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Rinnakkaistallenteet Terveystieteiden tiedekunta
2019
Outpatient antibacterial use and costs in children and adolescents: a
nationwide register-based study in Finland, 2008-16
Parviainen, Sofia
Oxford University Press (OUP)
Tieteelliset aikakauslehtiartikkelit
© Authors
All rights reserved
http://dx.doi.org/10.1093/jac/dkz208
https://erepo.uef.fi/handle/123456789/7743
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Outpatient antibacterial use and costs in children and adolescents: a na-
1
tionwide register-based study in Finland, 2008
–2016
2 3
Sofia PARVIAINEN1 MSc (Pharm.), Leena SAASTAMOINEN2* PhD (Pharm.), Adjunct 4
Professor, Senior Researcher, Anneli LAUHIO3 MD, PhD, Adjunct Professor, Senior Medi- 5
cal Advisor, Specialist in infectious diseases, Kati SEPPONEN1 PhD (Pharm.), Senior Lec- 6
turer 7
8
1School of Pharmacy, Faculty of Health Sciences, University of Eastern Finland, Kuopio, 9
Finland 10
2The Social Insurance Institution of Finland (Kela), Research Group, Helsinki, Finland 11
Tel.: +358206341972 12
e-mail: leena.saastamoinen@kela.fi 13
3The Social Insurance Institution of Finland (Kela), Benefit Services, Helsinki, Finland 14
15
*Corresponding author 16
Running title: Antibacterial use and costs in 0-17 year olds 17
18
Abstract
19 20
Objectives: To describe the prevalence of outpatient use and the costs of systemic antibacte- 21
rials among children and adolescents in Finland in 2008–2016 and to examine patterns of use 22
by age and gender.
23
Methods: Data were retrieved from the Finnish statistical database Kelasto based on the 24
Finnish Prescription Registry. Data included information on dispensed reimbursed prescrip- 25
tions of antibacterials for systemic use in children aged 0–17 years in 2008–2016. Prevalence 26
of antibacterial prescriptions per 1,000 children and costs per prescription were calculated.
27
Results: The overall prevalence of antibacterial prescriptions decreased in the study period 28
and was highest in 2010 with 708 prescriptions per 1,000 children, and lowest in 2016 with 29
374 prescriptions per 1,000 children. Children aged 1–2 years had the highest prevalence of 30
antibacterial prescriptions. Furthermore, boys had slightly higher prevalences than girls. The 31
ten most used antibacterial agents covered 97% of all prescriptions, and broad-spectrum peni- 32
cillins were the most used antibacterials. The total costs of antibacterials decreased during the 33
study period but the costs per prescription increased.
34
Conclusions: This study showed a decreasing trend in the prescribing of antibacterial drugs 35
regardless of age or gender. Increasing awareness of antimicrobial resistance, reimbursement 36
status changes and pneumococcal and influenza vaccinations are possible reasons for this.
37
Some of the antibacterial oral solutions lost their reimbursement status but their consumption 38
did not decrease any faster than the consumption of the substances with continuous reimburs- 39
ability. It is likely that removing the antibacterials’ reimbursement status placed an extra cost 40
burden on families and increased costs per prescription.
41 42
Introduction
43 44
Antimicrobial resistance is a global health problem causing unnecessary costs and increased 45
morbidity due to antibacterials being no longer effective in infectious diseases which used to 46
be easily treatable. The WHO and the European Commission have both launched action plans 47
on fighting antimicrobial resistance. 1,2 Based on them, Finland has also launched a National 48
Action Plan on Antimicrobial Resistance for 2017–2021.3 It emphasises the importance of 49
considering humans, animals, plants, food and the environment in the prevention of antimi- 50
crobial resistance, and also states the need for research in the field of antimicrobial resistance 51
and antimicrobial consumption in order to provide information for decision making and 52
fighting antimicrobial resistance.
