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Journal of Antimicrobial Chemotherapy (1999) 43, 243–252
Surveillance of the overall consumption of antibacterial drugs in
humans, domestic animals and farmed fish in Norway in 1992 and 1996
Kari Gravea, Egil Lingaasb, Marit Bangenc and Marit Rønningd
a
Department of Veterinary Pharmacy and cVeterinary Drug Information Centre, The National Hospital
Pharmacy, Pilestredet 32, N-0027/Department of Pharmacology, Microbiology and Food Hygiene,
Norwegian College of Veterinary Medicine, PO Box 8146 Dep., N-0033 Oslo; bThe National Hospital,
Department of Hospital Infection Control, Pilestredet 32, N-0027 Oslo; dNorwegian Medicinal Depot AS,
PO Box 100 Veitvet, 0518 Oslo, Norway
The annual overall consumption of antibacterial drugs in Norway, categorized into human use,
use in domestic animals and in farmed fish, was estimated from wholesaler and feed-mill sales
statistics. Comprehensive data on drug consumption in human medicine in Norway are published on a regular basis on behalf of the drug authorities. These data, including use of antibacterial drugs, are expressed as the number of defined daily doses (DDD)/1000 inhabitants/
year. DDD cannot be employed to compare antibiotic consumption in human and veterinary
medicine as it is possible to calculate such data for only a few veterinary drugs. The only
parameter for which data are generally available, so far, is the amount used in kilograms of
active substance, which is the unit of measurement chosen in this study. It was found that
annual overall sales of antibacterial drugs in Norway, including antibacterial and ionophore
feed additives, decreased from 77 tonnes in 1992 to 49 tonnes in 1996, a 37% reduction. The use
in 1996 in human medicine, animals and farmed fish was 35 tonnes, 13 tonnes and 1 tonne,
respectively. While the annual amounts used in human medicine remained unchanged from
1992 to 1996, therapeutic use in fish farming declined by 96%. In domestic animals, therapeutic
use and use as feed additives declined by 17% and 5%, respectively. During the study period,
the size of the human and domestic animal populations at risk remained almost constant, while
the biomass (weight) of farmed fish at risk increased by >100%. This implies that both the absolute and relative consumption of antibacterial drugs in Norway decreased substantially during
the study period. The use of antibacterial drugs, both in humans and in domestic animals, has
changed in favour of penicillins, this being in accordance with general recommendations. The
reduction in the use of antibacterial drugs in farmed fish has been almost solely due to the
introduction of oil-adjuvanted vaccines against furuncolosis. It is concluded that the decline in
the amount of antibacterial drugs used in domestic animals, and the changes with regard to
choice of drugs, could be mainly attributed to changes in prescribing behaviour following
advice and recommendations. Moreover, the overall use of antibacterial drugs in Norway is
very low compared with that in most other countries and has been significantly reduced during
the 1990s.
Introduction
The association between increased rates of antibacterial
drug use and antibacterial drug resistance has been
documented for nosocomial infections and communityacquired infections1,2 as well as following veterinary use for
therapy and growth promotion. Selective pressure exerted
*Tel:
by widespread antibacterial drug use is the driving force in
the development of antibacterial drug resistance. Moreover, resistance factors in human and animal pathogens and
commensals, particularly those carried on mobile genes,
can spread rapidly within human and animal populations
and from animals to humans.3,4 As resistance develops in
rough relation to the extent of use, its emergence and
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243
© 1999 The British Society for Antimicrobial Chemotherapy
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K. Grave et al.
spread should be prevented primarily by limiting the use of
antibiotics.
Comprehensive data on drug consumption in human
medicine in Norway are published on a regular basis on
behalf of the drug authorities.5 These data, including use of
antibacterial drugs, are expressed as the number of defined
daily doses (DDD)/1000 inhabitants/year. For antibacterial
drugs, these data provide a basis for the evaluation of
therapeutic trends in bacterial infections and of human
exposure to antibacterial drugs. In veterinary medicine, it is
only possible to calculate such data for a small range of
veterinary antibacterial drugs and animal species.6 Hence,
the use of DDD to compare human and veterinary prescribing patterns is not possible. Data on antibacterial drug
consumption in humans in Norway in terms of kilograms of
active substance are not yet available. Comparable data
on antibacterial drug use in human medicine, domestic
animals and farmed fish are therefore lacking.
