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Danish Research Centre
for Organic Farming
Status Report 2003 and
Application for Continuation in 2004
For research projects financed by grants from The Directorate for Food, Fisheries and Agro Business under the Danish Ministry of Food, Agriculture and Fisheries

1. Research
Research in organic farming 2000-2005 (DARCOF II)
2. Project title and number
Use of antimicrobials and occurrence of resistance in organic cattle herds
3. Head of project
Frank Møller Aarestrup, DVM, Ph.D. Statens Veterinære Serumlaboratorium Bülowsvej 27 1790 København V
4. Participating
Den Kgl. Veterinær- og Landbohøjskole Grønnegaardsvej 2 1870 Frederiksberg C Dansk Jordbrugsforskning Foulum P.O. Box 50 8830 Tjele Stig Milan Thamsborg, DVM, Ph.D. Den Kgl. Veterinær- og Landbohøjskole Dyrlægevej 10 1870 Frederiksberg C Tlf: 35 28 3778 E-mail: smt@kvl.dk Mette Vaarst, DVM, Ph.D. Dansk Jordbrugsforskning Foulum P.O. Box 50 8830 Tjele Tlf: 89 99 19 00 Fax: 89 99 19 19 E-mail: Mette.Vaarst@agrsci.dk Torben W. Bennedsgaard, DVM , Ph.D. Dansk Jordbrugsforskning Foulum P.O. Box 50 8830 Tjele Tlf: 89991541 E-mail: twb@kvl.dk II.5 "Use of antimicrobials and occurrence of resistance in organic cattle herds" 7. Midterm description of the project, its results and progress, and Project summary
Methods to perform a continuous surveillance for antimicrobial resistance at herd level will be
evaluated and used to compare the occurrence of resistance between organic and conventional
dairy herds. In addition the treatment pattern of animals in organic herds will be studied. Based
upon an eventual relation between treatment patterns and antimicrobial resistance on herd level
or in general guidelines for disease treatment will be developed and implemented as herd specific
treatment strategies which meet the demand for animal welfare and minimises the risk for antim-
icrobial resistance.
The project consists of four work packages
WP1 Monitoring of use of medicine
Establishing of a registration and reporting procedure on the use of drugs for individual animals.
Clinical mastitis is described using a protocol which is developed by the research group in an-
other project.
WP2 Occurrence and dynamics of antimicrobial resistance in dairy herds
Antimicrobial resistance of commensal E. coli is accessed in 20 herds by isolates from fecal sam-
ples of randomly selected animals in two groups: calves up to 3 month old and cows. Samples are
taken at the start and at the end of the project. In five herds samples are taken four times the first
year of the study to evaluate the dynamics on herd level and in relation to season.
Data are analysed together with results from ongoing projects from another 20 organic and 20
conventional herds to describe the pattern and dynamics of resistance and develop a scheme for
monitoring of antimicrobial resistance on herd level.
Data on antimicrobial resistance is combined with data on use of antibiotics and descriptions of
general treatment strategies based on qualitative research interviews.
WP3 Characterization of treatments in organic farms
Systematic clinical registrations of udder health of cows with and without veterinary treatment are
implemented on a monthly basis in five herds, to provide data on treatment strategy and outcome
of antibiotic treatments.
Herd managers are interviewed on treatment routines using qualitative research interviews. Data
are analysed using method triangulation based on grounded theory analysis.
Results of these analyses will be combined with analysis of data on somatic cell counts and milk
production.
WP4 Use of herd specific plans for control of antibiotic resistance
Plans for contol of antimicrobial resistance will be formulated in 10 new herds. The plans should
describe:
- risk areas for antimicrobial resistance - disease prevention plans - herd specific treatment strategy. The herds selected should have a very low use of antibiotics and/or a good herd health at the
time of inclusion.
Dansk sammendrag
Mulighederne for at gennemføre en kontinuer overvågning for antibiotikaresistens vil blive eva-
lueret og anvendt til at sammenligne forekomsten af resistens blandt konventionelle og økologi-
ske besætninger. Behandlingsregimerne vil blive registreret og baseret på eventuelle sammenhæn-
ge mellem behandling og forekomst af resistens vil der blive udviklet retningslinier for behand-
II.5 "Use of antimicrobials and occurrence of resistance in organic cattle herds" ling med henblik på at minimere resistensudviklingen.
Projektet består af fire delprojekter
WP1 Monitorering af medicinanvendelsen
Anvendelsen af medicin registreres I udvalgte økologiske og konventionelle besætninger og for-
bruget sammenlignes.
