmacy-based formulation, however, this takes some time to prepare. According to our results, most physicians choose to prescribe a different antibiotic. Nitrofurantoin may be an alternative to trimethoprim, but as this is not available as a liquid formulation either, the physicians may prefer amoxicillin with clavulanic acid or cotrimoxazole as an alternative for these age groups.
Comparison to Dutch guidelines
Acute respiratory infections and otitis media are the most frequently occurring infections in children. Data from the National Survey showed that in 2001 the yearly incidence of these two types of infections was 94.8 and 61.2 per 1000 children, respectively [21]. For a respiratory infection, both Dutch guidelines, the NHG and GF, recommend prescribing small-spectrum phenethicillin only in the case of a secondary bacterial infection. For otitis media, the preferred drug is amoxicillin.
Before starting treatment, it is advised to wait for 3 days to see if there’s no improvement—except when the patient is younger than 6 months. In case of a penicillin allergy, the second choice for both indications is clarithromycin [12, 13]. The large number of prescriptions for amoxicillin in this study (137.9/1000 in 2001) compared to those for phenethicillin (17.9/1000 in 2001), which are relatively few, is not in accordance with the indications for prevalence, suggesting that respiratory tract infections are possibly not treated with the preferred drug. It also appears that the guidelines' recommendation to pursue a restrained policy towards antibiotic prescribing is not being followed.
Accordingly, we conclude that the prescribing patterns in terms of prescribing antibiotic drugs for Dutch children ≤ 19 years old is not in agreement with the guidelines.
Limitations to the study
In this study the medical indications that motivated the physician to prescribe the drugs were not known as this information is generally not given to the pharmacy by the physician. The prescriptions used here were only dispensing data, so we did not know whether the patient actually did use the medication at home. Our data are merely an indication of how antibiotics are prescribed and used.
The prophylactic use of antibiotics, the prolongation of a course or the switch to another drug within a course because of allergy or side effects were all counted as separate prescriptions, even though they are actually part of one episode of use. Of all prescriptions, 85% were not followed by another antibiotic prescription within 1 month. Of the other 15%, some prescriptions may have belonged to the same clinical episode, which would suggest that we may have overestimated the number of antibiotic courses.
Over-the-counter medication is not included in our database. However, as antibiotic drugs are not allowed to be sold over-the-counter in the Netherlands, this does not represent a significant problem in our study.
Recommendations
The results of this study reveal that antibiotic prescribing for children in the Netherlands is far from optimal, which is similar to the situation in other countries.
Different ways have been investigated to improve guideline-directed prescribing of antibiotic drugs in children. One approach is to better educate the parents in antibiotic use, including explanations during visits to the doctor with the explicit aim of decreasing unnecessary prescribing [22–24]. Physicians could also be trained more thoroughly in this area. A strategy implemented in the UK—called ‘delayed prescribing’ (i.e. a required delay of a few days before starting an antibiotic course)—has reduced the prescribing rates for antibiotic drugs without causing the number of hospital admissions due to complications to increase [25–27]. The Dutch guidelines already have recommended following this strategy for otitis media [12]. The development of a clinical decision rule for respiratory infections can reduce inappropriate prescribing of antibiotic drugs [6]. A similar decision rule has been developed in public hospitals in Brazil, where they look at the symptoms to separate viral and bacterial respiratory infections, thereby preventing 41–55% of unnecessary antibiotic prescriptions.
Conclusion
On the basis of the results reported here, it would appear that the image of the Netherlands being a country with a restrained policy towards prescribing antibiotic drugs is not entirely applicable when it concerns children. Not only were broad-spectrum antibiotic drugs prescribed more frequently than recommended by the guidelines, but it also appears that a shift took place to broader prescribing between the years 1999 and 2005. This is an undesirable development as it could contribute to antibiotic resistance.
We found that the choice of drugs can be influenced by events such as the unavailability of the drug as a liquid formulation (thrimethoprim) or the increased occurrence of a specific indication (impetigo and flucloxacillin).
Our results demonstrate that an improvement of guideline-directed antibiotic prescribing is needed in the Netherlands.