antimicrobial use and antimicrobial resistance: chapter 6...
TRANSCRIPT
Antimicrobial use and Antimicrobial
resistance: chapter 6.7 and 6.8 of the OIE
Terrestrial Animal Health
Detailed presentation and implementation
Workshop for OIE national Focal Points for Veterinary
Products (2nd cycle) Vienna (Austria), 20-22 November 2012
Dr. Gérard Moulin
Anses/ANMV
OIE Collaborating Centre on Veterinary medicinal products (French agency for veterinary medicinal products / French Agency for Food,
Environmental and Occupational Health and Safety)
8 rue Claude Bourgelat - Parc d'activités de la Grande Marche - Javené - BP
90203 - 35302 Fougères – France
OIE International standards on antimicrobial resistance
Terrestrial Animal Health Code (2012) Section - 6: Veterinary Public Health
Chapter 6.7: Harmonisation of antimicrobial resistance surveillance and monitoring programmes (2003 - updated in 2012)
Chapter 6.8: Monitoring of the quantities and usage patterns of antimicrobial agents used in food producing animals (2003 - updated in 2012)
Chapter 6.9: Guidelines for the responsible and prudent use of antimicrobial agents in veterinary medicine (2003 - updated 2005)
Chapter 6.10: Risk assessment for antimicrobial resistance arising from the use of antimicrobials in animals (2004)
Manual of Diagnostic Tests and vaccines
for Terrestrial Animals
Chapter 4.1: Laboratory methodologies for bacterial
antimicrobial susceptibility testing (2003 - updated in 2012)
OIE International standards on antimicrobial resistance
Aquatic Animal Health Code (2012) Section - 6: Veterinary Public Health
Chapter 6.2: Introduction to the recommendations for controlling antimicrobial resistance (2011)
Chapter 6.3: Principles for responsible and prudent use of antimicrobial agents in aquatic animals (2011)
Chapter 6.4: Monitoring of the quantities and usage patterns of antimicrobial agents
used in aquatic animals (2012)
Chapter 6.5: Development and harmonisation of national antimicrobial resistance
surveillance and monitoring programmes for aquatic animals (2012)
Chapter 6.7: Harmonisation of antimicrobial
resistance surveillance and monitoring programmes
Chapter 6.7: Harmonisation of antimicrobial resistance surveillance and monitoring programmes
Content
• Objective / Purpose
• The development of antimicrobial resistance surveillance and
monitoring programmes
– 1. General aspects
– 2. Sampling strategies
– 3. Sample size
– 4. Sample sources
– 5. type of sample to be collected
– 6. Bacterial isolates
– 7. Storage of bacterial strains
– 8. Antimicrobial susceptibility testing
– 9. Recording, storage and interpretation of data
– 10. Reference laboratory and annual reports
Chapter 6.7: Harmonisation of antimicrobial resistance surveillance and monitoring programmes
Objective • To provides criteria for the development and harmonisation of antimicrobial
resistance surveillance and monitoring programmes
Purpose: why surveillance and monitoring are necessary?
NEW introduce the notions of active (targeted) and passive surveillance
encourage regional cooperation between members
1. To assess and determine the trends and sources of antimicrobial resistance
in bacteria
2. To detect the emergence of new antimicrobial resistance mechanism
3. To provide data for conducting risk analysis
4. To provide a basis for policy recommendations for animal and human health
5. To provide information for evaluating antimicrobial prescribing practices and for prudent use recommendations
Chapter 6.7: Harmonisation of antimicrobial resistance surveillance and monitoring programmes
General aspects:
• National AMR monitoring and surveillance programmes
should be scientifically based and may include the
following components:
a) statistically based surveys;
b) sampling and testing of food producing animals on the farm,
at live animal market or at slaughter;
c) an organised sentinel programme (targeted sampling of food
producing animals, herds, flocks and vectors;
d) analysis of veterinary practice and diagnostic laboratory
records.
