Main findings and interpretation
In the last decade, the number of packages of antibiotics for systemic use delivered in public pharmacies to children and associated NIHDI expenditures have decreased. New antibiotic prescribing guidelines [
21], several national antibiotic campaigns [
16], and some local initiatives such as communication skills training [
22] and discussing antibiotic prescription behaviour at local quality circles [
23], are associated with significantly declining antibiotic use for children in Belgium. The change of the reimbursement conditions in 2017 [
24] and 2018 [
25] and making it mandatory for the pharmacist to deliver the cheapest antibiotic [
26] have contributed to reducing NIHDI expenditures. Additionally, the difficulties associated with developing new antibiotics [
27], together with the expiration of patents of agents that did develop successfully, promotes that the cheaper, generic antibiotics represent a bigger portion of the market [
28]. As a consequence, the price of the original specialities must lower to compete with the generics [
29], suppressing NIHDI expenditures. An overall decreasing trend in antibiotic use and expenditures has been observed for other high-income countries, such as France [
30], Italy [
31], Germany [
32], and the Netherlands [
32].
Similar to other high-income countries [
30,
31,
33,
34], penicillins are in general the most commonly prescribed antibiotics for children. Alternations in prescribing guidelines, which is often a consequence of antimicrobial resistance and/or side effects [
35], drug shortages, and the rising co-payment of the patient for certain drug classes [
25] presumably result in shifts in use of the different antibiotic classes.
We found that most antibiotics are delivered during winter and the least during summer. During winter, there is a higher incidence of respiratory infections, which are mainly caused by viruses [
16]. These viral respiratory tract infections may lead to a secondary bacterial infection such as pneumonia or otitis media where an antibiotic is often justified [
2]. An Italian study observed the same seasonality pattern of prescriptions, which was shown to be in parallel with the trend of flu syndromes [
31].
Although declining in the past ten years, most antibiotics for children are still prescribed by GPs, followed by paediatricians. In the United States, it was also observed that family practitioners account for the highest number of outpatient antibiotic prescriptions, followed by paediatricians, internists, and dentists [
34]. However, they did not consider prescriptions for children separately. For paediatricians, the contribution of NIHDI expenditures is higher than for the number of packages. This implies that specialists in paediatrics prescribe more expensive drugs. Some children presenting to paediatricians require more specialistic, so more expensive, care, as they suffer from conditions such as asthma, leukaemia, immune deficiency, cystic fibrosis, and recurring urinary tract infections [
36]. Moreover, expensive, and often more toxic, alternative antibiotics must be used when pathogens become resistant to first-line therapy [
37]. We also found a significant increase in cost and number of antibiotic packages prescribed by specialists other than GPs or paediatricians (e.g., ear, nose, and throat physicians, pulmonologists, dermatologists, internal medicine specialists, and dentists) [
12]. Therefore, we hypothesize that antibiotic campaigns were less effective for these doctors. Besides, extensive antibiotic guidelines are less readily available for these doctors, compared to primary care physicians.
Although decreasing for all age categories, still more antibiotics are prescribed for younger children. This is as expected since younger children are more at risk of serious infections, requiring more cautious management [
38]. This is also observed in Italy [
31,
33], Denmark [
33], France [
30], and the United States [
34].
As with our study, geographic variations in antibiotic consumption have also been observed for Italy [
31] and the United States [
34].
Strengths and limitations
This is an in-depth analysis of recent antibiotic dispensing data for children in Belgium. Farmanet is a reliable source of antibiotic prescription data, as opposed to self-reporting by patients. This database contains enough detail regarding the age and place of residence of the child and the specialty of the prescribing healthcare professional. We used the number of packages as a proxy of antibiotic use, as DDD is not a suitable metric for children [
17].
Our research has some limitations as well. It is crucial to keep in mind that, given the data retrieved from Farmanet, exposure to antibiotics is underestimated because the practice of self-medication is unknown, i.e., the use of leftovers or drugs obtained from elsewhere (e.g., abroad, friends and family) [
39]. In fact, this could represent an important source of inappropriate antimicrobial use [
39]. Belgian antibiotic use is even more underestimated, as we did not consider the prescriptions of antibiotics for topical use and ophthalmologicals. These classes of antibiotics fall out of the scope of this research, namely diagnostic uncertainty in acutely ill children. On the other hand, it is impossible to estimate whether the patient took the prescribed drug and that it was taken as prescribed by the doctor (i.e., right dose, time of the day, and duration) [
40].
Moreover, our conclusions should be interpreted with caution, as correction for population growth and/or decline is imprecise. Farmanet calculates age as delivery year of the antibiotic minus birth year, overestimating the actual age of the children, while Statbel contains data for the first of January of each year. This means that data retrieved from Farmanet and Statbel cannot be perfectly aligned to perform trend analysis per 1000 inhabitants. However, correcting for alternations in the population allows generalisability to other settings.
Implications for research
This research is a critical step in identifying where antibiotic prescribing practices can be improved. Our data suggest that physicians working in Walloon region and rural areas prescribe more antibiotics per 1000 inhabitants. Besides, in the past ten years, other medical doctors than GPs and paediatricians have proportionally prescribed more antibiotics for children.
The lack of information about the indication the drug was prescribed for, the dosing frequency, and the duration of therapy, make it impossible to estimate whether the use of antibiotics was appropriate based on these data. Further research is needed to investigate the appropriateness of prescriptions.
Moreover, further research should investigate temporal trends of broad and narrow spectrum antibiotic use, as we did not provide data on the individual antibiotics. Physicians prescribe broad-spectrum antibiotics because of diagnostic uncertainty, stimulating antimicrobial resistance [
41]. This diagnostic uncertainty occurs for instance when the physician does not know whether the illness is of viral or bacterial origin or, when considered bacterial, which bacteria is the causative micro-organism.
Future studies should aim to analyse whether COVID-19 has had an impact on antibiotic use in Belgium. We hypothesize that, similarly to England [
42], the number of prescriptions will have declined, but when compared to the number of doctor’s appointments, this number is higher than expected. During COVID-19, there is a higher rate of remote/telephone consultations, leading to higher diagnostic uncertainty by which physicians tend to prescribe an antibiotic more easily [
42].