53
In Europe, antibacterial use varies greatly between countries and is the highest in southern 54
Europe.4 In Finland, the use of antibacterials is slightly below the average of all European 55
countries but higher than in the other Nordic countries apart from Iceland. The National Ac- 56
tion Plan also acknowledges this and sets a goal to reduce antibacterial use to the same level 57
with the other Nordic Countries.3 In children, the prevalence of antimicrobial use has been 58
reported to be high in Italy and Canada and low in the Netherlands and the UK.5 59
60
Antibacterial use is most common among young children, respiratory tract infections being 61
the most common indication.5,6 It has been estimated that approximately half of the antibacte- 62
rials prescribed for respiratory tract infections are unnecessary.6 Therefore, there is potential 63
for decreasing antibacterial use in children.There is only a limited amount of recent compara- 64
ble information available on the prevalence of antibacterial use in children and trends over a 65
long period of time. Also, to the best of our knowledge, only one register-based study in Fin- 66
land briefly described trends in paediatric antibacterial use in 2006–2011.7 It stated that the 67
proportion of children who used systemic antibacterials increased by 6% in 2008–2011. In 68
addition, information on the costs of antibacterial drugs is needed in order to evaluate the cost 69
burden for families.
70 71
The aim of this nationwide register-based study was to determine the prevalence of outpatient 72
antibacterial prescribing, antibacterial costs and reimbursement changes in children and ado- 73
lescents in Finland by age and gender in 2008–2016.
74 75
Materials and methods
76 77
Ethics 78
According to Finnish legislation, this study did not need ethical approval since it includes 79
only register data in aggregate statistics format and individuals cannot be identified.
80 81
Setting 82
In Finland, public primary healthcare services are free for children under 18 years of age, and 83
outpatient prescription medicine expenses are partly covered by the Social Insurance Institu- 84
tion, which is an independent social security institution responsible for implementing the re- 85
imbursement system.8 There are three reimbursement categories: basic refund of 40%, lower 86
special refund of 65% and higher special refund of 100% in which the patient pays only a 87
copayment of 4.50 euros per medicine.9 Special reimbursement status can be granted only for 88
specifically defined severe and chronic diseases. In Finland, all antibacterials require a pre- 89
scription and have the basic reimbursement status, although some are non-reimbursable.
90
However, approximately 52% of the families with children have an additional private insur- 91
ance which also covers medicine expenses not covered by the Social Insurance Institution.10 92
93
Data source and data collection 94
Information on systemic antibacterials (ATC code J01) prescribed and dispensed for children 95
under 18 years of age in 2008–2016 was retrieved from the statistical database Kelasto admin- 96
istered by the Social Insurance Institution.11 The data on prescriptions is based on the Finnish 97
Prescription Registry and it contains information on all reimbursed drugs dispensed in phar- 98
macies in Finland. In Kelasto, drugs are classified according to the Anatomic Therapeutic 99
Chemical (ATC) classification system.12 Besides the ATC code, the information includes the 100
name of the active substance, the number of dispensed reimbursed prescriptions, the number 101
of reimbursement recipients, total costs and reimbursement costs as well as the age and gen- 102
der of the patient. Information on the indication or dosage of prescribed drugs is not available.
103
In addition, consumption data of antibacterial oral solutions was retrieved from the Finnish 104
Medicines Agency. This data included also non-reimbursable antibacterials (reported as de- 105
fined daily doses/1,000 inhabitants/day).
106 107
Kelasto also contains information on the number of persons who have the right to social in- 108
surance in Finland according to the Health Insurance Act (1124/2004).13 This includes all 109
residents in Finland, and the reimbursement is deducted from the price directly at the pharma- 110
cy. We retrieved information on the number of all insured children aged 0–17 years in 2008–
111
2016. This number had a downward trend, being 1 091 505 in 2008 and 1 072 341 in 2016.
112
Approximately 49% of the insured were girls.
113 114
Analysis 115
Microsoft Excel (Release 16.9, Microsoft 2017) was used to analyse the data. The prevalence 116
of antibacterial use was expressed as a number of prescriptions per 1,000 children per year.