Chapter 6.7: Harmonisation of antimicrobial resistance surveillance and monitoring programmes
Sampling strategy:
• Representativeness of the population, robustness of the method
• Criteria: sample source, animal species and category, health status,
sample selection, type of sample
Sample size:
Table 1. Sample size estimates for prevalence of antimicrobial resistance in a large population
90% Level of confidence 95% Level of confidence
Expected prevalence
Desired precision Desired precision
10% 5% 1% 10% 5% 1%
10% 24 97 2,429 35 138 3,445
20% 43 173 4,310 61 246 6,109
30% 57 227 5,650 81 323 8,003
40% 65 260 6,451 92 369 9,135
50% 68 270 6,718 96 384 9,512
60% 65 260 6,451 92 369 9,135
70% 57 227 5,650 81 323 8,003
80% 43 173 4,310 61 246 6,109
90% 24 97 2,429 35 138 3,445
Chapter 6.7: Harmonisation of antimicrobial resistance surveillance and monitoring programmes
Sampling sources:
• Examination of the livestock production system (Animal feed, Food
producing animals, Food)
Type of samples to be collected:
Table 2. Examples of sampling sources, sample types and monitoring outcomes
Source Sample type
Outcome
Additional information required or additional stratification
Herd or flock of origin
Faecal or bulk milk
Prevalence of resistant bacteria originating from animal populations (of different production types) Relationship resistance – antimicrobial use
Age categories, production types, etc. Antimicrobial use over time
Abattoir Faecal Prevalence of resistant bacteria originating from animals at slaughter
Caeca or intestine
As above
Carcass Hygiene, contamination during slaughter
Processing, packing
Food products
Hygiene, contamination during processing and handling
Point of sales (Retail)
Food products
Prevalence of resistant bacteria originating from food, exposure data for consumers
Various origins Animal feed Prevalence of resistant bacteria originating from animal feed, exposure data for animals
Chapter 6.7: Harmonisation of antimicrobial resistance surveillance and monitoring programmes
Which bacteria to monitor?
• Animal bacterial pathogens
• Zoonotic bacteria
– Salmonella
– Campylobacter
– Other emerging bacterial pathogens (MRSA, Listeria
monocytogenes…)
• Commensal bacteria
– Escherichia coli and enterococci
Chapter 6.7: Harmonisation of antimicrobial resistance surveillance and monitoring programmes
• Which antimicrobials to be used in susceptibility
testing?
– Reference to the OIE list of antimicrobials of veterinary
importance
• Recommendations on:
– Storage of bacterial strains
– Recording, storage and interpretation of data
– Reference laboratory and annual reports
• Need to designate a National Reference Centre
Examples: France, Europe
• Surveillance of bacterial pathogens (France)
Resapath:
http://www.resapath.anses.fr
• Surveillance of zoonotic and commensal
bacteria (Europe, EFSA)
http://www.efsa.europa.eu/en/efsajournal/doc/2597.pdf
Chapter 6.8:
Monitoring of the quantities and usage patterns
of antimicrobial agents used in food producing animals
Chapter 6.8: Monitoring of the quantities and usage patterns of antimicrobial agents used in food producing animals
Content
• Purpose
• Objectives
• Development and standardisation of
antimicrobial monitoring systems
– Sources of antimicrobial data
– Types end reporting formats of antimicrobial
use data
• Interpretation
Chapter 6.8: Monitoring of the quantities and usage patterns of antimicrobial agents used in food producing animals
Purpose:
• To describe an approach to the monitoring of
the quantities of antimicrobial agents used in
food producing animals
• In order to evaluate antimicrobial exposure,
need for quantitative information to monitor
usage patterns by animal species,
antimicrobial agents or class, type of use and
route of administration
Chapter 6.8: Monitoring of the quantities and usage patterns of antimicrobial agents used in food producing animals
Objectives:
This information is necessary:
- For interpreting antimicrobial resistance
surveillance data
- For risk management to evaluate the
effectiveness of efforts to ensure responsible
prudent use and mitigation strategies
- For risk communication purposes
Chapter 6.8: Monitoring of the quantities and usage patterns of antimicrobial agents used in food producing animals
• customs, import and export data,
• manufacturing and sales data
• Veterinary medicinal products registration
authorities,
• wholesalers, retailers,
• pharmacists, veterinarians, feed stores,
• feed mills
• Pharmaceutical industry associations
• veterinarians
• food animal producers
• Non conventional (internet sales …)
Basic sources
Direct sources
End-use sources
Data sources: sources of data will vary from country to country
Other sources
Chapter 6.8: Monitoring of the quantities and usage patterns of antimicrobial agents used in food producing animals
Type of antimicrobial use data:
- Weight in kilograms of the active ingredient per year
- Number of food producing animals by species, type of
production and their weight in kilograms for food
production per year
- Information on dosage regimen and route of
administration
Reporting formats of antimicrobial use data:
- Organised by species, route of administration and type
of use
Example: French Antimicrobial Sales/Use Monitoring system
• Started in 1999
– In accordance with OIE guideline
– agreement Industry ANMV/AFSSA
sponsorship Ministry of Agriculture
• Principles
– System based on Marketing
Authorisation Holder declarations
– Confidentiality ensured
– Simple questionnaire
– 100 % answers
– Check quality of data
• Annual report
http://www.anses.fr/Documents/ANMV-Ra-Antibiotiques2010.pdf
Example: French Antimicrobial Sales/Use Monitoring system
• Based on sales declaration by Marketing
Authorisation Holder (MAH)
– For each sale package of each VMP containing
antimicrobial :
• ID number
•Number of sales
•Species repartition estimate
• Data base on Veterinary Medicinal Products
• Data on number of animals in the country
Database Fields
• VMP Name
• MAH name
• Id Sale package
• Sale package description
• Number of sold units
• Active ingredient
• Quantity of active expressed in mass of the active entity of the
molecule.
