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

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

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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

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)

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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)

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The scatter plot shows a

significant correlation

between two measures

Spearman’s rank

correlation coefficient

rho = 0.87; P<0.0001

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.

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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

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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.

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Biomass-corrected consumption of 3rd- and 4th-generation cephalosporins for humans and food-producing animals by country in 26 EU/EEA countries in 2012

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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.

Population corrected consumption of fluoroquinolones for humans and food-producing animals by country in 26 EU/EEA countries in 2012

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Asterisk (*) denotes that only community consumption data were available for human medicine.

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.

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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.

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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

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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

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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

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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.

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Sales (tonnes) of oral powders, oral solution and premixes sold as single and combination antimicrobial VMP by country

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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

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

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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 identified0

10

20

30

40

50

60

70

80

90

Oxytetracycline(P 1)

Colistin (P 2) Colistin (P 3) Oxytetracycline(P3)

DD

DA (

1000)

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

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AcknowledgementThe 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.

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Thank you for

your attention