ANTIMICROBIAL USE ON DAIRY FARMS IN ALBERTA, CANADA Student: Sjoerd Bruil Veterinary student, Faculty of Veterinary Medicine, Utrecht University, The Netherlands. S.H.Bruil@students.uu.nl Supervisors: H.W. Barkema Faculty of Veterinary Medicine, University of Calgary, Canada R. Jorritsma Faculty of Veterinary Medicine, Utrecht University, The Netherlands. 4 October 2008 – 20 January 2009 Antimicrobial use on dairy farms in Alberta S.H. Bruil TABLE OF CONTENTS TABLE OF CONTENTS ........................................................................................................... 2 ABSTRACT ............................................................................................................................... 3 INTRODUCTION ...................................................................................................................... 3 Regulations ............................................................................................................................. 3 Economic considerations........................................................................................................ 4 Use of antimicrobials in dairy farming .................................................................................. 5 The veterinarian ...................................................................................................................... 5 Transmission of AMR from animals to humans .................................................................... 5 MATERIALS AND METHODS ............................................................................................... 6 Herd selection ......................................................................................................................... 6 Questionnaires ........................................................................................................................ 7 Collection of the data ............................................................................................................. 7 Data/statistical analysis .......................................................................................................... 7 RESULTS................................................................................................................................... 8 Descriptive results .................................................................................................................. 8 Products used.......................................................................................................................... 8 DISCUSSION .......................................................................................................................... 11 Data ...................................................................................................................................... 11 ACKNOWLEDGEMENTS ..................................................................................................... 12 REFERENCES ......................................................................................................................... 13 2 Antimicrobial use on dairy farms in Alberta S.H. Bruil ABSTRACT Antimicrobial use was measured for 17 months on dairy farms that participated in the Canadian Bovine Mastitis Research Network in Alberta. In total, 1490 cows were present on 13 farms. Forty different products were found that contained 19 different ingredients. In total, 14.5 grams of active ingredient was used per cow per year and 65.1% was administered by injection and 25.1% was used for intra uterine infusion. The remaining part was infused intramammarily, used as medicated feed, or applied orally. The most frequently used active ingredient were Trimetroprim Sulfonamid (30%), tetracyclines and oxytetracyclines (38%). Penicillins contributed 11% to the total amount. Herd size was negatively correlated with antimicrobial use. INTRODUCTION Since the introduction of antibiotics with penicillin in 1928 and the use of it as a drug 10 years later, the world has to cope with antimicrobial resistance. This is a problem that we experience throughout the whole world in the human and veterinary medicine. Antibiotics are the most commonly used drugs in veterinary practice. Globally, an estimated 50% of all antimicrobials produced are used for veterinary purposes (Teuber 2001). Antimicrobial drugs can be used for several purposes (therapeutic, prophylactic and metaphylactic purposes, and growth promotion) by different routes of administration (Schwarz et al., 2001). Antimicrobials for prophylactic purposes and growth promotion are not granted in every country through the world, but they are allowed by the federal government of Canada and not all antimicrobials have to be prescribed by a veterinarian, but they can also be bought by Over The Counter (OTC) sale and administered to food producing animals without the interference of a veterinarian (Health Canada, 2002). This does of course not contribute to prudent use of antimicrobials. Unfortunately, antimicrobial resistance (AMR) emerges potentially from the use of antimicrobials, and the subsequent transfer of resistance genes and bacteria among animals and animal products and the environment (Schwarz and Chaslus-Dancla, 2001). Therefore, it can become harder to cure infectious diseases in dairy cows and that makes it so important to know how much antibiotics are used for food animals to map these AMR problems. Some inventory studies have been performed to determine the use of antimicrobials on dairy farms and there are organisations (under federal supervision) throughout the world that monitor the use of antimicrobials and AMR (e.g., CIPARS in Canada and MARAN in The Netherlands). Not every country has such a surveillance system and the biggest part of the reports are about the AMR that occur in the country where the reports are published instead of the total use of antimicrobials. Furthermore, several federal governments have established restrictions on the use of antimicrobials to prevent the spreading of AMR. This report contains results that are obtained from the Canadian Bovine Mastitis Research Network (CBMRN) and is specific on the use of antimicrobial on dairy farms in Alberta, Canada. The results can be used to determine if there are any relations between antimicrobial use and herd health and AMR on dairy farms in Alberta, Canada. Regulations The Canadian Federal government has a regulatory role with relation to antimicrobial drugs. Health Canada regulates the sale of drugs in Canada through the Food and Drugs Act and Regulations, and the Controlled Drug and Substance Act. For veterinary drugs, including antimicrobials for food animals, these legislations are administered primarily through the 3 Antimicrobial use on dairy farms in Alberta S.H. Bruil Veterinary Drugs Directorate (VDD). The VDD is responsible for human food safety issues pertaining to veterinary drugs (Health Canada, 2002). The VDD administers the pre-market evaluation of drugs, restricts drug availability, determines drug quality standards, establishes control regulations, evaluates new drugs for use in animals and may allow manufacturers to investigate for new drugs by clinical evaluations and experimental studies. Manufacturers have to submit information and data about the following properties of the drug before the drug can be marketed in Canada: Product quality, including manufacturing process, chemistry, purity, stability, and other similar information, Animal safety, toxicology and efficacy in each intended species, including food and companion animals, and Human safety, toxicology, residues and any other residual outcomes, such as antimicrobial resistance, via the treated animals. There are no specific methods or criteria available to determine human safety or animal safety. The federal regulations divide veterinary antimicrobials into those that can be sold without prescription (OTC) and those that can be sold with prescription. Pharmacists, veterinarians and approved layperson outlets are allowed to sell antimicrobials. Antimicrobials used in medicated feed that are approved by Health Canada are listed in the Canadian Compendium of Medicated Ingredients Brochure (CMIB). These antimicrobials can be used for medicated feed without a veterinary prescription and consequently sold OTC. A drug that has only a therapeutic approval cannot be used as a growth promoter, even not under a veterinary prescription. Each province in Canada has its own regulatory body with the right to regulate more stringently, but not more leniently, the sale of drugs once they are approved at the federal level. In Alberta, all antimicrobials are regulated by the Alberta Livestock Disease Act, implemented by the Alberta Department of Agriculture. Permits for selling of OTC antimicrobials are not only a privilege to veterinarians, but also to licensees under the Veterinary Profession Act to sell these antimicrobials and restricted to veterinarians, permit holders operating at OTC retail outlets, and through medicated feeds prepared according to the Feeds Act (Health Canada, 2002). The availability of OTC antimicrobials may contribute to antimicrobial resistance because there is no direct professional supervision on the use of these products. OTC use does not match with the principles of prudent use of antimicrobial drugs; treatments can be administered inappropriately, for incorrect periods of time, for the wrong illness, by the wrong route or in insufficient doses. Producers rarely ask for the advice of a veterinarian for the use of OTC antimicrobials. Economic considerations By common understanding, modern animal agriculture, including dairy farming, is practised with the intention of returning a profit to the producer. Because of this, two economic considerations strongly influence the choice of acting for the livestock producer. The first is that many diseases can affect more than one individual so that whole groups can be affected. It can, therefore, be more beneficial to prevent a disease than just curing diseased animals. This policy can prevent losses by death and lower performance that often go together. These preventive measures can be done in several ways: adequate nutrition, appropriate husbandry, immunization, and proper sanitation and isolation. For a lot of infectious diseases, it can also be useful to use prophylactic antibiotics, especially during periods of low immune levels in individuals. 