DANMAP Danish Integrated Antimicrobial Resistance Monitoring and Research Programme Hanne-Dorthe Emborg Department of Microbiology and Risk Assessment National Food Institute, DTU
Introduction The DANMAP programme was initiated in 1995 Objectives are: Monitor consumption of antimicrobials for food animals and humans Monitor the occurrence of antimicrobial resistance among bacteria from food animals, food of animal origin and humans Study associations between antimicrobial consumption and antimicrobial resistance To identify routes of transmission and areas for further research
The DANMAP participants Statens Serum Institute The Danish Veterinary and Food Administration The Danish Medicines Agency National Food Institute and National Veterinary Institute, DTU The results are published yearly
Considerations (1) Purpose of the surveillance programme Trend Early warning Estimate associations between consumption and resistance Effect of interventions Guide to antimicrobial use policies Methods identical methods MIC-values Active / passive surveillance
Considerations (2) Sampling scheme The sampling frame should cover all epidemiological unit of the national production A representative sample collected randomly The epidemiological unit for broilers and turkeys is the flock For pigs and cattle the epidemiological unit is the holding Sampling procedure remains constant Comparable samples between populations
Herds 2002-2006
DANMAP Herds 2002-2006
Passive surveillance Passive: Diagnostic submissions from veterinarians and human doctors Isolates from the existing Salmonella surveillance programmes Advantage and disadvantage: Low cost, large number of isolates Representing worst cases, often not a representative sample
Active surveillance Active: Extra samples that are collected on our request, we design the sampling strategy The samples are from healthy animals, humans and from foods (slaughterhouses, retail outlet e.g. supermarkets) Advantage and disadvantage: Knowledge about the level of resistance in the normal population and in food, we have influence on the sampling scheme Each sample has a price, often not a large number of isolates
Bacteria included in the programme Genus Indicator Pathogens Zoonotic E. coli + + Enterococci + Staphylococci + Streptococci + Salmonella + Campylobacter +
Isolates from food animals Random sampling of herds at slaughter Broilers - 95% of population Pigs - 95% of population Cattle - 90% of population Diseased population Almost 100% national coverage of poultry, pigs and cattle
Isolates from food Nationwide collection of samples at wholesale and retail outlets Samples are collected from pre-determined categories Imported foods are sampled for Salmonella at point of entry
Isolates from humans Results of routine testing of various pathogens in fourteen major hospitals Data from testing of Campylobacter and Salmonella submitted to the central public health laboratory Enterococci and E. coli isolated from stools from approx. 200 healthy humans (random sample)
No. of isolates per year Animals Food Humans E. coli (pathogens) <50 - >10,000 Salmonella 600 90 700 Campylobacter 200 250 130 E. coli (indicator) 350 (700) (50) Enterococci 420 (1,100) (60) Streptococci >1,000 Staphylococci <50 2,000
Information available for each isolate Isolates of animal origin Farm of origin (Central Husbandry Register number), animal species, bacterial species, sampling date, results of the susceptibility testing Isolates from food Food product, country of origin of food product, bacterial species, sampling date, results of the susceptibility testing Isolates from humans Hospital or county of origin, bacterial species and results of the susceptibility testing
Susceptibility testing Bacteria from animals and humans: MIC-determination using Sensititre or agar dilution MIC Some bacteria from humans tested in hospitals: disk diffusion In DANMAP 2007, cut-off values were used to report the results off the susceptibility testing for all zoonotic and indicator bacteria from animals, food and humans
Food animals Veterinary practice Private Laboratories Slaughter plants Samples Isolates Samples Diagnostic submission National Food Institute and National Veterinary Institute VetStat Data Humans Foods Regional Food Control laboratories Regional hospital laboratories Samples General practice Samples Isolates Isolates / data Data Data Statens Serum Institut DANMAP Data Danish Medicine Agency
