Food Safety and the Diminishing Arsenal of Antibiotics Dr. Rebecca Irwin, DVM, MSc. Coordinator, Antimicrobial Resistance Unit Laboratory for Foodborne Zoonoses Health Canada Guelph, Ontario

Human cases of antimicrobial-resistant infections are rising dramatically. Of particular concern are those infections acquired in hospitals such as Vancomycin-resistant enterococci (VRE) or Methicillin-resistant Staphylococcus Aureus (MRSA). Among community-acquired infections, concerns are rising with the increasing prevalence of MRSA, Penicillin-resistant Streptococcus Pneumonia, multi-drug resistant (MDR) tuberculosis, and in enteric infections such as MDR Salmonella Typhimurium DT104, MDR Salmonella Newport, and Fluoroquinolone-resistant Campylobacter spp.

The medical consequences arising from the development of antimicrobial resistance in bacterial pathogens include treatment failures, increased drug costs (for 2nd and 3rd line drugs), increased length of hospitalization, increased infection control costs, and increased laboratory costs. A further complicating issue is the lack of development of new classes of antimicrobials. The pharmaceutical industry is reluctant to invest millions of dollars in research and development for what is considered a fairly small return on investment. As a result of this the call for action rests with ensuring the useful life of existing products and to promote the development of prudent use policies.

Antimicrobial use in food animals has been the subject of much controversy over the past 40 years. The subject of antimicrobial use and its contribution to resistance in human pathogens has been the subject of discussion at many meetings, conferences and expert deliberations. Historically, as quoted by the 1995 report from US Office of Technology Assessment údirect evidence ... that shows a direct connection between agricultural use of antibiotics and human illness and death is sparse and difficult to obtainî. However, recent data emerging from surveillance programs in the U.S. and Denmark is providing the evidence that the use of antimicrobials in all sectors (animal, human, plant, etc.) is contributing to the overall burden of antimicrobial resistance.

Internationally there are many initiatives underway to address antimicrobial resistance. Leading the initiatives on a global scale is the World Health Organization. The WHO has recently published a document entitled úGlobal Principles for the Containment of Antimicrobial Resistance in Animals Intended for Foodî. This document is part of a larger global strategy published by the WHO which sets out 64 recommendations for the containment of antimicrobial resistance.

The OIE (Office International des Epizooties) has also established antimicrobial resistance as one of its priorities for coming years. In conjunction with an extensive consultation process, the OIE has published five guidelines on the topics of risk analysis, prudent use, antimicrobial use, antimicrobial resistance surveillance, and laboratory methodology. They are also working closely with various CODEX alimentarius groups working on the AMR issue.

Many countries are developing prudent use guidelines for major food animal species for application by veterinarians and producers. As an example, the Canadian Veterinary Medical Association has published Prudent-Use Principles which are comprehensive and consistent with those from other countries. These principles are essentially voluntary and a system to monitor their effectiveness is currently unavailable. Many factors exist that will determine their implementation among veterinarians and producers. Factors such as: awareness of resistance issues; desire to prolong the useful lifespan of antimicrobials; willingness to modify prescribing behaviours and treatment practices; cost, efficacy and availability of alternatives; and incentives for the prescription and sale of antimicrobials. As part of their annual convention in 2002, the CVMA held a symposium where the subject of prudent use of antimicrobials was discussed extensively.

Market forces are driving the implementation of On-Farm Quality Assurance programs. Most commodity groups have, or are in the process of developing these programs.

Although On-Farm Food Safety Programs are mostly geared to residue avoidance and do not yet specifically seek to control antimicrobial resistance on the farm, these programs do promote elements of prudent antimicrobial use. Recent press has indicated that some of the larger multi-national fast food corporations are requiring their suppliers to provide product that has not been exposed to growth promotion antimicrobials.

In Canada, antimicrobial resistance (AMR) in major human pathogens and in enteric pathogens such as Salmonella and Shigella appears to be increasing, impacting on health care costs and therapeutic options. In May 1997, a national consensus conference entitled úControlling Antimicrobial Resistance: An Integrated Action Plan for Canadiansî was co-convened by Health Canada and the Canadian Infectious Diseases Society. Several recommendations arose from this conference, including the need to establish a national surveillance system to monitor antimicrobial resistance and use in the agri-food and agriculture sectors and the impact of resistance on human health. Health Canada has taken steps to action a number of recommendations from the conference with the ultimate goal to develop key strategies to track usage of antimicrobials, and to control the emergence and spread of AMR from livestock and aquaculture sources.

Identifying the magnitude of the resistance problem in Canada is hampered by the lack of an ongoing, representative, active or passive resistance surveillance system. Available data on resistance in bacteria derived from food animals is highly fragmented and drawn from a few regions and targeted studies. Health Canada's Laboratory for Foodborne Zoonoses (LFZ) has been tasked with developing a national integrated surveillance program for antimicrobial use and antimicrobial resistance in agri-food and aquaculture.

An integrated strategy has been developed which includes both human and animal components.

The Veterinary Drugs Directorate (VDD) of Health Canada has recently assumed the lead for the development of antimicrobial resistance policies associated with the use of antimicrobials in the agri-food and aquaculture sectors. In January 2002, the VDD established the Interdepartmental Policy Committee on AMR to develop Canadian policies to address the emergence and spread of antimicrobial resistance. This committee is comprised of representatives of Health Canada, Environment Canada, the Canadian Food Inspection Agency and the Department of Fisheries and Oceans. A major input to policy discussions is the recent report of the Advisory Committee on Animal Uses of Antimicrobials and Impact on Resistance and Human Health. This expert advisory committee was formed in December 1999 to assist Health Canada in the development of antimicrobial use policies, surveillance and research related to the use of antimicrobial drugs in food-producing animals. The final report from this committee was presented to Health Canada in June, 2002. Copies of this report are available on the Health Canada website at
http://www.hc-sc.gc.ca/vetdrugs-medsvet/amr/e_policy_dev.html#AMRReport

Another important input to the policy deliberations will be the outcome of the Canadian Committee on Antibiotic Resistance (CCAR) national policy conference being held October 6-7, 2002 in Aylmer, Quebec. This conference is designed to develop consensus on specific strategies to be addressed in a national action plan to combat antibiotic resistance in Canada. Health Canada will be working with CCAR to further develop the action plan.