Both quantitative and qualitative records of antibacterial drug use are essential, not only to enable evaluation
of the impact of antibiotic policy, but also to allow the
determination of possible correlations between the use of
certain groups of antibacterial drugs and the emergence of
resistance (resistance-epidemiology). The main aims of this
study were to develop a comparative method to quantify
the overall use of antibacterial drugs in humans, domestic
animals and farmed fish in Norway, and to analyse trends in
the prescribing patterns of these drugs based on consumption in 1992 and 1996.
Materials and methods
In Norway, antibacterial drugs for therapeutic use in
humans, domestic animals and farmed fish are prescription
drugs only. Moreover, both human and veterinary antibacterial drugs have to be dispensed through pharmacies
which are supplied solely by drug wholesalers. Hospitals
have to be supplied either by pharmacies or wholesalers.
An exemption from the pharmacy/wholesaler monopoly
has been granted for medicated feed (i.e. feeds into which
drugs for therapeutic use are mixed before sale). Medicated feeds have to be prescribed by veterinary surgeons,
and are produced and delivered by feed mills authorized by
the Directorate of Health. In Norway, medicated feeds
produced and supplied by feed mills are used only in
farmed fish, not in livestock (Thorvik, T., personal communication). The reason for this practice is the small size of
livestock herds in Norway, compared with most other
European countries. However, herd/flock treatment of
other livestock with antibacterial drugs is possible, again
subject to veterinary prescription, with drugs being administered either through drinking water or in medicated feed
prepared on the farm.7
In Norway, the sales figures of drugs from wholesalers
and feed mills roughly equals the use of drugs (see Discus-
sion). In this study, antibacterial drug use is therefore used
as a synonym for sales figures of antibacterial drugs.
Overall sales data, representing sales from the Norwegian drug wholesalers to pharmacies and hospitals and
from feed mills to fish farms, are recorded by the Norwegian Medicinal Depot AS, a state-owned drug wholesaler,
on behalf of the Directorate of Health. Such data were
obtained from the Norwegian Medicinal Depot AS for the
purpose of this study.
In Norway, the Anatomical Therapeutic Chemical
(ATC) classification system is used to classify human
medicinal products and the ATC veterinary (ATCvet)
classification is used for veterinary medicinal products.8,9
These systems were used in this study. All approved human
and veterinary antibacterial specialities belonging to the
following ATC/ATCvet (Q) groups were included in
the study: gastrointestinal infections (A07AA/QA07AA),
uterine infections (G04AA AB AC/QG01AA AE),
and antibacterial drugs for systemic use (J01–J04/QJ),
including intramammary dose applicators (QJ51). In Norway, a selection of medicated feeds for farmed fish are
approved by the drug authorities for therapeutic use only
and are classified as pharmaceutical specialities. These
products are included in the QJ group. Additionally, this
study included a raw material product containing 20%
oxytetracycline (oral powder) which is used in pigs, and an
ex tempore product containing 50% phenoxymethylpenicillin (po powder) which is used in poultry. Both these
products are prescribed for therapeutic use only. Additionally, human and veterinary antibacterial drugs sold on
exemption from marketing authorization and stocked on a
regular basis by the wholesalers were also included. The
data for these preparations were calculated only for 1996.
Dermatological, eye and ear preparations were not
included in this study.
The amount of active substance, in kilograms, was
chosen as the unit of measurement. The amounts, in kilograms of active substance, of human and veterinary
antibacterial agents supplied by wholesalers to pharmacies
and hospitals, and by feed mills, were calculated from sales
figures. The data for benzyl penicillin salts and esters
(procaine penicillin and penethamate hydriodide) were
converted to the corresponding values for benzyl penicillin.10,11
In order to estimate the potential of selection pressure
due to oral use of antibacterial drugs in humans and
animals, the data were split according to the route of
administration. Data on the size of the human and livestock
populations, and of the total biomass (tonnes) of farmed
fish ‘at risk’ in 1992 and 1996, were obtained from the
Norwegian Statistical Yearbooks 199312 and 199713 while
data on pigs and poultry were obtained from R. Bruholt
(personal communication). For farmed fish, the data are
expressed as amounts, in tonnes, sold.
In Norway, a limited number of antibacterial feed
additives are licensed for growth-promoting purposes in
244
Consumption of antibacterial drugs in Norway
poultry, and sales figures of these substances are included
in this study. Anticoccidial drugs (coccidiostats) authorized
as feed additives and which also possess antibacterial activity (ionophore antibiotics) are also included in the study,
even though these substances are not classified as antibacterials within the European Union (Council Directive
70/524/EEC). Sales data for these products are presented
in this paper to give a picture of the overall selective pressure exerted by antibacterial drug use in Norway. Ionophore antibacterial drugs are not used in human medicine.