• Convertion factor IU/g for some Active ingredients
• Pharmaceutical form
• Route of administration
• Target Species
• Posology mg/Kg
• Treatment duration
21
How to interpret results ?
- Antimicrobial sales volumes do not represent precisely their use
Recent antimicrobials are more potent than old ones, and
less active is needed to be administered to treat animals.
-To estimate animal exposure to antimicrobials it is need to take into account other
factors such as the posology (mg/Kg) and the duration of administration. It is also
needed to take into account the change in the total animal population according to
time
Therefore a decrease in sales volume does not mean obligatorily that there
is a decrease in Antimicrobial use
• Crucial to distinguish between:
- Sales volume
- Exposure to antimicrobials
Theoritical example(1)
In this example, the percentage of treated animals
jump from 11% to 20,5 % meaning that globally the
exposure increase from 86.4 %
How do antimicrobial quantities vary?
Time 1 Time 2
Total animal population (animal number) 1000 1000
Population treated (animal number) 110 205
including treated with oxytétracycline (Animal nb) 10 5
treated with fluoroquinolones (Animal nb) 100 200 0
5
10
15
20
25
Time 1 Time 2
Exposure
Theoritical example (2)
Calculation performed according to the following elements:
•Animal weight: 50 Kg
•Posology: Oxytétracycline : 20 mg/Kg during 3 days
•Posology: Fluoroquinolone: 2 mg/Kg for 1 day
•Calculation: Nb animals x 50 Kg x posology x treatment duration
Results:
In this example, the antimicrobial
quantity decrease from 12.5 %
Time 1 Time 2
Oxytétracycline quantity (mg) 30000 15000
Fluoroquinolone quantity (mg) 10000 20000
Total anttimicrobial quantity (mg) 40000 350000
5
10
15
20
25
30
35
40
45
Time 1 Time 2
Antimicrobial quantity (g)
Theoritical example (3)
In this example, an increase in animal exposure of 86.5 %
results in a decrease of antimicrobial quantity of 12.5 %
Need to define an exposure indicator (see later ALEA
(Animal Level of Exposure)). This indicator is directly
correlated to the number of animals treated.