117
Trends in the prevalence of antibacterial use were observed by age in the age groups <1, 1–2, 118
3–6, 7–11 and 12–17 years and by gender. Ten most commonly used antibacterial agents were 119
chosen based on the total number of antibacterial prescriptions during the whole study period 120
and the changes in their prescription rates were analysed more closely. The changes in the 121
reimbursement status of oral solutions were analysed in the Finnish Medicines Agency’s data 122
on total consumption of oral solutions by comparing the consumption of antibacterial agents 123
with and without reimbursement cut off.
124 125
Results
126
The proportion of children who used systemic antibacterials decreased during the study peri- 127
od, from 35% in 2008 to 24% in 2016. The proportion was highest (37%) in 2010. The total 128
number of antibacterial prescriptions varied between 767,905 in 2010 and 400,860 in 2016.
129
During the whole study period the prevalence of antibacterial prescriptions decreased by 43%, 130
being 660 prescriptions per 1,000 children in 2008 and 374 prescriptions per 1,000 children in 131
2016 (Table 1). The decrease was seen in children of all ages and both genders. However, the 132
prevalence of antibacterial prescriptions increased in 2010 in children of all ages and both 133
genders.
134 135
Figure 1 shows differences in the prevalence of antibacterial prescriptions per 1,000 children 136
in the years 2008, 2012 and 2016 in different ages. The prevalence was highest in children 137
aged 1–2 years and after that decreased gradually. After the age of 12 years the prevalence of 138
antibacterial prescriptions slightly increased again. The pattern was similar in all study years.
139 140
Antibacterial use by age and gender 141
Children aged 1–2 years had the highest prevalences in all study years, while children under 142
the age of 1 had the lowest prevalences (Table 1 and Figure 2a). The difference by age was 143
most prevalent in 2008–2010: children aged 1–2 years had approximately a four times higher 144
prevalence of prescriptions than children aged 12–17 years. In 2016, the difference had nar- 145
rowed: children aged 1–2 years had approximately twice as many prescriptions than children 146
aged 12–17 years. The prevalence of antibacterial prescriptions was slightly higher in boys 147
than girls in all study years (Table 1 and Figure 2b). However, the difference was small and 148
narrowed during the study period (Table 1).
149 150
The ten most used antibacterial agents 151
The ten most used antibacterial agents covered approximately 97% of all antibacterial pre- 152
scriptions in all study years. The prevalence of amoxicillin prescriptions was highest through- 153
out the study period (Figure 3), and amoxicillin prescriptions accounted for at most 48% of 154
the prescriptions in 2016. The proportion was lowest (33%) in 2011. In 2008–2014, cefalexin 155
prescriptions were the second most common, and they were replaced by the amoxicillin- 156
clavulanic acid combination in 2015–2016.
157 158
A decreasing trend in the prevalences of antibacterial agent prescriptions was detected. When 159
looking at the whole study period and comparing prevalences in 2008 and 2016, a decrease 160
was seen for all antibacterial agents except doxycycline and lymecycline, which had a low 161
prescription rate. However, the number of prescriptions slightly increased in 2010 for all anti- 162
bacterial agents except tetracycline.
163 164
The prevalence of amoxicillin prescriptions was highest in 2010 (252 per 1,000 children) and 165
lowest in 2016 (179 per 1,000 children), accounting for a decrease of 29%. The prevalence of 166
prescriptions for the amoxicillin-clavulanic acid combination was also highest in 2010 (95 167
prescriptions per 1,000 children) and lowest in 2016 (62 prescriptions per 1,000 children), 168
accounting for a 35% decrease. The prevalence of cefalexin prescriptions decreased markedly 169
as well by 66%, from 107 per 1,000 children in 2010 to 36 per 1,000 children in 2016, which 170
is partly due to reimbursement status changes of oral solutions of cefalexin in 2013 and 2014 171
(Table 2). The prevalence of azithromycin and clarithromycin prescriptions were highest in 172
2011 (100 per 1,000 children and 24 per 1,000 children, respectively), but since then both 173
have decreased by 61% and 73%, respectively. The prevalence of the sulfadiazine- 174
trimethoprim combination decreased from 58 prescriptions per 1,000 children in 2010 to 0 175
prescriptions per 1,000 children in 2014 due to a reimbursement cut off. Phenoxymethylpeni- 176
cillin prescriptions decreased gradually every year with a total decrease of 60% and the preva- 177
lence of prescriptions varying between 54 and 22 prescriptions per 1,000 children in 2008 and 178
2015.