WP2 Forekomst af antibiotikaresistens
Forekomsten af antimikrobiel resistens bestemmes for E. coli fra fæcesprøver i 20 besætninger
med prøveudtagninger i begyndelsen og afslutningen af projektet. I fem besætninger følges fore-
komsten af resistens med prøveudtagninger hvert kvartal I det første projektår. Data analyseres
for eventuelle sammenhænge mellem forekomst af resistens og medicinforbrug.
WP3 Karakterisering af behandlinger I økologiske besætninger
Der foretages systematiske kliniske registreringer af yversundhed blandt behandlede og ikke be-
handlede køer hver måned I 5 besætninger. Besætningsejere interviewes for at finde ud af på
hvilket grundlag der iværksættes behandlinger.
WP4 Anvendelse af besætningsspecifikke planer til kontrol af antibiotikaresistens
Der vil blive udarbejdet planer til reduktion af antibiotikaresistens I 10 besætninger. Dette viol
inkludere:
- risikofaktorer for antibiotikaresistens - planer for forebyggelse af sygdom - besætningsspecifikke Fem af disse besætninger skal have et meget lille forbrug af veterinær medicin ved inklusion i stu-diet og baseret på erfaringer i disse besætninger vil der blive introduceret planer i de øvrige 5 be-sætninger, hvorefter alle besætninger følges i et år Table A.1: Work package list (from application)
timicrobial resistance in dairy herds TWB, KVL Use of herd specific plans for con- SMT, KVL, 277 * Responsible participants are underlined Objectives and expected achievements
To determine potential differences in the occurrence of antimicrobial resistance between To investigate the possibility to perform a continuous monitoring of antimicrobial resis- tance by evaluating the dynamics of antimicrobial resistance. To characterise the treatment pattern of organic herds and based on this, develop guide- lines for disease treatment which fits the goals for the organic herd, meet the de-mand for animal welfare and minimise the risk for antimicrobial resistance. II.5 "Use of antimicrobials and occurrence of resistance in organic cattle herds" Midterm results and progress
C.1 Description (summary) of main results and conclusions
WP1 Monitoring of use of medicine
A continuous monitoring of medicine usage has been carried out in the first five herds in the pro-
ject. The data shows a considerably variation in the amount and types of antibiotics used in the
herds (table 1). Based on the initial discussion with the farmers and veterinarians on herd visits
the differences seem to relate more to preferences of the veterinarian than to herd specific fac-
tors. These findings are used for the herd plans in wp4.
WP2 Occurrence and dynamics of antimicrobial resistance in dairy herds
Analysis of data on antimicrobial resistance of commensal E. coli shows that the prevalence of
antimicrobial resistance is related to age in the 60 herds examined. Table 1 shows the results of
the initial analysis for calves up to 23 weeks old. The prevalence of antimicrobial resistance was
found to be very low (<5%) among cows in both organic and conventional herds. The sampling
scheme was changed in the first 5 herds based on these findings to sample the same calves at 3
months intervals. The analysis of these samples confirmed the finding that the prevalence of an-
timicrobial resistance decreases with age. Highest level of resistance is found 1 week after birth.
However, the trend of decreasing resistance is broken at the age of 3-4 month. These findings
might be related to treatments for diarrhoea and pneumonia respectively. The results were sub-
mitted for publication in March 2003.The relation between treatment of individual animals and
occurrence of resistance have been analyzed, but no relation has been found in the dataset so far.
No systematic change in resistance related to season was found.
Table 1. Predicted proportion of isolates resistant to streptomycin, sulphamethoxazole, ampicil-
lin, tetracycline, trimetoprim, chloramphenicol and nalidixic acid for calves 9, 60 and 180 days old
and to streptomycin, sulphamethoxazole, ampicillin and tetracycline for cows. Predictions for
calves based on model of 949 Danish isolates of E. coli from 58 herds. Details are published in
Bennedsgaard (2003).
Age of animal
Calves 9 days
Calves 60 days old
conversion 0.27 0.20 0.12 0.12 0.07 0.02 0.00 Calves 180 days old
II.5 "Use of antimicrobials and occurrence of resistance in organic cattle herds" before conversion Converting herds two years conversion 0.02 0.02 0.00 0.01 0.00 0.01 0.00 *STR=streptomycin, SMX=sulphamethoxazole, TET=tetracycline,
AMP=ampicillin, TMP=trimetoprim, CHL= chloramphenicol, NAL=nalidixic acid.
Based on the results it can not be recommended to use E. coli as indicator for antibiotic resis-
tance of adult cattle in diary herds, sampling of calves can be used if the number of animals sam-
pled are relatively large and correction or age are made. However, further investigation into the
reason for herd differences are needed.
