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Editorial

Farm-grown superbugs: While the world acts, Canada dawdles

Barbara Sibbald
CMAJ October 02, 2012 184 (14) 1553; DOI: https://doi.org/10.1503/cmaj.120561
Barbara Sibbald
Barbara Sibbald is Deputy Editor, Analysis and Humanities, CMAJ.
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  • Superbugs and the agricultural industry
    Hugh G. Whitney
    Posted on: 30 November 2012
  • Regarding use of antimicrobials in food animals in Canada
    David N. Fisman
    Posted on: 18 October 2012
  • Farm-grown superbugs
    Brad Hicks
    Posted on: 02 August 2012
  • Farm-grown superbugs editorial
    John F. Prescott
    Posted on: 21 June 2012
  • CMAJ Editorial Response
    Duane C Landals
    Posted on: 21 June 2012
  • Letter to the Editor of the CMAJ in response to the June 4, 2012 CMAJ editorial by Barbara Sibbald BJ
    Brian R. Radke
    Posted on: 21 June 2012
  • Posted on: (30 November 2012)
    Page navigation anchor for Superbugs and the agricultural industry
    Superbugs and the agricultural industry
    • Hugh G. Whitney, Chief Veterinary Officer

    I have just seen a copy of the October 2nd, 2012 editorial by Barbara Sibbald on superbugs and her conclusion that the agricultural industry is primarily responsible for this phenomenon. Not being an expert on this issue I will avoid generalizations on responsibility but would encourage your readers to look up reviews on the subject including presentations given at a 2011 forum on this issue available on the web at antim...

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    I have just seen a copy of the October 2nd, 2012 editorial by Barbara Sibbald on superbugs and her conclusion that the agricultural industry is primarily responsible for this phenomenon. Not being an expert on this issue I will avoid generalizations on responsibility but would encourage your readers to look up reviews on the subject including presentations given at a 2011 forum on this issue available on the web at antimicrobialcanada.com.

    I would like to correct though the statement that only the Province of Quebec has taken a legal stand on antimicrobial use in the agricultural industry. In the Province of Newfoundland and Labrador, it is illegal to sell directly to a consumer an antibiotic for animal use, that is in a form for injection or oral, intramammary or intrauterine administration, unless the sale is made under a prescription by a veterinarian. The sole exemption is if the antibiotic is used in conformity with the federal Feeds Act.

    I presume that the intent of the editorial was to generate debate, I'm sure it will.

    Thank you.

    Dr. Hugh Whitney

    Conflict of Interest:

    None declared

    Show Less
    Competing Interests: None declared.
  • Posted on: (18 October 2012)
    Page navigation anchor for Regarding use of antimicrobials in food animals in Canada
    Regarding use of antimicrobials in food animals in Canada
    • David N. Fisman, Associate Professor

    I wish to write to applaud Barbara Sibbald for her short article on the human health implications of antimicrobials in agriculture (1). I was interested to learn about the degree to which Canada has lagged behind other countries in regulating their use. I wished to write on two points of clarification: the first relates to a statement made in the article about quinpristin-dalfopristin as the "...quinupristin-dalfopristi...

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    I wish to write to applaud Barbara Sibbald for her short article on the human health implications of antimicrobials in agriculture (1). I was interested to learn about the degree to which Canada has lagged behind other countries in regulating their use. I wished to write on two points of clarification: the first relates to a statement made in the article about quinpristin-dalfopristin as the "...quinupristin-dalfopristin, [is] our last line of defence if Staphylococcus aureus or Enterococcus infections develop resistance to vancomycin"(1). The second relates to additional sources of concern regarding the potential infectious disease consequences of heavy antimicrobial use in agriculture.

    With respect to the article's statement regarding S. aureus and Enterococcus sp., I would note that vancomycin-resistant Enterococcus (VRE) has been recognized for over two decades (2);strains of S. aureus with intermediate-level resistance to vancomycin were described in 1997 (3), and high-level vancomycin resistant S. aureus was described (outside the laboratory) in 2002 (4). The role that agricultural use of avoparcin played in the genesis of VRE in humans is controversial, but recognition of the potential links between avoparcin and VRE likely contributed to European decisions to remove this antibiotic from feeds, as mentioned in the article (5). Fortunately, however, quinpristin-dalfopristin is not the only agent with activity against multiresistant gram positive microbes. Daptomycin and linezolid are available in Canada, and other agents (such as ceftaroline) have been approved in the U.S. and await approval in Canada.