4 Antimicrobial use on dairy farms in Alberta S.H. Bruil The second economic consideration is the use of antimicrobials as an enhancement of certain production parameters (e.g. growth promotion). This use is driven by a positive effect instead of prevention of an infectious disease that can cause many losses. The farmer has the option to choose for antimicrobials in different levels and several products. This makes it easy for him/her to choose the option of using antimicrobials as a prophylaxis or for growth promotion (Gustafson and Bowen, 1997). Use of antimicrobials in dairy farming The dairy producer is focused on milk production instead of meat production. Milk production is lower when diseases occur and this could be limited by antimicrobial treatment because the milk obtained from a treated cow cannot be used for human consumption. It is, however, in most cases economically beneficial to treat lactating cows when they suffer from a disease (Sischo, 2006). Additionally, antimicrobials are often routinely administered at dry off to dairy cows to prevent mastitis during the nonlactating period (McEwen and FedorkaCray). Calves and non-lactating cows can receive antimicrobials because they do not produce any milk yet and there are no direct economical or safety restrictions for these animals. Young calves are fed with milk or milk replacer (which may contain tetracycline) for 6-8 weeks and diarrhoea and pneumonia are important diseases of dairy calves and antimicrobials can be administered to prevent or treat these infectious diseases (Sischo, 2006) The veterinarian In Canada, as in most countries, veterinarians in food-animal practice obtain a portion of their income from the sale of antimicrobial drugs, and the veterinarian is therefore in a position with different interests; the veterinarian is the diagnostician, the prescriber of antimicrobials, and the owner of a drug inventory. If OTC antimicrobials become limited by prescription only sale, veterinarians will be placed even further in a position of conflict of interest (Health Canada, 2002). Transmission of AMR from animals to humans The administration of antimicrobial agents in animals raises a potential risk for the selection of bacteria for resistance to antimicrobial agents. The AMR depends on the antimicrobials that are administered, but it is also influenced by a number of other factors such as: The availability of pre-existing resistance genes, The exchangeability of the resistance genes and their functional activity in different bacterial hosts, and The selection pressure (Schwarz et al, 2001). It is believed that antibiotic resistance in animals contributes to resistance in human infections. But there is disagreement in the literature, e.g. Bywater (2000) writes: “the part of antibiotic resistant infections in humans that have their origin from animals is very minor with the exceptions of some resistant zoonotic pathogens.” In contrast, Bogaard (2000) states that the problems with AMR should not be underestimated, and that there are very high risks for resistant bacteria causing infections in humans due to the use of antimicrobials in food animals. This author also mentions that further research is essential to quantify the risks that are accompanied by the possible exchange of AMR pathogens (Bogaard, 2000). Another manuscript states that bacteria inevitably develop AMR in animals, including opportunistic pathogens, commensal bacteria and food-borne pathogens (Teuber, 2001). The same AMR genes and gene transfer mechanisms can be found in the commensal microflora of humans and animals. Environments of animals and human get in contact with each other by food, water or direct contact, providing the exchange of possible AMR pathogens (Teuber, 2001). 5 Antimicrobial use on dairy farms in Alberta S.H. Bruil Literature did not succeed yet to completely quantify the association between AMR in humans and animals with antimicrobial usage in food animals. Still, the WHO is concerned about the growing prevalence of AMR and has developed a framework of recommendations to reduce the overuse and misuse of antimicrobials in food animals for the protection of human health. Their main priorities are: Require obligatory prescriptions for all antimicrobials used for disease control in food animals, In the absence of a public health safety evaluation, terminate or rapidly phase out the use of antimicrobials for growth promotion if they are also used for treatment of humans, Create national systems to monitor antimicrobial usage in food animals, Introduce pre-licensing safety evaluation of antimicrobials with consideration of potential resistance to human drugs, Monitor resistance to identify emerging health problems and take timely corrective actions to protect human health, and Develop guidelines for veterinarians to reduce overuse and misuse of antimicrobials in food animals (WHO, 2001). Unfortunately, the federal government of Canada has no proper surveillance program for the monitoring of antimicrobial usage and AMR in food producing animals. The focus of the program is more aiming for the antimicrobial use and AMR in pigs and poultry. There are particularly good records kept on Salmonella spp. and