100 DANMAP 2007 80 60 40 20 % resistant isolates 0 1994 1995 1996 1997 1998 1999 2000 2001 2002 2003 2004 2005 2006 2007 30.000 Kg active compound Avoparcin consumption and resistance to avoparcin among E. faecium Avoparcin Broilers Broiler meat Humans 25.000 20.000 15.000 10.000 5.000 0
Trends in erytromycin resistance among E. faecium 80.000 DANMAP 2007 100 Kg active compound 70.000 60.000 50.000 40.000 30.000 20.000 10.000 80 60 40 20 % resistant isolates 0 1994 1995 1996 1997 1998 1999 2000 2001 2002 2003 2004 2005 2006 2007 Period Macrolides_vet Macrolides_hum Pigs Pork Humans 0
Consumption of antimicrobials commonly used to treat infections caused by Gram negative bacteria in animals 45000 40000 Kg active compound 35000 30000 25000 20000 15000 10000 5000 0 1996 1997 1998 1999 2000 2001 2002 2003 2004 2005 2006 2007 Tetracycline Extended spectrum penicillins Aminoglycosides Sulfonamides/TMP
Trends in resistance among S. Typhimurium from pigs 60 DANMAP 2007 50 % resistant isolates 40 30 20 10 0 1997 1998 1999 2000 2001 2002 2003 2004 2005 2006 2007 Tetracycline Chloramphenicol Ampicillin Nalidixic acid Sulfonamide Ciprofloxacin
Trends in resistance among indicator E. coli from pigs 70 60 DANMAP 2007 % resistant isolates 50 40 30 20 10 0 96 97 98 99 00 01 02 03 04 05 06 07 Ampicillin Nalidixic acid Streptomycin Sulfonamide Tetracycline
Comparison of resistance in Campylobacter jejuni DANMAP 2004 Compound Cattle Broilers Broiler meat Humans Danish Danish Danish Imported Domestically Travel abroad acquired a) % % % % % % Tetracycline 0 5 1 49 24 42 Erythromycin 0 1 0 3 5 8 Ciprof loxacin 2 5 3 48 29 58 Nalidixic acid 2 5 3 48 31 50 Number of isolates 42 77 103 101 107 12
Trends in C. jejuni resistance DANMAP 2007 80 70 Danish broilers Danish broiler meat Imported broiler meat Domestically acquired a) Travel abroad % resistant isolates 60 50 40 30 20 10 0 97 98 99 0001 02 03 0405 06 07 01 02 0304 05 06 07 01 02 0304 05 06 07 97 98 9900 01 02 03 04 05 0607 06 07 Erythromycin Nalidixic acid Tetracycline
VetStat Surveillance of the consumption of antimicrobials in animals
VetStat (1) Monitors the use of all prescription medicines in animals in Denmark In production animals: the therapeutic use of medicine, sera and vaccines and coccidiostats are registered at farm level The prescription includes information about: farm identity, animal species, age group, diagnosis, name and quantity of the drug and the identity of the veterinarian Medicines used and sold by veterinarians themselves is reported at a similar level of detail Medicines used for companion animals are monitored but at a less detailed level Feed mills report all sales of medicated animal feed and feed containing coccidiostats
VetStat (2) Objectives Provide a basis for research on the association between the use of antimicrobial agents and resistance Provide a basis for the elimination of unnecessary and improper use of antimicrobials Analysis of prescription habits Tools for the veterinarians
2007 Consumption of antimicrobials 1990-2007 DANMAP 2007 200 160 120 80 Antimicrobial (tonnes) 40 0 1990 1991 1992 1993 1994 1995 1996 1997 1998 1999 2000 2001 2002 2003 2004 2005 2006 Prescribed human antibacterials Prescribed veterinary antimicrobials Antimicrobial growth promoters
Antimicrobial consumption by county 2002-2004 8] ]8;9] ]9;10] ]10;11] ]11;12] ]12;13] ]13 ADDkg / kg live pig / county
Consumption of cephalosporins in animals 140 In cattle: 41 kg i 2001 and 92 kg i 2007 In pigs: 24 kg i 2001 and 129 kg i 2007 In pigs, 83 % is used for sows and piglets Kg active compound 120 100 80 60 40 20 0 2001 2002 2003 2004 2005 2006 2007 Systemic treatment of pigs Systemic treatment of cattle Intramammary treatment of cattle
ESBL producing bacteria from animals Until August 2003 ESBL producing E. coli and Salmonella from animals and food was not detected in Denmark The first cases of ESBL producing bacteria was found in imported food and animals In 2005, the first ESBL producing E. coli was detected in Danish animals In 2006, ESBL producing E. coli was detected in 7 cases and in 2007 it was 23 cases 3.5 3.0 2.5 incidence (percent) 2.0 1.5 1.0 0.5 0.0 2004 2005 2006 2007 ESBL producing E.coli from diseased pigs ESBL producing E.coli from diseased cattle
Conclusions DANMAP provide a resistance baseline DANMAP records trends in antimicrobial resistance Overall, levels of resistance reflect consumption of antimicrobials With VetStat the possibility to demonstrate association between the use of antimicrobial agents and resistance is improved A tool to follow national interventions