Annual sales figures for feed additives, in kilograms of
active substances according to target animal, were obtained
from the Norwegian Agricultural Inspection Service.14
Results
During the study period, there was a total reduction of 37%
in the overall use of antibacterial drugs in Norway (Table
I). Therapeutic use in domestic animals and farmed fish
declined by 76% from 1992 to 1996. While overall use in
domestic animals and farmed fish, both as therapeutics and
as feed additives with antibacterial effects, declined by
67% from 1992 to 1996, use in human medicine was almost
constant, a slight increase of 0.6% being recorded. The
sales, in 1996, of human and veterinary antibacterial drugs
not licensed on the Norwegian market contributed only 67
kg and 32 kg active substances, respectively. These figures
are not included in following presentation.
Sales of antibacterial veterinary drugs for therapeutic
use in domestic animals declined by 17% from 1992 to 1996
(Table I). The overall use in domestic animals of antibacterial drugs for therapeutic use and as feed additives fell
by 13%, while the amount of antibacterial drugs sold for
treatment of bacterial infections in farmed fish fell by 96%.
The use of antibiotic feed additives declined by 95%, while
the use of ionophore coccidiostats increased by 22% (Table
II).
The use of penicillins for the treatment of domestic
animals increased from 31% of the total therapeutic use in
Table I. Sales (in kilograms of active substance) in
Norway of approved antibacterial drugs for therapeutic
use and feed additives (antibacterial growth-promoters
and coccidiostats with antibacterial effects)
Antibiotic use
1992
1996
Human medicine
Veterinary medicine
domestic animals
fish farming
Feed additives
Total
34,496
34,694
9756
27,485
5218
76,955
8091
1037
4970
48,792
1992 to 38% in 1996, while the corresponding use of aminoglycosides (dihydrostreptomycin) constituted 31% in 1992
and 24% in 1996 (Table III). -Lactamase-sensitive penicillins were the predominant penicillins used in domestic
animals in both 1992 (98%) and 1996 (96%). The contribution of tetracyclines to drug use in domestic animals fell
from 7.7% in 1992 to 4.3% in 1996.
In human medicine, consumption of penicillins represented 54% and 57% of the total annual use of antibacterial
drugs in 1992 and 1996, respectively. -Lactamase-sensitive
penicillins were the most extensively prescribed penicillin
group in human medicine in both 1992 (86%) and 1996
(84%). Human medicine contributed 45% to the total
amount of antibacterial drugs used in Norway in 1992; the
corresponding figure for 1996 was higher, 71% (Figure 1).
Overall use in Norway of quinolones and tetracyclines
declined by 92% and 68%, respectively, from 1992 to 1996.
The contributions to the total use of quinolones and tetracyclines of preparations approved for use in human and
veterinary medicine (domestic animals and farmed fish)
respectively, in 1992 and 1996, are presented in Figure 2.
Total human and livestock populations, and biomass
(tonnes) of farmed fish in 1992 and 1996 in Norway, ‘at risk’
of possibly being treated with antibacterial drugs, are
presented in Table IV.
As regards route of administration, the proportion of
antibacterial therapeutics administered as injectable drugs
in domestic animals was 53% and 52% in 1992 and 1996
respectively, while oral administration accounted for 33%
in both years, when measured as kilograms of active substance (Table V). Oral administration through the feed is
the sole route used for systemic antibacterial drug treatment in farmed fish. Of the overall consumption of antibacterial drugs in domestic animals, both as therapeutics and
as feed additives, oral formulations comprised 56% in 1992
and 58% in 1996 (kilograms of active substance).
Table II. Sales (in kilograms of active substance) in
Norway of feed additives with antibacterial effects
(antibiotics and ionophore coccidiostats) according to
target animal (Norwegian Agricultural Inspection
Service, 1997)