0
5
10
15
20
25
30
35
40
45
Antimicrobial quantity (mg) Exposure
Time 1
Time 2
Results 2010:
Sales
• 1014 tons sold in 2010
• The lowest sales figure during
the survey period
(-23% in comparison to1999)
(-3,6 % in 2010 compared to
2009) 0,00
200,00
400,00
600,00
800,00
1 000,00
1 200,00
1 400,00
1 600,00
19
99
20
00
20
01
20
02
20
03
20
04
20
05
20
06
20
07
20
08
20
09
20
10
Evolution des ventes d'antibiotiques 1999-2010
(Tonnes)
Decrease due mainly to 2 antimicrobial classes:
Tetracyclines (-153T,-24.5%) Sulfonamides (-86T, -33%)
compared to 1999
Evolution of antimicrobial sales between 1999 and 2010
Estimate of antimicrobial
exposure
Change in antimicrobial exposure 1999-2010 (oral + parenteral route)
The animal exposure to antimicrobials:
- has increased between 1999 and
2007 (+21.8%)
- has decreased in 2008 and 2009 (-12.3)%
- was stabilised in 2010
0
0,1
0,2
0,3
0,4
0,5
0,6
0,7
0,8
19
99
20
00
20
01
20
02
20
03
20
04
20
05
20
06
20
07
20
08
20
09
20
10
Evolution de l'exposition aux antibiotiques 1999-2010
(ALEA)
Change in Exposure 1999-2010 (oral + parenteral route)
• Analysis by route of administration and
pharmaceutical form
0
1 000 000
2 000 000
3 000 000
4 000 000
5 000 000
6 000 000
7 000 000
8 000 000
9 000 000
10 000 000
1999 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010
oral
Other oral
forms
oral solutions
oral
powders
Premixes0
0,1
0,2
0,3
0,4
0,5
0,6
0,7
0,8
1 2 3 4 5 6 7 8 9 10 11 12
Injectable oral
Change in Exposure 1999-2010 (oral + parenteral route)
• Analysis by antimicrobial class
0
0,05
0,1
0,15
0,2
0,25
0,3
1999
2000
2001
2002
2003
2004
2005
2006
2007
2008
2009
2010
Antimicrobials most
often used:
•Tetracyclines
•Polymyxins
•Penicillins
•Macrolides
•Aminoglycosides
Change in Exposure 1999-2010 (oral + parenteral route)
• Analysis by animal species
0
0,2
0,4
0,6
0,8
1
1,2
1,4
1,6
Bovine
Porcine
Poultry
Cat dogs
Change in Exposure 1999-2010 (oral + parenteral route)
• Analysis by animal species by route of administration and
antimicrobial classes
• Example: Porcine
Parenteral route Oral route
0%
5%
10%
15%
20%
25%
30%
35%
40%
1999
2000
2001
2002
2003
2004
2005
2006
2007
2008
2009
2010
Pénicillines
Fluoroquinolones
Aminoglycosides
Macrolides
Tétracyclines
Polypeptides
Sulfamides
Céphalosporines 3&4G
Triméthoprime
Lincosamides
Pleuromutilines
Quinolones
Phénicolés
0%
5%
10%
15%
20%
25%
30%
35%
40%
19
99
20
00
20
01
20
02
20
03
20
04
20
05
20
06
20
07
20
08
20
09
20
10
Tétracyclines
Polypeptides
Pleuromutilines
Sulfamides
Triméthoprime
Macrolides
Pénicillines
Aminoglycosides
Quinolones
Lincosamides
-0,00500
-
0,00500
0,01000
0,01500
0,02000
0,02500
REF
AUTRE
GEN
TOTAL
Poultry – oral route – Fluoroquinolones - generics
Field surveys
• Performed by another Anses Laboratory
based in Ploufragan
• Field survey for Poultry, Porcines, Rabbits
Field survey gives complementary and
more precise information
Example: fluoroquinolones, oral route, Poultry
0,00%
20,00%
40,00%
60,00%
80,00%
100,00%
120,00%
2003 2004 2005 2006 2007 2008
Generics
Reference products
National survey
100 % = mean value
1999-2005
Field studies
European example ESVAC: European Surveillance of Veterinary
Antimicrobial Consumption
European project started in 2009 in order to collect
harmonized data on antimicrobial use in animals at
the European level
1st report: Trends in the sales of veterinary antimicrobial agents
in nine European Countries Reporting period: 2005-2009 http://www.ema.europa.eu/docs/en_GB/document_library/Other/2010/04/WC500089584.pdf
2nd Report: Sales of veterinary antimicrobial agents in 19 EU/EEA
countries in 2010 http://www.ema.europa.eu/docs/en_GB/document_library/Report/2012/10/WC500133532.pdf
Conclusion
• Tool enabling to follow trends in use of
antimicrobials
• Is to be analysed in conjunction with fields
surveys
• This tool and the data obtained is a basis to:
- Make a comparison with antimicrobial resistance data
- To analyse the potential impact or risk management
measures
Recent example of Management measures
• Volontary ban of Cephalosporines in Pigs in
France in 2010
39
0%
5%
10%
15%
20%
25%
30%
35%
40%
45%
50%
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99
20
00
20
01
20
02
20
03
20
04
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08
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Exposu
re
12 rue de Prony, 75017 Paris, France - www.oie.int – [email protected]
Organisation mondiale
de la santé animale
World Organisation
for Animal Health
Organización Mundial
de Sanidad Animal
Thank you for your attention