    The article did not mention multi-drug resistant gram negative pathogens, including Acinetobacter species, Pseudomonas aeruginosa, and the Enterobacteraceae (including recently described strains with a novel plasmid-borne carbapenemase (6)), some of which have actually reached a point of being effectively pan-resistant to available antimicrobials (7). Such microbes are environmentally abundant, in agricultural runoff, surface waters, and sewage, and (particularly given the tendency of resistance determinants to cluster at the microbial level) the environmental contamination associated with agricultural antibiotic use provides a source of selective pressure that gives a competitive advantage to resistant microbes.

    An additional, but more controversial, reason for concern around antimicrobial use in agriculture relates to verotoxigenic strains of E. coli, which are (at the time of writing) the source of a massive meat recall, and numerous cases of enteric illness, in Canada (8). There is (limited) evidence suggesting that the use of antibiotics and other growth promoters as linked to carriage of VTEC strains like E. coli O157:H7 (9), and if this relationship is proved may provide additional support for the restriction of antimicrobial use in food animals. I hope that the above serves to underscore the importance and timeliness of this article. Again, I write to express my gratitude to Ms. Sibbald for having written the article, and to the CMAJ for giving this issue the prominence it deserves.

    Sincerely,

    David N. Fisman, MD MPH FRCPC Associate Professor of Public Health (Epidemiology) Dalla Lana School of Public Health University of Toronto

    References

    1. Sibbald B. Farm-grown superbugs: While the world acts, Canada dawdles. CMAJ. 2012 Oct 2;184(14):1553.

    2. Gold HS, Unal S, Cercenado E, Thauvin-Eliopoulos C, Eliopoulos GM, Wennersten CB, et al. A gene conferring resistance to vancomycin but not teicoplanin in isolates of Enterococcus faecalis and Enterococcus faecium demonstrates homology with vanB, vanA, and vanC genes of enterococci. Antimicrob Agents Chemother. 1993 Aug;37(8):1604-9.

    3. Smith TL, Pearson ML, Wilcox KR, Cruz C, Lancaster MV, Robinson- Dunn B, et al. Emergence of vancomycin resistance in Staphylococcus aureus. Glycopeptide-Intermediate Staphylococcus aureus Working Group. N Engl J Med. 1999 Feb 18;340(7):493-501.

    4. Chang S, Sievert DM, Hageman JC, Boulton ML, Tenover FC, Downes FP, et al. Infection with vancomycin-resistant Staphylococcus aureus containing the vanA resistance gene. N Engl J Med. 2003 Apr 3;348(14):1342 -7.

    5. Bonten MJ, Willems R, Weinstein RA. Vancomycin-resistant enterococci: why are they here, and where do they come from? Lancet Infect Dis. 2001 Dec;1(5):314-25.

    6. Kumarasamy KK, Toleman MA, Walsh TR, Bagaria J, Butt F, Balakrishnan R, et al. Emergence of a new antibiotic resistance mechanism in India, Pakistan, and the UK: a molecular, biological, and epidemiological study. Lancet Infect Dis. 2010 Sep;10(9):597-602.

    7. Walsh TR, Toleman MA. The emergence of pan-resistant Gram-negative pathogens merits a rapid global political response. J Antimicrob Chemother. 2012 Jan;67(1):1-3.

    8. Public Health Agency of Canada. Public Health Notice: E coli O157 illness related to beef. Available via the Internet at http://www.phac- aspc.gc.ca/fs-sa/phn-asp/ecoli-1012-eng.php. Last accessed October 15, 2012. Ottawa, Ontario, Canada2012 [updated October 12, 2012.].

    9. Lefebvre B, Diarra MS, Giguere K, Roy G, Michaud S, Malouin F. Antibiotic resistance and hypermutability of Escherichia coli O157 from feedlot cattle treated with growth-promoting agents. J Food Prot. 2005 Nov;68(11):2411-9.