Feed additives
Antibiotics
avoparcin
zinc bacitracin
total
Coccidiostats
lasalocid
monensin
salinomycin
narasin
total
245
Target animal
1992
1996
chicken/turkey
hens/turkey
779
408
1187
0
64
64
chicken/turkey
chicken/turkey
chicken
chicken
1557
1516
958
0
4031
480
891
27
3508
4906
K. Grave et al.
Table III. Sales (in kilograms of active substance) in Norway, in 1992 and 1996, of antibacterial drugs
for therapeutic use in human medicine (H), domestic animals (A) and farmed fish (F) according to
class of drug (ATC/ATCvet classification). Data were obtained from Norwegian wholesalers
1992
Class of drugs
H
A
Aminoglycosides
Amphenicols
Carbapenems
Cephalosporins and related agents
Glycopeptides
Hydrazide derivatives
Imidazoles
Lincosamides
Macrolides
Methenamine products
Monobactams
Nitrofurans
Penicillins
-lactamase sensitive
-lactamase resistant
extended spectrum
Pleuromutilins
Polyene antibiotics
Polymyxins
Quinolones
Rifamycins
Steroid antibacterials
Sulphonamides
Tetracyclines
Trimethoprim and derivatives
Total
20
105
21
1428
15
42
246
106
2783
3497
6
134
3037
4
0
0
0
0
0
42
35
0
0
0
15,940
478
2065
0
51
0,1
367
56
6
2750
3185
1193
34,496
2932
0
47
182
0
0
1
0
0
2581
752
144
9756
In human medicine, consumption of peroral antibacterial drugs constituted 92% and 91%, of total sales in
1992 and 1996, respectively. The corresponding figures for
injectable antibacterial drugs were 7% and 8%. Of the
injectable drugs, the -lactamase-sensitive penicillins made
the major contribution, both in humans (Table VI) and in
domestic animals (Table V).
The number of antibacterial substances approved for
human and veterinary use on the Norwegian market
increased from 1992 to 1996 by 11% and 22%, respectively
(Table VII). Only one new substance (florfenicol) was
approved for use in farmed fish over the same period.
Discussion
The sales figures of antibacterial drugs for therapeutic use
presented in this study are based on annual statistics on
drugs sold by Norwegian wholesalers to pharmacies and
1996
F
H
A
F
0
0
0
0
0
0
0
0
0
0
0
0
21
50
25
1761
19
0
297
212
2385
4581
5
124
1932
0
0
0
0
0
0
45
18
0
0
0
0
64
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
17,520
0
0
4872
4113
980
27,485
16,732
670
2463
0
84
1
431
37
7
1677
2191
921
34,694
2956
5
123
233
0
0
18
0
0
2235
351
176
8091
0
0
0
0
0
0
946
0
0
0
27
0
1037
hospitals. Because pharmacies only stock drugs on a short
term basis (Haug, K., unpublished data), the wholesalers’
figures roughly correspond to the actual amounts of the
drugs prescribed during the study period. The feed mills
report sales of antibacterial drugs for therapeutic use in
farmed fish to the Norwegian Medicinal Depot AS. These
figures reflect the actual prescribing patterns because the
feed mills dispense medicated feed directly to the fish farmers only on veterinary prescription. Antibacterial feed
additives are sold directly to the farmers, so the data give a
rough picture of the use of these substances. Drugs which
are for use in humans and which are also prescribed and
sold for use in animals cannot be differentiated and are
therefore recorded as sold for human use and included as
such in the overall sales data.
Methenamine products for human use and ionophore
coccidiostats constitute two important groups of antibacterial agents not usually included in studies on overall use
of antibacterial drugs. They were, however, included in the
246
Consumption of antibacterial drugs in Norway
Table IV. Total human and livestock (main species)
populations, and biomass (tonnes) of farmed fish in 1992
and 1996 in Norway, ‘at risk’ of possibly being treated with
antibacterial drugs (Norwegian Statistical Yearbook,
1993; 1997; Statistics Norway, unpublished dataa)
Population
Human
Cattle
Sheep ( 1 year old)
Dairy goats
Breeding pigsa
Slaughter pigsa
Hensa
Slaughter chickens (broilers)a
Atlantic salmon
Rainbow trout
Figure 1. Distribution of total sales in 1992 and 1996 of antibacterial drugs approved for use in humans ( ), in domestic
animals ( ), in farmed fish ( ) and as feed additives ( ).
Figure 2. Contributions to total sales in 1992 and 1996 of
quinolones and tetracyclines approved for use in human ( ) and
in veterinary medicine (domestic animals and farmed fish ( )).
present study as they may exert a selective pressure on the
bacterial flora. In conclusion, the sales figures presented in
this study are considered to represent the overall use of
antibacterial drugs in Norway in 1992 and 1996.
