Use of antimicrobials in dairy farming

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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
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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
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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.
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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).
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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
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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.
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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.
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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
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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
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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 #
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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
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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.
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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
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