Escherichia coli, but data about dairy farms are not available (Government of Canada, 2007). Antimicrobial resistance is a hot subject and opinions about the subject differ. For this reason, further research is needed to fully understand what is going on, but moreover it will also be possible to adapt policies about antimicrobial usage to create a better system to limit the spreading of AMR. The CBMRN focuses on mastitis on Canadian dairy farms. A part of this research project is also about antimicrobial use and AMR. This report quantifies antimicrobial use on dairy farms in Alberta, Canada. MATERIALS AND METHODS The study was conducted from February 2007 till December 2008. This report is a part of the CBMRN project and only the data obtained until June 2008 are used for this report (17 months of data collection). The following information is mainly provided by the CBMRN. The data used for this report are only collected in the province of Alberta. Herd selection The herds that participated in the project were selected by the following selection criteria, noted that the criteria focused on milk sample collection. The first condition was housing type: a certain portion of herds that participated in the project had to have free-stall housing for their lactating cows. This portion is comparable with the percentage of free-stalls in Alberta. The second condition was bulk tank somatic cell count (BTSCC): BTSCC is obtained directly from candidate farms or their veterinarians, and herds were enrolled in three strata of the most recent 12-month period (uniform across the entire cohort): 1) ≤ 150,000 cells/ml, 2) between 150,000 cells/ml 300,000 cells/ml, or 3) > 300,000 cells/ml. The third 6 Antimicrobial use on dairy farms in Alberta S.H. Bruil condition was breed: herds with fewer than 80% Holstein-Friesian lactating and dry cows at time of enrolment were excluded. Non-Holstein-Friesian cows could be sampled for clinical mastitis, they were not enrolled in the dry cow/fresh cow portion of the study, and were excluded of any intensive sampling. The fourth condition concerned the milking schedule: herds had to follow a 2 times daily milking schedule, and herds that used robotic milking were excluded. All herds participated in data collection through Dairy Herd Improvement (DHI) in their region. The project started with 17 herds in Alberta and 13 herds finished the period of the data collection. The reasons for drop outs were, fire burned down the buildings of one farm, two farm stopped farming activities, and another farmer was asked to withdraw because of insufficient quality of data collection. Farmers/farms’ names were converted into numbers for privacy reasons. Questionnaires Four questionnaires were conducted by the CBMRN technicians on the farms during the collection period. The first two were done in the 11th and 12th month of the collection period and the 3rd and 4th questionnaire were done in the 16th and the 17th month of the data collection. There was also one additional questionnaire per farm conducted by the project technician at the end of the collection period. The goal of the questionnaires was to obtain more (technical) information about the farms, and the questions included a variety of topics, such as milking management, health records, expansion status and hygiene measures. The questionnaires were designed by a PhD student, who is also working half-time for the CBMRN. Each questionnaire took approximately 30 to 60 min to complete and was administered during a farm visit by the project technician. Each farmer completed the four questionnaires (response 100%). Some of the answers obtained from the questionnaires are used in this report. Collection of the data An inventory of all treatments on the dairy farms was performed by providing garbage cans for every farm that participated in the CBMRN project. The farmers were asked to put every treatment packing (empty bottles, tubes, syringes) in the garbage can. The cans were emptied and the drug containers were counted every month by the project technician using a tally worksheet. If there was a treatment in the garbage bag that was not on the tally worksheet, the name, DIN (Drug Identification Number), the manufacturer and the active ingredients of the drug were noted in the extra space on the worksheet. The farmers were asked to keep records of the animals that were treated with antimicrobials in a binder that was provided by the CMBRN. The records were copied for the data collection at every farm visit. The farmer was also questioned about the use of the antibiotics when he/she was around on the farm during a counting (CBMRN, national Cohort reference manual). Data/statistical analysis All data were entered into a spreadsheet program (Microsoft Access; Microsoft Corporation, Redmond, Washington, USA) after the data collection. The data was recorded in total grams of active ingredient used on a farm during the data collection period and adjusted to represent the use for one year instead of 17 months. 