    Conflict of Interest:

    None declared

    Show Less
    Competing Interests: None declared.
  • Posted on: (2 August 2012)
    Page navigation anchor for Farm-grown superbugs
    Farm-grown superbugs
    • Brad Hicks, Feed Manufacture

    Interesting editorial, lots of threats about the use of antibiotics in animals leading to antibiotic resistance in man. However, despite the ban on the growth promotion use of antibiotics in Sweden for many years and more recently Denmark and the EU in general, no evidence is presented that these bans are having any influence on the amount of animal derived antibiotic resistance in man only that the ban has resulted in a...

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    Interesting editorial, lots of threats about the use of antibiotics in animals leading to antibiotic resistance in man. However, despite the ban on the growth promotion use of antibiotics in Sweden for many years and more recently Denmark and the EU in general, no evidence is presented that these bans are having any influence on the amount of animal derived antibiotic resistance in man only that the ban has resulted in an increase in the cost of food. The author presents no hard support for the thesis that widespread antibiotic bans in animals have any widespread beneficial effects for human health.

    The value of this debate would improve if there was a real effort to quantify the actual benefits of more restrictive policies on antibiotic use in animals, rather than speculative assumptions. Having followed this debate for the past 40 years, it appears to me that the agriculture industry is more of a scapegoat for poor medical practitioner practices that poor agriculture practices. This debate will have to get beyond, no mea culpa, if truly effective policies are to be developed.

    Conflict of Interest:

    None declared

    Show Less
    Competing Interests: None declared.
  • Posted on: (21 June 2012)
    Page navigation anchor for Farm-grown superbugs editorial
    Farm-grown superbugs editorial
    • John F. Prescott, Professor
    • Other Contributors:

    As members of the Ad Hoc Committee for Antimicrobial Stewardship in Canadian Agriculture and Veterinary Medicine we would like to comment on your editorial on "farm grown superbugs".

    The purpose of our Committee is to press for outcomes to the action points identified at the 2011 Conference in Toronto on "Antimicrobial Stewardship in Canadian Agriculture and Veterinary Medicine: How is Canada doing and what sti...

    Show More

    As members of the Ad Hoc Committee for Antimicrobial Stewardship in Canadian Agriculture and Veterinary Medicine we would like to comment on your editorial on "farm grown superbugs".

    The purpose of our Committee is to press for outcomes to the action points identified at the 2011 Conference in Toronto on "Antimicrobial Stewardship in Canadian Agriculture and Veterinary Medicine: How is Canada doing and what still needs to be done?" A report of the conference (Canadian Veterinary Journal 2012; 53: 402-407) will soon be freely downloadable through PubMed.

    There are some clear misunderstandings of antimicrobial use in animals in Canada in the editorial. We also disagree with your perspectives and characterizations of agricultural practices, which represent an uninformed and stereotypic view of a critically important industry globally. In the spirit of the term 'One Health", we do support your call for regulatory reform in the area of antibiotic use in animals, to bring Canada into line with international standards as detailed in World Health Organization documents on the topic (e.g., Global strategy for containment of antimicrobial resistance, 2001; The evolving threat of antimicrobial resistance, 2012). Beyond this action it is important that human and animal health continue to work together to preserve the critically important medications needed to manage disease in the future.

    The regulation of antimicrobial drug use in Canada, particularly regulations around own use importation, active pharmaceutical ingredient use, and extra-label use, is by far Canada's weakest link in managing antibiotic stewardship in agriculture and veterinary medicine. As you note in the editorial, the issue is that the federal government through Health Canada regulates the pre-market assessment and licensing of antibiotics for sale while the actual use of antibiotics is controlled at the provincial level. This leaves a major gap in the framework by which animal use of antibiotics is managed, a problem that needs to be addressed seriously, and with urgency.

    The committee therefore suggests that the following measures relating to regulation in animals be implemented expeditiously: Removing of the "own use importation" and "active pharmaceutical ingredient importation" loopholes in the regulations, since there is no Canadian quality or safety risk assessment involved with these products; the ability under appropriate circumstances to ban nationally the extra-label use of certain antibiotics.

    We should not have to wait for a crisis in antimicrobial resistance to make the regulatory changes that are so clearly needed. What is needed in Canada is political leadership towards judicious antimicrobial use policy.