There are several limitations to the use of weight as a
comparator for antibiotic consumption and its impact on
the development of resistance. Several other factors are
also important, such as antibacterial potency, spectrum of
activity, mode of action and the number of macro- and
microorganisms involved. Moreover, factors such as the
1992
1996
4,273,634
981,300
1,083,100
61,700
93,100
1,214,700
3,714,200
16,850,642
124,138
6582
4,369,957
1,005,800
1,032,300
57,900
92,500
1,328,500
3,460,600
23,264,300
301,426
22,267
number of species exposed to the drug and the fate of the
drug in the body of the target species and in the environment are also important. Sales figures, expressed in kilograms of active substance, should therefore be interpreted
with care and at least each substance group should be
assessed for trends. The rationale of this approach would
be to get closer to a relevant measure of selective pressure
on antibacterial resistance.
To avoid some of the drawbacks of using the kilogram as
the unit of measurement, the concept of DDD has been
developed for application in studies in human medicine;8
population number or hospital days is used as the denominator when comparing drug use. DDD can also be used
indirectly to estimate the number of individuals treated,
this figure being derived by dividing DDD by the average
duration of treatment, if known. DDD can be applied to
compare human antibiotic consumption between institutions and between countries, though as yet only a few countries publish statistics on DDD. In the Nordic countries,
DDD statistics in human medicine have been published
since the beginning of 1970. The overall human consumption of antibacterial drugs in Norway amounted to 15.1
DDD/1000 inhabitants/year in 1992 and decreased to 14.5
DDD in 1996.5 Finland, Iceland and Sweden have a higher
human consumption of antibacterial drugs than Norway. 15
Because the figures published from Denmark do not
include use in hospitals, as do the figures from the other
Nordic countries, the Danish figures are not comparable
with consumption in other Nordic countries.15
DDD cannot be employed to compare antibiotic consumption in human and veterinary medicine as it is possible
to calculate such data for only a few veterinary drugs. The
only parameter for which data are generally available, so
far, is the amount used, in kilograms of active substance.
The present study revealed that in Norway, overall sales of
247
K. Grave et al.
Table V. Sales (in kilograms of active substance) in Norway in 1992 and 1996 of antibacterial drugs for
therapeutic use in domestic animals (excluding farmed fish). Data were obtained from Norwegian wholesalers
1992
Class of drugs
iu
inj
Aminoglycosides
Amphenicols
Imidazoles
Lincosamides
Macrolides
Penicillins
-lactamase sensitive
-lactamase resistant
extended spectrum
Pleuromutilins
Quinolones
Sulphonamides
Tetracyclines
Trimethoprim and derivatives
Total
38
0
0
0
0
1925
0
0
0
0
11
0
0
0
0
303
5
0
357
2579
0
41
9
1
350
239
51
5195
1996
imam
po
iu
inj
imam
po
644
4
0
0
0
430
0
0
42
35
33
0
0
0
0
1063
0
0
0
14
562
0
0
0
0
273
0
0
45
5
342
0
0
0
0
0
17
0
1007
0
0
6
172
0.1
1927
491
93
3197
10
0
0
0
0
265
4
0
312
2572
0
58
11
14
254
151
51
4187
374
5
2
0
0
0
11
0
953
1
0
62
221
4
1716
185
125
2639
Abbreviations: iu, intrauterine; inj, injectable; imam, intramammary; po, oral.
antibacterial drugs, including feed additives with antibacterial effects for use in domestic animals, decreased by 37%
during the period 1992–1996, from 76,955 kg to 48,792 kg.
This reduction was entirely due to a fall in the consumption
of veterinary medicines, particularly those used in fish
farming, whereas amounts used in humans remained
unchanged. The decline in the use of antibacterial drugs in
domestic animals, especially in farmed fish, has been due to
several factors, the most important of which are discussed
below.
Because of the increasing attention being focused on
antibacterial drug resistance, Norwegian livestock farming
organizations initiated a campaign aiming to reduce the use
of antibacterial drugs (in kilograms of active substance) by
25% over a 5 year period (1996–2000), 1995 being chosen
as the reference year. As drugs used to treat bovine
mastitis make up a substantial proportion of the antibacterial drugs used in veterinary medicine, comprehensive
guidelines on drug therapy in mastitis were published to
support this campaign.16 These guidelines are intended to
serve as a basis for rational drug therapy in bovine mastitis,
the aim being to reduce the use of antibacterial drugs in
this connection. Several conferences and meetings were
arranged to follow up both the campaign and the guidelines, focusing on the desirability of increasing the relative
use of penicillin, with a corresponding reduction in the
prescribing of benzyl penicillin and dihydrostreptomycin
combinations and of tetracyclines.