179 180
Costs of antibacterials 181
The total costs of outpatient systemic antibacterial drugs for children aged 0–17 years were 182
10.9 million euros in 2008 and 7.3 million euros in 2016. Highest total costs were observed in 183
2011, when they were 11.6 million euros. The cost per prescription increased during the study 184
period from 15.15 euros per prescription in 2008 to 18.28 euros in 2016, accounting for a 185
21% increase. In the ten most used antibacterial agents, the costs per prescription for the sul- 186
fadiazine-trimethoprim combination, doxycycline, clarithromycin, amoxicillin and the amoxi- 187
cillin-clavulanic acid combination increased (Figure 4). Sulfadiazine-trimethoprim combina- 188
tion costs per prescription almost 4-foldedbetween 2013 and 2014 and remained at the same 189
level after that. Doxycycline costs increased by 59% between 2008 and 2016. Amoxicillin 190
costs per prescription increased by 25 % between 2008–2016, as well as did the clarithromy- 191
cin costs. In addition, amoxicillin-clavulanic acid combination costs per prescription in- 192
creased in 2009–2016 by 20%.
193 194
The increase in costs per prescription was seen in all ages and both genders (Figure 5). When 195
comparing the age groups, costs per prescription were the highest in children aged 3–6 years 196
(20.12 euros) and lowest in children under 1 year of age (14.60 euros) in 2016. The boys had 197
slightly higher costs, but the difference to girls was at most only 0.53 euros per prescription in 198
2016.
199 200
Changes in reimbursement status of oral solutions of ten most used antibacterial agents 201
Oral solutions of cefalexin, phenoxymethylpenicillin and the sulfadiazine-trimethoprim com- 202
bination lost their reimbursement status during the study period (Table 2). The overall preva- 203
lence of prescriptions may be underestimated due to this fact since the non-reimbursed pre- 204
scriptions do not appear in the Prescription Registry. However, according to consumption data 205
received from the Finnish Medicines Agency, the consumption of sulfadiazine-trimethoprim 206
combination oral solutions decreased in 2011–2016. Also, a decrease in the consumption of 207
oral solutions with no change in reimbursement status during the study period was seen when 208
comparing the years 2008 and 2016.
209
Discussion
210 211
The prevalence of antibacterial prescriptions in children and adolescents decreased during the whole 212
study period. The prevalence was highest among children aged 1–2 years and decreased with age.
213
Furthermore, boys had slightly higher prevalences of antibacterial prescriptions in all study years.
214
Amoxicillin was the most commonly used antibacterial agent throughout the study while cefalexin 215
was the second most common in 2008–2014 and the amoxicillin-clavulanic acid combination in 216
2015–2016. The costs of antibacterials per prescription increased during the study period. Some 217
oral solutions lost their reimbursement status, and were therefore not shown in our results. Howev- 218
er, the reimbursement cut off did not usually seem to affect the consumption in the year after the 219
reimbursement change. These factors increase the out-of-pocket costs of the families.