7 Antimicrobial use on dairy farms in Alberta S.H. Bruil RESULTS Descriptive results The number of farms that completed the garbage can audit represents approximately 2% of the total number of dairy farms in Alberta (Alberta Milk, Edmonton, Canada). Participating farms were geographically located in the southern half of Alberta, between Edmonton and Calgary. The housing types were: 9 free-stall barns, 2 tie-stall barns and 2 barns with a bedding pack. The herd size per farm changed during the project; because of that reason the average herd size per farm over the period of the data collection is used. Figure 1: number of cows on farm 350 300 number of cows 250 200 150 100 50 0 1 2 3 4 6 7 8 11 12 15 17 18 19 average Farm # Figure 1 shows the number of cows per farm that participated in the project. The figure shows variety among the herds. In total there were on average 1490 cows present during the project. Average number of lactating cows per herd was 95, while there were 19 dry cows present per herd (114 in total). Farm #3 had a herd size of 293 cows (the largest) and farm #8 had a herd size of 60 cows (the smallest). There are no data available of the size of the total herd (calves), but all farms bred their own young stock. Products used Forty different products were used that contained 19 different active ingredients (a group of several active ingredients in one product is counted as one active ingredient) (Table 1). 65.1% was administered by injection, 25.1% was used for intra-uterine infusion, 7.7% is intramammarily administered, 0.1% was used as medicated feed, and 2.0% was orally applied. 8 Antimicrobial use on dairy farms in Alberta S.H. Bruil Table 1: Antimicrobial products that were used on the 17 Alberta dairy farms in Grams of active ingredient. active ingredient Ceftiofur Cephapirin Benzathine Cephapirin Sodium Cloxacillin Benzathine Depocilline enrofloxacin Florfenicol Gentamycin sulfate Monensin Oxytetracycline Oxytetracycline HCl Oxytetracyline Penicillin G Procaine Penicillin G Procaine, Dihydro1) Penicillin G Procaine, Novobiocin pirlimycin HCL procaine penicillin G, benzathine penicillin G Sulphaguanidine Tetracyclin HCl Tetracycline HCl Tilmicosin Tmp/S2) tulathromycin Total 1) 2) Average Use per Total Total in 12 per year cow per (grams) months per farm year 295 208.24 16.02 0.140 90.8 64.09 4.93 0.043 43.6 30.78 2.37 0.021 1491 1052.47 80.96 0.706 1728 1219.76 93.83 0.819 25 17.65 1.36 0.012 705 497.65 38.28 0.334 30 21.18 1.63 0.014 25.45 17.96 1.38 0.012 100 70.59 5.43 0.047 2055 1450.59 111.58 0.974 900 635.29 48.87 0.426 3330 2350.59 180.81 1.578 658.75 465 35.77 0.312 44.88 31.68 2.44 0.021 40.2 28.38 2.18 0.019 63.0 2.9 600 8080 1050 9300 20 30679 44.47 2.05 423.53 5703.53 741.18 6564.71 14.12 21655 3.42 0.16 32.58 438.73 57.01 504.98 1.09 1666 0.030 0.001 0.284 3.828 0.497 4.406 0.009 14.533 Penicillin G Procaine, Dihydrostreptomycin, Novobiocin, Polymyxin B Sulfate Trimetroprim Sulfonamid 9 Antimicrobial use on dairy farms in Alberta S.H. Bruil Figure 2: use of active ingredient per cow per year 5 4.5 4 3.5 Grams 3 2.5 2 1.5 1 0.5 illi ne En ro flo xa ci n Fl or fe ni O co xy l te tra c Su yc lin lp ha e gu an id in e Ti lm ic os Tu in la th ro m yc in Tm p/ S 1) C ep ha pi Pr rin oc C Pe lo xa n G ci llin ,B en z Pe n G Pr G oc en ta pe m n yc G in ,N ov ob io ci n Te tra cy cl in e Pr oc P Pr en oc G Pe Pi n r l im G ,D yc in ih yd ro st re 2) M on en si n C ef D ep oc tio fu r 0 Active ingredient 1) 2) Trimetroprim Sulfonamid Penicillin G Procaine, Dihydrostreptomycin, Novobiocin, Polymyxin B Sulfate In total 14.5 grams of antimicrobials was used per cow per year; 30% of that consisted of trimetroprim sulfonamid (4.4 grams). The amount of tetracyclines used was 28% (4.1 grams) and that of oxytetracyclines was 10% (1.45 grams). Together they represent 38% of the total use. The part of penicillin G was 11% (1.57 grams) and the remaining 21% consisted of the other antimicrobials that were used. Figure 3: antimcrobials used compared with herd size 350 300 250 200 # of cows on farm Grams of antimicrobials used 150 100 50 0 8 18 11 17 15 19 12 4 7 6 1 2 3 Farm # 10 Antimicrobial use on dairy farms in Alberta S.H. Bruil Figure 3 shows the association between herd size and antimicrobial use per cow. The farms on the x-axis are ordered according to herd size (from small to large). Herd size tended to be negatively correlated with use of antimicrobials per cow per year. DISCUSSION The OTC sale of antimicrobials is forbidden in many industrialized countries. Canada is one of the few industrialized countries that (still) allows OTC sale of antimicrobials for food animals. Changing the system to a prescription-only system seems to be an obvious step for ascertaining prudent use of antimicrobials, despite some socio-economic arguments against a prescription-only system; the cost for animal health care in a prescription-only system will probably become higher and producers are worried that there will not be any competition about veterinary drug prices any more in the marketplace. This could, however, be intercepted by price ceilings (Health Canada, 2002). A proper surveillance program for antimicrobial usage in Canada for the whole food animal sector does not (yet) exist. CIPARS (Canadian Integrated Program for Antimicrobial Resistance Surveillance) is focused on the AMR of Salmonella spp. and Escherichia coli. These are foodborne pathogens and therefore more