    Yours sincerely,

    John Prescott, Department of Pathobiology, University of Guelph

    Jean Szkotnicki, Canadian Animal Health Institute, Guelph

    Conflict of Interest:

    None declared

    Show Less
    Competing Interests: None declared.
  • Posted on: (21 June 2012)
    Page navigation anchor for CMAJ Editorial Response
    CMAJ Editorial Response
    • Duane C Landals, Registrar

    The Alberta Veterinary Medical Association (ABVMA) is the professional regulatory organization responsible for the practice of veterinary medicine in Alberta, under the authority of the Veterinary Profession Act. Veterinarians registered under this act are medical practitioners with the authority to prescribe medications for the treatment of animals. Like our colleagues in the human health field, we are acutely aware of...

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    The Alberta Veterinary Medical Association (ABVMA) is the professional regulatory organization responsible for the practice of veterinary medicine in Alberta, under the authority of the Veterinary Profession Act. Veterinarians registered under this act are medical practitioners with the authority to prescribe medications for the treatment of animals. Like our colleagues in the human health field, we are acutely aware of the hazards posed by the use of antimicrobial drugs. We believe every effort must be taken to maintain the utility and safety of these products both for animal and human health. The ABVMA is partnering with animal industry stakeholders in an effort to increase awareness in all sectors of the need for appropriate stewardship of this essential commodity. We have launched a program called Alberta Platform for the Responsible Use of Medications in Animals (APRUMA) and have developed a site to exchange information on this topic www.apruma.ca.

    While we applaud the effect Barbara Sibbald, Deputy Editor, has had in stimulating awareness of this timely topic, we believe the published editorial also highlights some common areas of confusion. Certain antimicrobials can be and are used in animal agriculture in both a preventative and growth promoting capacity. These are not the same purpose, although one might support the other. In reality, both of these uses are in accordance with existing drug label claims as approved by Health Canada, and therefore should not be confused with "off label use". When used according to label, however, these antimicrobials do not require a prescription from a veterinarian and consequently professional supervision might be lacking.

    The writer is correct in stating that the practice of veterinary medicine is regulated provincially. The classification of pharmaceuticals as either prescription only or non-prescription, however, is the federal responsibility of Health Canada. A drug classified as non-prescription is available for over the counter sales for use in animals. These then fall outside of the scope of regulated veterinary practice.

    While appreciating the writers' assertion that improved agricultural practices can contribute to safer use of antimicrobials, I believe it might be more correct to say that improved standards of animal production and hygiene might lead to improved animal welfare and reduced use of antimicrobials. There is real concern that restriction of appropriate antimicrobial use might actually lead to animal welfare concerns. This apparently has been seen in other jurisdictions.

    My final reservation comes from the reference to the total percentage volume of antimicrobials used in animals versus human health. These numbers are seemingly meaningless unless the biomass of patients treated is considered. These numbers are commonly discussed and I am not certain anyone has the best solution of how to report and compare volume of antimicrobial use.

    Despite these reservations, I think the editorial is successful in once again raising the signal flag that our processes need to continually be reviewed and updated where necessary.

    Sincerely,

    Dr. Duane Landals BSc. Ag., DVM Registrar, Alberta Veterinary Medical Association Vice President, World Veterinary Association

    Conflict of Interest:

    None declared

    Show Less
    Competing Interests: None declared.
  • Posted on: (21 June 2012)
    Page navigation anchor for Letter to the Editor of the CMAJ in response to the June 4, 2012 CMAJ editorial by Barbara Sibbald BJ
    Letter to the Editor of the CMAJ in response to the June 4, 2012 CMAJ editorial by Barbara Sibbald BJ
    • Brian R. Radke, Public Health Veterinarian
    • Other Contributors:

    After reading the journal's "Farm Grown Superbugs" editorial of June 4, 2012, we suggest that CMAJ could better engage food producers and provide more accurate information in collaboration with veterinary colleagues.

    Use of antibiotics for disease prevention and growth promotion is not off-label. Federal legislation regulates the sale and use of drugs in livestock feeds and the Canadian Food Inspection Agency...

    Show More

    After reading the journal's "Farm Grown Superbugs" editorial of June 4, 2012, we suggest that CMAJ could better engage food producers and provide more accurate information in collaboration with veterinary colleagues.