220 221
Our results show a decrease of 43% in the total prevalence of antibacterial prescriptions between 222
the years 2008 and 2016. A decrease this prominent has been previously reported in Sweden in 223
1992–2002 in children under 7 years of age (34% decrease),14 and in antibacterials prescribed for 224
the treatment of respiratory tract infections in 2008–2013 in children under 19 years of age (51%
225
decrease).15 Also, a 50% decrease was reported in France in 2001–2010 and a 21% decrease in 226
Greece in 2010–2013 in children under 19 years of age.16,17 There are many possible reasons for the 227
decrease in the prevalences of antibacterial prescriptions in our study. A crucial factor is the wide 228
recognition of antimicrobial resistance as a global threat, which has led to action plans being adopt- 229
ed and efforts taken to reduce antibacterial use.1,2 However, we don’t have robust evidence about 230
the influence of the awareness in prescribing in Finland. Before our study time, in 1998–2003, there 231
was a national program (MIKSTRA) to steward antimicrobial use in Finland, which improved the 232
quality of antimicrobial prescribing, but did not decrease the percentage of patients receiving anti- 233
microbial prescription18. The National Action Plan on Antimicrobial Resistance 2017–2021 for Fin- 234
land was published in May 2017, and thus it has not had effect on antimicrobial prescribing during 235
our study time as the planned prescribing guideline for antimicrobial prescribing in ambulatory care 236
has not yet been issued3. However, between MIKSTRA-program and National Action Plan, the 237
guidelines created during MIKSTRA have been updated and discussion and articles in medical and 238
common journals have probably increased awareness of antimicrobial resistance in Finland. In 239
2016, a guideline collecting together correct antimicrobial alternatives in most common infections, 240
was published19. 241
242
Also, changes in antibacterial drugs’ reimbursement status may have an effect on the results of this 243
study but it is most likely minor since only few oral solutions lost their reimbursement status. Fur- 244
thermore, the trend was downward already before 2014 when most of the reimbursement changes 245
occurred. Also, changes in epidemic situations affect the results: for example, the increase in the 246
number of amoxicillin, azithromycin, clarithromycin and doxycycline prescriptions in 2010 and 247
2011 may be explained by a mycoplasma epidemic, since the first-line treatments for pneumonia 248
caused by Mycoplasma pneumoniae are macrolide and doxycycline.20,21, 22 This has also been stated 249
previously as a possible reason for increased antibacterial use in those years.7 After the mycoplasma 250
epidemic, azithromycin use decreased, which might be due to a decrease in chlamydia cases in the 251
age group of 15–19 years in which azithromycin is the first-line treatment.20,23 Furthermore, a 252
pneumococcal conjugate vaccine was introduced to the Finnish National Vaccination Programme in 253
2010 and it has been reported to have reduced outpatient antimicrobial prescriptions for acute otitis 254
media (AOM). 24 Also, in Finland influenza vaccination was introduced to the National Vaccination 255
Programme for 6–36-month-old children in 2007 and it has also been reported to decrease the prev- 256
alence of AOM.25 257
258
The prevalence of antibacterial prescriptions in our study in 2008 (660 prescriptions per 1,000 chil- 259
dren) was approximately the same as in Canada in 2003 (608) and the US in 2013 (813).26,27 It was 260
higher than in the Netherlands in 2012 (262), Denmark in 2003 (385) and the UK in 2007 (568) but 261
lower than in Germany in 2006 (709) and Greece in 2010–2013 (average 1,100 per year).17,26, 28–30
262
In 2016, only the Netherlands had a lower prevalence (262) than the prevalence in our study (374 263
prescriptions per 1,000 children).28 However, the prevalences in all of the studies are from different 264
years and are therefore not directly comparable. Previously, surveys have also been conducted on 265
paediatric antibacterial use: in 2007, 3% of children aged 0–11 years used antibacterial drugs at the 266
moment of answering the survey,31 and in 2007 and 2008, 39% of children aged 0.5–15 years had 267
received at least one antibacterial drug prescription annually.32 This is similar to our result, 35%, in 268
2008. Also, one register-based study had similar results in children aged 0–15 years, 35% in 2008 269
and 37% in 2011.7 270
271
In our study, children aged 1–2 years had the highest prevalence of antibacterial prescriptions. It has 272
also been previously reported that young children are prescribed more antibacterials and the pre- 273
scribing decreases with age which is consistent with our results.15,17,26–36 As regards differences be- 274
tween genders, in our study boys used more antibacterials than girls. Three previous studies report- 275
ed that boys aged 0–4 years used more antibacterials than girls but after this age girls used more 276
antibacterials than boys.29,30,36 However, in the Netherlands and the US girls aged 0–19 years used 277
more antibacterials than boys.27,33 Our results show that broad-spectrum penicillins, combinations 278
of penicillins and macrolides were the most used antibacterial drugs in 2015 and 2016. Broad- 279
spectrum penicillins were also the most frequently used antibacterials in Canada, Denmark, France, 280
Germany, the Netherlands, the UK and the US.16,26,27,30,33,35,36 In Norway and Sweden, however, the 281
most used antibacterials were beta-lactamase sensitive penicillins, broad-spectrum penicillins and 282
macrolides,14,15,34 which differs from our results.