important for CIPARS. Although the WHO recommends to monitor all antimicrobials used in the whole sector and to include more bacteria for AMR (WHO). The utilization of medicated feed for young stock in dairy farming (and other farming) is discussed at the moment. Many countries (e.g. the northern countries in the EU) have banned the use of medicated feed. The VDD in Health Canada is responsible for granting medicated feed in Canada and at the moment they are collecting data about the impacts of the use of medicated feed on humans and animals. The analysis of these data is crucial for the development of new policies about medicated feed (PHAC). Data Alberta is a large province with different environmental circumstances in different places in the province; most farms are therefore located in the southern half of Alberta between Calgary and Edmonton. However, the characteristics of the enrolled farms are similar to the target population of dairy farms in Alberta and can therefore be extrapolated to whole Alberta. The range of herd sizes was with a minimum of 60 to a maximum of 293 lactating cows per farm large. Eleven farms had a herd that was smaller than 150 lactating cows and 2 farms had a herd with more than 150 cows. Consequently, less measurements of larger herds were included compared with smaller herds. For that reason it is not possible to draw conclusions from the eventual correlation between herd size and antimicrobial usage. Young stock was not included in the herd sizes for this report. Therefore, the measured antimicrobial use per cow per year is higher than the real use, because the products in the garbage can included the products that were used for the young stock as well. The products that were collected are not completely accurate because farmers or their employees sometimes forgot to put used products in the garbage can, or did not know which used product they should put in the garbage can during the first month of the audit. Some products are therefore excluded for one month, but not all products. Hence it is very unlikely that a considerable part of the antimicrobial use data is lost during that period or for the total project. The use of medicated feed (that contained monensin) that was measured during this project was 0.012 grams per cow per year. Probably feed medicated with monensin was not used for lactating cows, but for the calves because you cannot deliver milk of cows treated with 11 Antimicrobial use on dairy farms in Alberta S.H. Bruil monensin in Canada. It is not clear if other farms used medicated feed as well and if they used it, which products these used and in what quantity. All data should become clearer when the results from the CBMRN are published. There is unfortunately not enough data available yet to interpret the outcomes significantly. ACKNOWLEDGEMENTS I would like to thank Dr. Herman Barkema and Dr. Ruurd Jorritsma for supervising me during the research project and giving me the opportunity to participate in the CBMRN and to visit Canada. In addition, I would like to thank Anke Wellen, Vineet Saini, Sharon Schille, Simon Dufour, Karin Orsel, Frank van der Meer, Jos van Embden, Carlijn Wauben and Bregje Witlox for their help and support. 12 Antimicrobial use on dairy farms in Alberta S.H. Bruil REFERENCES Bogaard A.E. van den, Stobberingh E.E, 2000. Epidemiology of resistance to antibiotics, Links between animals and humans. International Journal of Antimicrobial Agents 14, 327– 335 Bywater R.J., Casewell M.W., 2000. An assessment of the impact of antibiotic resistance in different bacterial species and the possible contribution of animals to resistance in human infections. Journal of Antimicrobial Chemotherapy 46, 643–645. Canadian Bovine Mastitis Research Network (CBMRN). National Cohort Reference Manual, version 10.9.07. Government of Canada, 2007. Canadian Integrated Program for Antimicrobial Resistance Surveillance 2005(CIPARS). http://www.phac-aspc.gc.ca/cipars-picra/index.html, ISBN: 9780-662-46095-4. Gustafson R.H., Bowen R.E., 1997. Antibiotic use in animal agriculture. Journal of Applied Microbiology 83, 531–541. Health Canada, 2002. Uses of Antimicrobials in Food Animals in Canada: Impact on Resistance and Human Health. Prepared for: Veterinary Drugs Directorate. www.hc-sc.gc.ca. McEwen S.A., Fedorka-Cray P.J., 2002. Antimicrobial Use and Resistance in Animals. Clinical Infectious Diseases 34, (Suppl 3) 93–106. Schwarz S., Chaslus-Dancla E., 2001. Use of antimicrobials in veterinary medicine and mechanisms of resistance. Veterinary Research 32, 201-225. Schwarz S., Kehrenberg C., Walsh T.R., 2001. Use of antimicrobial agents in veterinary medicine and food animal production. International Journal of Antimicrobial Agents 17, 431– 437. Sischo W.M., 2001. Stakeholder position paper: Dairy producer. Preventive Veterinary Medicine 73, 203–208. Teuber M., 2001. Veterinary use and antibiotic resistance. Current Opinion in Microbiology 4, 493-499. World Health Organization (WHO). Global Strategy for Containment of Antimicrobial Resistance. WHO/CDS/CSR/DRS/2001.2 Websites: (PHAC) Public Health Agency of Canada. www.phac-aspc.gc.ca (CVI) Centraal Veterinair Instituut. www.cvi.wur.nl Alberta Milk. www.albertamilk.com 13