Presentation from the 3rd Joint Meeting of the Antimicrobial Resistance and Healthcare-Associated Infections (ARHAI) Networks, organised by the European Centre of Disease Prevention and Control - Stockholm, 11-13 February 2015

1. An agency of the European Union
Consumption of antimicrobials for
humans and food-producing
animals (from JIACRA
report)/Establishing DDDAs and
DCDAs animals
3rd Joint Meeting of the Antimicrobial Resistance and Healthcare-Associated Infections
(ARHAI) Networks. Stockholm, 11-13 February 2015
Presenter: Kari Grave
Developed by Zoltan Kunsagi, Kari Grave and Jordi Torren Edo
European Medicines Agency / Veterinary Medicines Division

2. Outline
• Comparison consumption antimicrobials humans animals
• Material and methodology
• Results – overall and by antimicrobial classes
• Discussion on results
• Establishment of DDDAs and DCDAs
• State of play
• Harmonization human medicine on principles for assignment of
DDDAs
• Concluding remarks
1

3. 2
Joint Interagency Antimicrobial Consumption and
Resistance Analysis (JIACRA) Report
ECDC/EFSA/EMA first joint report on the integrated analysis of the
consumption of antimicrobial agents and occurrence of antimicrobial
resistanse

4. Reporting consumption in humans by numbers of DDD per 1 000
inhabitants per day and by milligrams per kilogram estimated
biomass
Consumption of AMs
•In humans: DDD per 1000 inhabitants per day (ESAC-Net)
•In animals: milligrams per PCU (ESVAC)
To facilitate comparisons between human and veterinary medicine, data
from ESAC-Net were converted into milligrams per kilogram estimated
biomass humans. This approach is supported by an analysis on data
reported as total DDD per 1 000 inhabitants per day and total milligrams
of active substance per kilogram estimated biomass (see next slide)
3

5. Scatter plot of consumption in humans reported as total DDD per 1 000
inhabitants per day and total milligrams of active substance per kilogram
estimated biomass for the 26 countries included (data for 2012)
4
The scatter plot shows a
significant correlation
between two measures
Spearman’s rank
correlation coefficient
rho = 0.87; P<0.0001

6. Total tonnes of active substance sold and estimated
biomass in 26 EU/EEA countries applied for the
analyses
• In 2012, 3 400 and 7 982 tonnes of active substance of antimicrobials
were sold for use in humans and food-producing animals,
respectively, in the 26 EU/EEA countries.
• The estimated biomass, expressed as 1000-tonnes, was 28 884 for
humans and 55 421 for animals.
5

7. Comparison of biomass-corrected consumption of antimicrobials
(milligrams per kilogram estimated biomass) in humans and
animals by country in 26 EU/EEA countries in 2012
6

8. Overall consumption
• In 2012 the average consumption expressed in mg per kg of
estimated biomass was 116.4 mg/kg in humans (range: 56.7 –
175.8 mg/kg) and 144.0 mg/kg in animals (range: 3.8 – 396.5
mg/kg).
• Consumption in food-producing animals was lower or much lower than
in humans in 15 of 26 countries, in three countries they were similar,
and in eight countries consumption in food-producing animals was
higher or much higher than in humans.
• Overall consumption of antimicrobials (population weighted mean)
was higher for animals than for humans.
7

9. Biomass-corrected consumption of 3rd- and 4th-generation
cephalosporins for humans and food-producing animals by country in 26
EU/EEA countries in 2012
8
Asterisk (*) denotes that only community consumption data were available for human medicine. Figures of human sales from these countries probably represent a
considerable underestimate.
The consumption of 3rd- and 4th-
generation cephalosporins was
much lower for animals than for
humans.
This antimicrobial class is
predominantly used in hospitals,
and therefore the comparison may
be misleading for countries not
reporting (*) such hospital
consumption.

10. Population corrected consumption of fluoroquinolones for humans and
food-producing animals by country in 26 EU/EEA countries in 2012
9
Asterisk (*) denotes that only community consumption data were available for human medicine.