283 284
The increase in antibacterial costs per prescription may be due to an increase in the prescribed dose, 285
an increase in prices or a shift in use to more expensive products. In the Finnish reference price sys- 286
tem, the price notifications are submitted by the Marketing Authorisation Holders and the prices are 287
determined on a quarterly basis.9 In these occasions, the prices may change. In addition, for exam- 288
ple the reimbursement status of sulfadiazine-trimethoprim combination oral solutions was removed 289
and the only remaining reimbursed product was an expensive 100-tablet product which increases 290
the cost per prescription shown in our results.
291 292
Strengths and limitations 293
The main strength of this study is that it is nationwide and covers all children resident in Finland.
294
Also, the study period was fairly long, 9 years, which provides a comprehensive idea on the trends 295
in the prevalences of antibacterial prescriptions and cost changes through time. The main limitation 296
of our study is that it does not include non-reimbursable antibacterials. Therefore, the number of 297
prescriptions is most likely somewhat underestimated, but we tried to control this uncertainty by 298
taking into account the reimbursement status changes in oral antibacterial solutions. Anyhow, 299
changes in reimbursement status may cause changes in the data used. Furthermore, there is no data 300
on dosage or indication of the drugs, and whether or not the drugs were actually used even though 301
they were purchased. Therefore, we could not evaluate the appropriateness of antibacterial prescrib- 302
ing.
303 304
Conclusions 305
In conclusion, this study provides important estimates on the prevalence of use and costs of antibac- 306
terials in children and adolescents in Finland. It also shows a decreasing trend in the prescribing of 307
antibacterials in all ages and both genders. The decrease shown in our study could be due to grow- 308
ing awareness of the threat of antimicrobial resistance as well as the implementation of action plans.
309
Also, pneumococcal conjugate and influenza vaccinations and reimbursement status changes could 310
be factors affecting the decrease. However, it is likely that families have got an extra cost burden 311
due to an increase in antibacterial costs per prescription and reimbursement cut offs. Further studies 312
are needed to determine the cost burden to families more closely. Also, studies considering the ap- 313
propriateness of antibacterial prescribing and the prevalence of outpatient antibacterial use in the 314
adult population in Finland should be conducted in order to provide up to date information on the 315
trends of antibacterial use.
316 317
Acknowledgements
318 319
This study was part of a master’s thesis conducted in the School of Pharmacy, University of Eastern 320
Finland. The study was conducted in co-operation with the Social Insurance Institution of Finland 321
(Kela). We thank the Finnish Medicines Agency for providing us the antibacterial consumption 322
data.
323 324
Funding
325 326
This study was carried out as part of our routine work.
327 328
Transparency declarations
329 330
None to declare.
331 332
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Norway. J Antimicrob Chemother 2007; 59: 971–6 420
35 Lusini G, Lapi F, Sara B et al. Antibiotic prescribing in paediatric populations: a comparison 421
between Viareggio, Italy and Funen, Denmark. Eur J Public Health 2009; 19: 434–8 422
36 Pottegård A, Broe A, Aabenhus R et al. Use of antibiotics in children: a Danish nationwide drug 423
utilization study. Pediatr Infect Dis J 2015; 34: 16–22 424
425
Tables 426
427
Table 1. Prevalence of antibacterial drug prescriptions per 1,000 children per year.