During the period 1992–1996, the therapeutic use of
antibacterial drugs in traditional veterinary medicine
declined by 17%, the main part of this reduction occurring
in 1996, when use was reduced by 14% compared with
1995.17 It is important to note that the size of the livestock
population ‘at risk’ remained almost constant, the increase
which took place from 1995 to 1996 being very slight. The
reported annual frequencies of bacterial diseases in food
animals were the same in 1996 as in 1995. The reduction in
the use of antibacterial drugs in domestic animals can
therefore be attributed almost solely to changes in veterinary prescribing patterns, due to more prudent drug use
and the application of better diagnostic criteria. An important contribution to the general decline in the use of
antibacterial drugs in domestic animals comes from the
reduced frequency with which antibacterial drug therapy is
employed in cases of chronic mastitis in cattle (Mørk, T.,
personal communication).
Another important change in veterinary prescribing
behaviour found in the present study was the relative
increase in the prescribing of penicillins, with a corresponding decrease in the amount of aminoglycosides and
tetracyclines prescribed for use in domestic animals. The
fall in consumption of aminoglycosides was due to less frequent prescribing of combined preparations of benzyl penicillin and dihydrostreptomycin.17 It is concluded that the
campaign initiated by the Norwegian livestock farming
organizations seems to have been very successful so far.
Of the sulphonamides sold for use in domestic animals,
sulphamethoxypyridazine contributed 1409 kg and 1088 kg
in 1992 and 1996, respectively (Grave, G., unpublished
data).17 The main indication for this drug is the treatment
248
Consumption of antibacterial drugs in Norway
Table VI. Sales (in kilograms of active substance) in Norway in 1992 and 1996 of antibacterial
drugs for therapeutic use in humans. Data were obtained from Norwegian wholesalers
1992
1996
Class of drug
ivag
inj
po
Aminoglycosidesa
Amphenicols
Carbapenems
Cephalosporins and related agents
Glycopeptides
Hydrazide derivatives
Imidazoles
Lincosamides
Macrolides
Methenamine products
Monobactams
Nitrofurans
Penicillins
-lactamase sensitive
-lactamase resistant
extended spectrum
Polyene antibiotics
Polymyxins
Quinolones
Rifamycins
Steroid antibacterials
Sulphonamides
Tetracyclines
Trimethoprim
Total
0
0
0
0
0
0
133
0
0
0
0
0
20
67
21
711
13
0
112
15
12
0
6
0
0
38
0
717
3
42
0
91
2771
3497
0
134
1014
14,926
141
337
340
1725
0
51
0.1
0
0
367
0
56
1
5
17
2733
6
3180
3
1139
2501
31,861
0
0
0
0
0
0
0
0
0
0
0
133
ivag
inj
po
0
0
0
0
0
0
169
13
0
0
0
0
21
14
25
956
16
0
127
31
14
0
5
0
0
36
0
805
3
0
0
168
2371
4581
0
124
0
0
0
0
0
0
0
0
0
0
0
182
1093
189
283
0
1
7
0
1
14
5
3
2805
15,639
480
2180
84
0
425
37
6
1663
2187
918
31,706
Abbreviations: ivag, intravaginal; inj, injectable; po, oral.
Additionally, 0.09 kg of gentamicin formulated for implantation in connection with surgery, was sold in each year.
a
Table VII. The number of active substances and antibacterial pharmaceutical preparations
approved for the Norwegian market in 1992 and 1996
Preparations for humans
No. of substances
No. of preparations
Preparations for domestic animals
1992
1996
1992
1996
54
436
60
490
18
124
22
155
of mastitis of sheep. Based on estimated frequencies of
mastitis in sheep and the recommended treatment dose,
it can be estimated that most of the sulphamethoxypyridazine sold is indeed used for treatment of mastitis
in sheep. Pharmacokinetic studies and studies on the
inhibitory effects of sulphamethoxypyridazine, however,
indicate that the clinical efficacy of this form of therapy of
mastitis in sheep is uncertain.18,19 The implication is that
there is potential for further reduction in the use of antibacterial drugs in domestic animals in Norway.
The rapid expansion of the Norwegian fish farming
industry was accompanied by recurrent problems with bacterial infectious diseases. This in turn led to the periodic use
of large amounts of antibacterial drugs in the 1980s and the
beginning of the 1990s.6 In 1989, furunculosis became
endemic in several parts of Norway for the first time and
249
K. Grave et al.
caused severe losses. However, from 1992 to 1994, the use
of antibacterial drugs in farmed fish decreased from 27,485
kg to 6144 kg active substance and since 1994, annual consumption has remained fairly constant, at around 1 tonne.6
During this period, sales of farmed fish increased by
100%. It has been shown that the introduction of oiladjuvanted vaccines against furuncolosis in 1992 was the
single most important factor contributing to the substantial
reduction in the use of antibacterial drugs in fish farming in
Norway since 1992.20 The overall reduction in Norway in
the use of quinolones (92%) and of tetracyclines (68%) in
the study period has almost solely been due to the use of
oil-adjuvanted vaccines in furunculosis.