11. Discussion on results
Limitations hamper the comparison of consumption of antimicrobials for
humans and food-producing animals. An agreed and comparable unit
of measurement is needed. More data are needed on an animal
species level.
Nevertheless, the presented data illustrate that there are wide variations
between countries both in the overall consumption figures and for the
consumption of the 3rd- and 4th-generation cephalosporins and
fluoroquinolones.
10

12. Establishment of DDDAs (and DCDAs) by ESVAC
• Assisted by ad hoc working group on technical units of
measurements: Gérard Moulin (chair), Christina Greko, Erik
Jacobsen, Inge van Geijlswijk, Cedric Müntener and Irene
Litleskare
• Data on daily dose and number of days of treatment obtained
from Summary of Products Characteristics (SPCs) for
antimicrobial veterinary medicinal products provided for
broilers, cattle and pigs by nine EU-countries : CZ, DE, DK, FI,
FR, NL, SE, SP and UK.
11

13. Establishment of DDDAs (and DCDAs) – state
of play
• Principles for assignment of DDDA and DCDA under
development
• Published for consultation end of February with a consultation time
of 2 months
• Revised principles applied for the assignment of DDDAs and
DCDAs
• As a first step DDDAs will be assigned
12

14. Principles for assignment DDDAs (and DCDAs)
• Aim to harmonize principles with human medicine
• Dissimilarities human/ veterinary medicine
– Human medicine: DDD established for the purpose of drug
consumption studies and mainly in order to follow
therapeutic trends
– Veterinary medicine: Therapeutic trends but AMR main aim
13

15. 14
Harmonization with human medicine -
challenges/differences cont.
Differences – how antimicrobials are used
Meat production - group/herd treatment (oral); some use of injections
Dairy cows - local treatment for mastitis; some use of injections
Group/herd
treatment; oral
treatment main
route; some use of
injections
Group/herd
treatment
– oral
treatment
only
14

16. DDD – combinations human medicine
The DDDs assigned for combination products are based on the
main principle of counting the combination as one daily dose,
regardless of the number of active ingredients included in the
combination: “If a treatment schedule for a patient includes e.g.
two single ingredient products, then the consumption will be
measured by counting the DDDs of each single ingredient product
separately”
The numbers of combination antimicrobials products in human
medicines consists mainly of sulfonamide-trimethoprim
combinations (synergism) and antibiotics combined with an
enzyme inhibitor.
15

17. Sales (tonnes) of oral powders, oral solution and
premixes sold as single and combination antimicrobial
VMP by country
16
For some
countries the
proportion of
combination
antimicrobial
VMPs is
relatively
high –
important to
measure all
ingredient.
For 26
countries it
represents
14% of the
sales

18. Example reporting single and combination VMPs
Pack
size Strength No sold mg used
# DDDA
(mg/kg)
# DCDA
(mg/kg)
Prod 1 Oxytetracycline 1000 g 70 mg/g 100 7000000 233 47
Prod 2 Colistin 1000 g 20 mg/g 100 2000000 400 80
Prod 3 Colistin 1000 g 12 mg/g 100 1000000 240 48
Oxytetracycline 1000 g 70 mg/g 100 7000000 233 47
17
Calculated numbers (#) of DDDAs and DCDAs, in thousands, of three different
products (oral powder) consumed by pigs. Preliminary DDDAs and DCDAs used
In case the 2nd
ingredient for product 3
is not included in the
analysis only half of the
consumption (selection
pressure) of
oxytetracycline would
have been identified
0
10
20
30
40
50
60
70
80
90
Oxytetracycline
(P 1)
Colistin (P 2) Colistin (P 3) Oxytetracycline
(P3)
DDDA(1000)

19. Concluding remarks
• DDDA and DCDA will be assigned for broilers, cattle and pigs
• Principles on assignment to be harmonized with human
medicine. Exceptions will be for example assignment of DDDAs
for each ingredient in a combination VMP
• Long-acting injectables to be carefully addressed
• Which indicator to use for reporting of data in order to make it
comparable with the human data have to be further discussed
18

20. Acknowledgement
The representatives of the MSs and other members of the different
networks are thanked for providing data for the surveillance networks:
• ECDC: EARS-Net, ESAC-Net and FWD-Net;
• EFSA: Scientific Network for Zoonosis Monitoring Data;
• EMA: ESVAC
This joint report is based on data provided by the above-mentioned
networks and on the major contributions of the following experts:
• ECDC: Yvonne Agersø, Ole Heuer, Liselotte Diaz Högberg, Arno
Muller, Klaus Weist, ThereseWestrell and Dominique Monnet.
• EFSA: Pierre-Alexandre Beloeil, Ernesto Liebana-Criado, Rob van
Oosterom, Pascal Sanders,Christopher Teale and John Threlfall.
• EMA: Kari Grave, Christina Greko, Kristine Ignate, Zoltan Kunsagi,
Gérard Moulin (Chair) and Jordi Torren-Edo.
19

21. 20
Thank you for
your attention