428
Number of prescriptions/1,000 children/year
2008 2009 2010 2011 2012 2013 2014 2015 2016 Gender
Boys 677 614 726 721 634 521 516 413 380
Girls 644 586 689 687 612 500 496 395 367
Age groups (years)
<1 375 312 376 354 299 220 226 185 137
1–2 1,590 1,423 1,634 1,509 1,375 1,068 1,039 846 728
3–6 972 839 989 976 885 706 684 506 447
7–11 463 412 503 516 437 371 380 296 290
12–17 386 388 446 467 398 352 355 313 317
Total 660 601 708 704 623 511 506 404 374
Table 2. The reimbursement status and consumption of antibacterial oral solutions that belonged to the group of ten most commonly used antibacterial agents 429
in 2008–2016.
430
Consumption of oral solutions DDDs/1,000 children/day (change from previous year, %)
Antibacterial agent Reimbursement status of oral solutions 2008 2009 2010 2011 2012 2013 2014 2015 2016
J01CA04 Amoxicillin Reimbursable 0.469 0.417 0.509 0.478 0.445 0.425 0.467 0.431 0.404
(−11) (+22) (−6) (−7) (−4) (+10) (−8) (−6) J01CE02 Phe-
noxymethylpenicillin
Reimbursable 2008–03/2014, non-reimbursable 04/2014–2016
0.050 0.037 0.044 0.045 0.044 0.039 0.041 0.038 0.042 (−27) (+20) (+1) (0) (−12) (+3) (−7) (+12) J01CR02 Amoxicillin-
clavulanic acid combination
Reimbursable 0.208 0.195 0.244 0.236 0.224 0.198 0.221 0.193 0.163
(−6) (+25) (−4) (−5) (−11) (+12) (−13) (−16) J01DB01Cefalexin 2008–03/2013 reimbursable, 04/2013–11/2014
part of products non-reimbursable, 12/2014–2016 non-reimbursable
0.105 0.097 0.111 0.110 0.108 0.114 0.116 0.106 0.107 (−8) (+15) (−1) (−2) (+6) (+1) (−8) (+1) J01EE02 Sulfadiazine-
trimethoprim combination
Reimbursable 2008–01/2013 except for one oral solution in 2008–02/2010, non-reimbursable 02/2013–2016
0.084 0.079 0.088 0.087 0.078 0.073 0.069 0.062 0.052 (−7) (+13) (−2) (−11) (−6) (−6) (−9) (−17) J01FA09 Clarithromycin Reimbursable in all years except for one oral
solution in 2008–01/2013
0.036 0.029 0.038 0.066 0.041 0.030 0.029 0.021 0.020 (−18) (+31) (+72) (−38) (−28) (−1) (−27) (−7)
J01FA10 Azithromycin Reimbursable 0.097 0.084 0.088 0.104 0.083 0.062 0.059 0.048 0.039
(−13) (+5) (+18) (−20) (−25) (−6) (−17) (−20) 431
Figures 432
433
434 Figure 1. Prevalence of antibacterial prescriptions per 1,000 children for children aged 0–17 years in 2008, 435
2012 and 2016.
436 437 438 439 440 441 442 443 444 445 446 447 448 449
Figure 2. Trends in the prevalences of antibacterial prescriptions per 1,000 children in 2008–2016. (a) 450
Prevalence by age group. (b) Prevalence by gender and in total.
451 452 453
454
Figure 3. Prevalences of ten most used antibacterial agents (prescriptions per 1,000 children per year) in 455
2008–2016.
456 457
458 Figure 4. Costs of ten most used antibacterials per prescription in 2008–2016.
459 460 461 462 463 464 465 466 467
Figure 5. Costs of all antibacterials per prescription in 2008–2016. (a) Costs per prescription by age group.
468
(b) Costs per prescription by gender and in total.
469
470 471 472