WP3 Characterization of treatments in organic farms
The initial interviews were carried out in November-December 2001 based on key figures from
herd data and a step-wise identification of treatment criteria on four different levels (symptom
level, cow level, and the levels of the herd situation and perception of alternatives, respectively,
identified through previous study; Vaarst et al. 2002).
Based on this, expectations and wishes connected to a more explicit future treatment pattern
were discussed with the farmer and in most herds the veterinarian on herd visits in February 2002
in five herds.
An initial model for description of success of treatment and graphical presentations of data on
udder health and use of veterinary medicine has been developed. These tools are being used and
evaluated in the discussion of future treatment strategies in the selected herds, and have been
used for introduction of the project in the next group of herds.
The average number of days of treatment with antibiotics in case of mastitis decreased in most
herds after conversion to organic production in June 1999 (table 2).
Table 2. Mean number of days pr mastitis treatment, five herds.
Data from 1998 to 2002.
Table 3. Use of antibiotics for mastitis treatment in five herds in 2001. Percent of treatments with different groups of antibiotics Antibiotics Mean and streptomycin Broad-spectrum penicillins2 II.5 "Use of antimicrobials and occurrence of resistance in organic cattle herds" 2 Ampicillin, amoxicillin, cloxacillin
A description of the choice of antibiotics and duration of antibiotic treatments has been submit-
ted for publication in March 2003 based on data from this study and a parallel study (Benneds-
gaard,2003). The study concluded that the average length of treatment decreased after conversion
in herds that had access to follow up treatments by the farmer before conversion and that organic
herds differed in the choice of products for intramammary products. In the organic herds prod-
ucts with the shortest withdrawal time of milk was more commonly used.
WP4 Use of herd specific plans for control of antibiotic resistance
Only minor changes in the use of antibiotics were seen in the five herds involved in WP3 in the
first year of the study. One of the obstacles to reducing the use of antibiotics seemed to be the
lack of experience with handling of infection without antibiotics among both farmers and veteri-
narians.
Based on this experience the selection of herds for WP4 has been changed. Five herds that have
used none or only very small amounts of antibiotics were selected in June 2003 together with five
herds with good health status and interest in reducing the use of antibiotics.
These ten herds was visited and interviewed in September 2003. The herds’ treatment and pre-
vention strategies was assessed with the dialog-tool developed in WP3 and by data analysis.
Together with Økologiens Hus focus-group interviews were carried out in October 2003. These
interviews resulted in a number of specific suggestions for improvement in the individual herds.
These are to be carried out and monitored within the next 8-9 months.
C.2 Fulfilment of deliverables and milestones
WP1 Monitoring of use of medicine
Deliverables
Data on disease, use of medicine and clinical cases of Milestones
M3 Establishment of a system for registration of use of drugs and disease in herds M4 Introduction of registration of clinical mastitis
WP2 Occurrence and dynamics of antimicrobial
resistance in dairy herds
Deliverables
3. Determination of the difference in the occurrence of an- timicrobial resistance in conventional and organic dairy herds. (Pu) 6. Description of the dynamics of antimicrobial resistance over time. (Pu) (one publicatioin with D3) II.5 "Use of antimicrobials and occurrence of resistance in organic cattle herds" 8. Description of changes in disease incidence and antim- icrobial resistance after conversion to organic farming. (Pu)
Milestones
M1 Determination of the difference in the occurrence of antimicrobial resistance in conventional and new and old organic dairy herds. M10 Description of the dynamics of antimicrobial resis- tance over time M12 Collection of fecal samples M14 Evaluation of changes in antimicrobial resistance from conversion until 3½ years after conversion to organic
farming.