The use of the antibacterial feed additives avoparcin and
zinc bacitracin declined by 95% from 1992 to 1996. An
important reason for this was that avoparcin was prohibited in Norway for use as a growth promoter from 31 May
1995, because an association between the use of avoparcin
and the prevalence of vancomycin-resistant entrococci was
reported.21–23 Moreover, the Norwegian pig and poultry
industry has voluntarily agreed not to use antibacterial feed
additives, apart from ionophores; as a consequence the use
of zinc bacitracin is now slight. When avoparcin was withdrawn from the market in Norway, narasin was authorized
as a feed additive as an alternative agent to prevent
necrotic enteritis in chicken. In consequence of the withdrawal of avoparcin, the use of ionophore feed additives
increased substantially (22%) during the study period. The
overall use of feed additives (in kilograms of active substance) with antibacterial effect nevertheless declined by
5%. This also contributed to the overall reduction of 67%
in the use of antibacterial drugs in domestic animals and
farmed fish which took place in Norway from 1992 to 1996.
The few studies so far published on overall antibacterial
drug use in veterinary medicine in other countries are
mainly from Sweden.24–26 In only one of these studies26 was
the methodology used to study the consumption of antibacterial drugs for therapeutic purposes in domestic animals
the same as in the present study. The Swedish study26
showed that sales of antibacterial drugs used for therapeutic purposes in domestic animals in Sweden fell from
23,207 kg active substance in 1992 to 18,521 kg in 1996, a
reduction of 20%, which was similar to the 17% reduction
in Norway during the same period.
The Swedish data on the consumption of feed additives
with antibacterial effect are not fully comparable with the
data from the present study. However, as in Norway, the
use of ionophores in Sweden has increased slightly in the
1990s, while the number of animals ‘at risk’ in both countries has remained almost constant from 1992 to 1996.26 It
can therefore be concluded that the overall use, in kilograms of active substances, of antibacterial drugs in domestic animals has declined from 1992 to 1996 both in Norway
and Sweden.
In Denmark, the consumption of antimicrobial drugs in
animals has been estimated as part of the Danish Inte-
grated Antimicrobial Resistance Monitoring and Research
Programme.27 The therapeutic use of antibacterial drugs in
Denmark in 1995 was estimated to be 49.6 tonnes of active
substance, while the total sales of antibacterial feed additives amounted to 93.9 tonnes of active substance.27 The
estimated use, of antibacterial drugs for therapeutic
purposes, in the Netherlands in 1990 was 300 tonnes of
active substance, and as feed additives 300 tonnes.28 The
corresponding figures for the USA in 1985 were 1100
tonnes and 7000 tonnes, respectively.29 Publications or
reports from Denmark, the Netherlands, USA and other
countries presenting data on consumption of antibacterial
drugs in humans or animals do not give the data source,
inclusion criteria, or the classification system used. Nor are
data about number of animals ‘at risk’ of being treated with
an antibacterial drug presented in these studies.27–29 It is
therefore difficult to compare the data with those from the
present study.
All antibacterial drugs for veterinary therapeutic use in
Norway are on prescription only, have to be dispensed
through pharmacies, and are classified according to the
ATCvet classification system. This makes it easy to collect
valid and comparable data on the consumption of veterinary antibacterial agents, and thus to survey overall use
and trends in prescribing patterns. This distribution system
for veterinary drugs is identical to those existing in other
Nordic countries. The fact that veterinary drugs for therapeutic use are distributed through pharmacies, both to animal owners and for direct use by veterinarians, implies that
there are no economic incentives to prescribe antibacterial
drugs. This is different from the situation in most European
countries.30 Moreover, in Norway promotional activities by
the drug companies directed at the veterinarians is thought
to be negligible compared with the situation in countries
where pharmaceutical companies are allowed to sell drugs
directly to veterinarians. Drug prices are set by the Norwegian drug authorities and the drug companies are not
allowed to offer discounts directly to veterinarians in order
to influence the prescribing patterns. Although comparable
studies are lacking, there is reason to believe that both the
absolute and relative use of antibacterial therapeuticals in
domestic animals in Norway are low compared with those
in most other European countries. Nevertheless, there is
probably still a significant potential for reducing antibacterial drug use in human medicine, and also for a further
reduction in veterinary use in Norway.