    Use of antibiotics for disease prevention and growth promotion is not off-label. Federal legislation regulates the sale and use of drugs in livestock feeds and the Canadian Food Inspection Agency monitors those medicating ingredients permitted by Canadian regulation to be added to feed. A veterinary prescription is required for medicated feed that does not meet the federal legislation.

    Care is required in comparing gross antimicrobial use estimates between humans and animals. The population of Canadian terrestrial livestock is approximately twenty times that of the human population, however, antimicrobial usage per population mass is the preferred metric for comparison. Note the CIPAR's animal data1 includes use for all animal species, not just livestock, and the CIPARS human use data excludes hospital pharmacy data. In 2007, over 25% of the antimicrobials distributed for animals were antibiotic classes not used in humans (Health Canada category IV antimicrobials). We agree with the need to supplement existing data1, 2 on antibiotic usage in animals, and a number of efforts are underway. However, without a veterinary equivalent to the Canadian CompuScript program, collecting this information is difficult.

    The editorial mentions a number of policy options for regulating antibiotic use in animals. There is a lack of consensus on the strength of the evidence for the options. For an airing of the different opinions on the evidence associated with growth promotant bans see Phillips et al. and associated letters to editor. The sufficiency of reductions in antibiotic resistance in animal associated bacteria as evidence of improvement in human health is contentious.

    Although intuitively appealing, we are unaware of any evidence that restricting livestock antibiotics to prescription use impacts levels of antimicrobial resistance in animal associated bacteria, or human pathogens. Casual review of the CIPARS data1 suggests the level of antibiotic resistance in Quebec raw retail meat bacteria is similar to other provinces where prescriptions are not necessarily required for veterinary antibiotics. There are a number of possible explanations for this including that producers, regardless of where they purchase the antibiotics, are similarly using the products.

    Estimates or evidence of the human health benefits of policy options are beneficial to weigh against the potential negative or unintended consequences of policy decisions. For example, following the European ban of growth promotants, although overall antibiotic use decreased, therapeutic use increased3. Requiring veterinary prescriptions for antibiotics could negatively impact animal welfare especially for producers without convenient access to veterinarians, or producers with small numbers or low value livestock.

    We agree policy options can impact the cost of food, and the affordability of food, particularly for those with low income, is increasingly becoming a societal concern.

    The "Antimicrobial Stewardship in Canadian Agriculture and Veterinary Medicine: How is Canada doing and what still needs to be done?" conference was held in November 2011. The importance of antibiotic stewardship and collaboration among all users of antibiotics were major themes. We appreciate the interest of the human medical professions in antibiotic use in animals and look forward to future collaborative efforts.

    Brian Radke DVM, PhD Public Health Veterinarian

    Paul Kitching BVetMed, PhD Chief Provincial Veterinarian

    Jane Pritchard BA, DVM, MVetSc Manager Livestock Health Management and Regulation

    Nancy de With DVM, MSc Veterinary Epidemiologist

    Bill Cox DVM, Dip. Path Poultry Health Veterinarian

    References

    1) CIPARS 2007 -- final report. Ottawa (ON) and Winnipeg (MB): The Public Health Agency Canada; modified 2010. Available: www.phac-aspc.gc.ca/cipars -picra/2007_2-eng.php (accessed 2012 June 12)

    2) BC Ministry of Agriculture. Therapeutantic (antibiotic) use in aquaculture http://www.agf.gov.bc.ca/ahc/fish_health/antibiotics.htm (accessed 2012 June 12)

    3) Phillips et al. Does the use of antibiotics in food animals pose a risk to human health? A critical review of published data. J Antimicrob Chemother 2004;53:28-52. Available: http://jac.oxfordjournals.org/content/53/1/28.full.pdf+html (accessed 2012 June 12).

    Conflict of Interest:

    None declared

    Show Less
    Competing Interests: None declared.
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Farm-grown superbugs: While the world acts, Canada dawdles
Barbara Sibbald
CMAJ Oct 2012, 184 (14) 1553; DOI: 10.1503/cmaj.120561

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Farm-grown superbugs: While the world acts, Canada dawdles
Barbara Sibbald
CMAJ Oct 2012, 184 (14) 1553; DOI: 10.1503/cmaj.120561
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