WP 3, Characterization of treatments in organic
Deliverables
1 Description of the combination of qualitative studies of treatment choices and quantitative data (pu.) 9 Recommendations for treatment strategies in organic Milestones
M1: Selection of herds and implementation of clinical ex- aminations M7: Qualitative analysis on herd level of treatment pat- terns carried out M9: Analysis of data from 5 herds (in depth studies) and 40-45 herds (overall level; standardised health and pro-duction recordings) M15: Recommendations (Danish Report)
WP 4, Use of herd specific plans for control of anti-
biotic resistance
Deliverables
9 Recommendations for treatment strategies in organic dairy herds (Danish Report) 10. Description of the effect of change in treatment strategies on the occurrence of anti-microbial resis- Changed to: Description of differences in use of antimicrobials and occurrence of antimicrobial resis-tance. Milestones
M2 Selection of herds and determination of initial occur- rence of anti-microbial resistance M6 Preparation of herd specific plans M8 Midway evaluation and correction of plans M11 Final evaluation of plans and status of occurrence of April 2003 II.5 "Use of antimicrobials and occurrence of resistance in organic cattle herds" M15 Recommendations (Danish report) including results from WP3 M17 Analysis of change in antibiotic resistance and Description of deviations and subsequent adjustments of plans
There has been some delay in the plan, due to the fact that all contact to herds has been impossi-ble during the last part of the housing period 2001 (early March-June) because of restrictions in connection with the outbreak of foot & mouth disease. The selection of herds and introduction of registrations has there fore been postponed to the late autumn 2001. Data on medicine use and resistance in conventional and old organic herds has been delayed be-cause of extensive work on validation of data from the central databases. The initial sampling of fecal samples showed a very low prevalence of resistance in samples from cows, where as calves samples showed a high level of antimicrobial resistance in very young calves (1-3 month) and less in older calves. Based on these findings the sample plan for fecal samples has been changed to sampling of only 20 calves from 0-6 month of age including calves sampled at the previous visit. One of the five herds in wp2+3 has dropped out of the study because of return to conventional production. The herd will not be substituted by another herd. Only minor changes in the use of antibiotics were seen in the five herds involved in WP3 in the first year of the study. On of the obstacles to reducing the use of antibiotics seemed to be the lack of experience with handling of infection without antibiotics among both farmers and veteri-narians. Based on this it is unlikely that any major changes will take place with regards to antibi-otic resistance. Based on this experience the selection of herds for WP4 has been changed. Five herds that have used none or only very small amounts of antibiotics was selected in June 2003 together with five herds with good health status and interest in reducing the use of antibiotics. The aim of inclusion of these herds is to describe the challenges in adopting the experiences from herds with very low or no use of antibiotics in motivated herds with a good herd health. This is planned to take place from late 2003 until end of May 2004. The change in the selection of the herds has resulted in a delay of the project. The final analysis of data will be carried out in the June 2004 with the final report being finished in August 2004 Thorkild Nissen from Økologiens Hus has been involved in the work in WP4 financed by Øko-logisk Hus. Because of the lack of differences in antibiotic resistance of E. coli between the herd groups and the strong relation between age of the animal and prevalence of resistant E. coli it was decided to access the level of antibiotic resistance in the 10 new herds by isolation of S. aureus milk samples. II.5 "Use of antimicrobials and occurrence of resistance in organic cattle herds" Project publications and other products
1. Articles in international, scientific journals with review procedures Vaarst, M., Thamsborg, S. M., Bennedsgaard T. W., Houe, H., Enevoldsen, C., Aarestrup, F. M. & Snoo, A. de. 2003. Organic dairy farmers decision making in the first 2 years after conversion in relation to mastitis treatment. Livestock Production Science. 80, 1-2, 109-120. * Bennedsgaard T. W., Thamsborg S. M., Vaarst M., Enevoldsen C. 2003. Eleven years with or-ganic dairy production in Denmark – herd health and production related to time of conversion and compared to conventional production. Livestock Production Science. 80, 1-2, 121-131.