The modest use of antibacterial drugs in human and
veterinary medicine in Norway may be explained by the
strict policy which has been implemented concerning the
approval of new drugs. Until 1 January 1994, Norwegian
drug legislation included the so-called ‘need’ clause, which
allowed the approval of new drugs only if they could be
shown to have significant advantages over drugs already
registered in Norway. In this context, the potential for the
development of drug resistance was one of the criteria
taken into account.
250
Consumption of antibacterial drugs in Norway
As a consequence of the European Economic Area
agreement (between the EU and EFTA countries), Norway had to revoke the ‘need’ clause from 1 January 1994.
The present study showed that there was an increase in the
number of new substances and preparations approved for
use both in human and veterinary medicine in Norway
during the study period. Nevertheless, the use of antibacterial drugs in animals decreased over the same period,
while use in humans remained constant from 1992 to 1996.
As far as we know, little data has been published comparing the use of antibacterial drugs in humans and animals
on a national basis. In the USA, it has been estimated that
about half, by weight, of the antibiotics sold are used in
livestock farming with almost 90% of agricultural use being
for prophylaxis or growth promotion rather than for treatment of diseased animals.29
In both human and veterinary medicine, criteria for
antibiotic use should include the use of such drugs only
when they are clinically indicated, and the selection of the
appropriate agent, dose and duration of therapy. In addition, antibacterial drugs used in veterinary medicine should
not exert selection pressure with regard to the development by bacteria of antibiotic resistance to drugs used in
humans. With these principles in mind, reservations could
be raised against current veterinary prescribing patterns
for three classes of antibiotics in Norway: aminoglycosides,
quinolones and sulphonamides. Veterinary use (amount)
in Norway in 1996 accounted for 99%, 69% and 57%,
respectively, of total consumption of these classes of drugs.
The sales in 1996 of tetracyclines in human medicine represented 85% of the overall therapeutic use of this group of
drugs in Norway, while 87% of the total amounts of penicillins was for human use.
Although published data on antibacterial drug use are
available for only a few other countries, there is reason to
believe that the situation with regard both to the amounts
used and the therapeutic profile of antibacterial drug use in
human medicine in Norway compares favourably with that
in most other industrialized countries. This study showed
that, in Norway, narrow spectrum -lactamase-sensitive
penicillins accounted for 48%, and the penicillin group as a
whole for 57% of total human consumption. Consumption
of cephalosporins (5.1% of overall human use) is fairly
modest, but increased by 23% from 1992 to 1996. The use
of quinolones in human medicine is also modest, representing 1.2% of total human use in 1996. Of the tetracyclines,
only oxytetracycline is used in domestic animals and
farmed fish in Norway. The proportion of the sales in
human medicine of each tetracycline substance remained
almost constant during the study period. It is thus concluded that there has really been a reduction in the use of
tetracyclines in Norway.
The extent of selection of resistant bacterial strains
depends of a number of factors, including type of antibacterial drug, the way it is used (route of administration, dose
and duration) and the number of bacteria exposed to the
antibacterial drug in question.26 The present study has
shown that, in Norway, oral use of antibacterial drugs
(including feed additives and ionophores) represented
58% of the total consumption in livestock in 1996, the
corresponding figure being 92% in human medicine. As the
intestine contains a large number of various bacterial
species, it is suggested26 that oral administration of antibacterial drugs may result in the development of a higher
proportion of resistant bacterial strains than parenteral
administration and that the intestine then may act as reservoir for resistant bacteria. In the risk assessment of antibacterial drug resistance, splitting the data into oral and
injectable use may thus be important. However, this
hypothesis needs further investigation, including studies on
the impact of different routes of administration on antibacterial drug resistance and therapeutic outcome.
It is important that comparable data on the consumption
of antibacterial drugs in humans, animals and farmed fish in
different countries be obtained in the future, not only
to evaluate the impact of antibiotic policies, but also to
estimate the selective pressure and to look for possible
correlations between the use of specific groups of antibiotics and the emergence of resistance. If antibacterial
drug consumption data are to be reliable and comparable,
they will have to be gathered according to strict methodological standards, of which the most essential continue to
be the use of a common drug classification system and of an
internationally agreed unit of measurement.8,31
Acknowledgement
This work was supported in part by a grant from the
Research Council of Norway.
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Received 23 February 1998; returned 27 April 1998; revised 19 May
1998; accepted 7 September 1998
252