** Bennedsgaard, T. W., Thamsborg, S. M., Aarestrup, F. M., Enevoldsen, C., Vaarst, M., Larsen, P. B. Use of veterinary drugs in organic and conventional dairy herds in Denmark with emphasis on mastitis treatment. (Submitted)* Bennedsgaard, T. W., Thamsborg, S. M., Aarestrup, F. M., Enevoldsen, C., Vaarst, M. Antibi-otic resistance of Escherichia coli in conventional and organic dairy herds in Denmark. (Sub-mitted)* PAPER V Bennedsgaard, T. W., Thamsborg, S. M., Aarestrup, F. M., Enevoldsen, C., Vaarst, M., Christof-fersen, A. B. Resistance of Staphylococcus aureus isolates from cows with high somatic cell counts in organic and conventional dairy herds in Denmark. (Submitted) 2. Papers presented at congresses, symposiums, etc. 3. Reports, articles in agricultural journals, etc. 4. Oral presentations, public meetings, field days, etc. “Reduced use of veterinary drugs in organic dairy herds – potentials and consequences”, Midterm seminar for ph.d. student Torben Werner Bennedsgaard, October 1, 2001, KVL * Vaarst, M. 2002. Strategi i stedet for antibiotika [Strategy instead of antibiotics. In Da-nish]. Økologisk Jordbrug, 14. Juni 2002, s. 11. Nielsen, K.M. Mange yverbetændelser er forudsigelige. [Many mastitis cases are predic-table. In Danish]. Økologisk Jordbrug, 14. Juni 2002, s. 11. Bennedsgaard, T. W. “Mastitis treatment, success or failure” Presentation at meeting for farmers and veterinarians, The Danish Dairy Board, Rødding, 30. January 2002. Bennedsgaard, T. W. 2003. “Reduced use of veterinary drugs in organic dairy herds – potentials and consequences”. Ph.D. dissertation, The Royal Veterinary and Agricultural University, Frederiksberg, Denmark. * II.5 "Use of antimicrobials and occurrence of resistance in organic cattle herds" Scientific education
Elements of the project is part of Torben Werner Bennedsgaards ph. d. study. Arno de Snoo, Scottish Agricultural College, completed a Master thesis within the project with Mette Vaarst as supervisor during two stays (4½ months in total) in 2002 at Danish Institute of Agricultural Sciences, Department of Animal Health and Welfare. Master the-sis: Farming styles in Danish organic dairy farming and the relations to health strategies with an emphasis on mastitis treatments. DIAS, pp. 89. National and international cooperation
Research stay at Professor Paul Bartlett, Michigan State University by Torben Werner Ben-nedsgaard March-April 2001. Thorkild Nissen, Økologiens Hus (WP4) Critical reflection on the project
The monitoring of antimicrobial resistance has been successful giving new information on the dynamics of resistance of commensal E. coli on herd level and in relation to age of dairy calves. The ability to change in sampling scheme has given a data set which is better suited for describing the marked variation in prevalence of resistance with age. However, to describe the level of resis-tance in a given herd a sampling scheme in which a few calves at a given age (2-3 weeks old would be optimal) was sampled would give a more comparable picture. Such a sampling scheme is not easy to implement in the actual research project since it would required a largely increased number of herd visits which should be planed after the birth of calves in the single herd. The budget of the project does not allow such a change. The rapid decrease in prevalence of antimicrobial resistance means that only a limited number of animals can be used in the analysis of relations between antibiotic treatment and antimicrobial resistance. Based on interviews with farmers and results from another project isolation of S. aureus from milk samples will be used in the last part of the project. Penicillin resistance of S. aureus may have im-pact of the choice of antibiotics for mastitis treatment, the disease that accounts for the largest part of the use of antibiotics in dairy herds. The initial meetings with farmers and veterinarians have given important knowledge in the differ-ent roles in the decision process before eventual antibiotic treatment. The risk of development of antimicrobial resistance is normally not a subject in this decision process, and the research group places an important role in the introduction of this new problem to the process. The role of the research group in the process in the single herd will have to be evaluated together with the con-tributions from the farmer and the veterinarian in the evaluation of the project. The combination of research methodology (quantitative and qualitative) and the use of participa-tory methods are very depending on the collaboration between researches, an well-described dis-tribution of tasks and responsibilities, and a group of farmers and veterinarians, who contribute to the project in the way which is beneficial for the project. II.5 "Use of antimicrobials and occurrence of resistance in organic cattle herds" II.5 "Use of antimicrobials and occurrence of resistance in organic cattle herds"
8. Budget
Account for any change in budgets
Budget for the whole project (1.000 DKK)
Total consumption of funds from DARCOF and expected consumption this year and coming years
Comments:

II.5 "Use of antimicrobials and occurrence of resistance in organic cattle herds"
9. Signatures and stamps
II.5 "Use of antimicrobials and occurrence of resistance in organic cattle herds"
Appendix I.
A. Budget for each participating institute (1.000 DKr)
Name of Institute: Den Kgl. Veterinær og Landbohøjskole Year: Consump-
Comments:
Due to the delays in the consumption in 2001 and 2002 have been reduced and the
budget for 2003 increased.
Changes in budget in parenthesis (Revised overall budget as approved by DFFE,
August 2003 (J. nr. 3501-62-03-80))
Consumption in 2003 results in over-expenditure on technical personnel of ca. 8%
II.5 "Use of antimicrobials and occurrence of resistance in organic cattle herds" Budget for each participating department (1.000 DKK)
Name of Institute: Danmarks Jordbrugsforskning, Year: Con- 37,3 13,4
223,8 80,4
II.5 "Use of antimicrobials and occurrence of resistance in organic cattle herds"
Name of Institute: Danish Veterinary Institute

Year: Consump-
Other operational costs 50.000 40.000 10.000
Comments:


II.5 "Use of antimicrobials and occurrence of resistance in organic cattle herds"

Source: http://www.okoforsk.dk/projekt/foejoII/ii05/stat03_febr04.pdf