While it may not be possible to solve the antibiotic resistance issue, it is possible to stop talking past the issue and work co-operatively to forge a way forward. Dr. Lonnie King, dean, Ohio State College of Veterinary Medicine in his keynote address to the National Institute of Animal Agriculture (NIAA), November 2014, was confident much could be done over the next five years. His thoughts on what could be reasonably accomplished:
- Build a portfolio of mutual interest and turn that into a national strategy and a national plan.
- Make sure all groups involved are also part of the solution, so nobody’s left out.
- Help the public and decision makers better understand this issue and not take sides as we look for a solution.
- Adopt a stewardship plan across the board.
Ensure agriculture is helping lead the way and seen as such. In order to address antibiotic stewardship in human and animal practice, careful and accountable use of antibiotics in all settings is necessary. To this end, ensuring disease prevention takes precedence over the existing dependence on antibiotics is critical. Investment in development and use of vaccines is an important corollary. Increased veterinary oversight regarding use of antimicrobials in livestock production can be an important step forward if genuinely accepted and staunchly observed in all circumstances. Veterinary oversight of antimicrobial use must go hand-in-hand with veterinary guidance to industry on implementation of optimal production rearing practices that minimize disease. Development and use of rapid diagnostics will play a role. Development of educational programs for doctors, patients, veterinarians and clients is essential. Educational opportunities need to be accessible to a broad spectrum of users and part of patient/client stewardship programs with a One Health perspective. One Health perspectives will only evolve if understood and endorsed by all players.
Major progress depends on decreasing antibiotic use, not the complete explanation of resistance and mechanisms behind resistance. More investment is needed in finding ways to measure antibiotic use, incidents of resistance, use patterns and outcomes. The shift of priorities from pure academic research to metrics and surveillance is critically important.
Metrics of success in the effort to mini- mize the development of antibiotic resistance include assessing the effectiveness of antibiotic stewardship programs, increasing veterinary oversight in animal agriculture, and more careful monitoring of antibiotic usage and resistance in human and animal health.
A report to President Obama on combating antibiotic resistance from the President’s Council of Advisors on Science and Technology (PCAST) in September 2014 stated, “While it is clear that agricultural use of antibiotics can affect human health, what is less clear is its relative contribution to antibiotic resistance in humans compared to inappropriate or overuse in health care settings. This uncertainty is largely due to difficulties in tracing precisely the origins and spread of specific resistant microbes and, more fundamentally, the transmission and spread of specific resistance genes in microbial communities. It also reflects a gap in our understanding of the complexity of resistance across different species and the environment.” This report also notes the diversity of livestock operations, assesses the impact of changes, and calls for national capability for microbial surveillance in humans and agriculture. The report’s comment about animal agriculture, “… [the] extent to which antibiotic resistance in animal agriculture contributes to human infection is not known [and] risks to human health posed by the agricultural use of antibiotics are, appropriately, a matter of serious concern.”
Unlike the human medical community, veterinarians often manage as their own pharmacies. In doing so veterinarians put themselves in the role of diagnosticians, pharmacy owners and prescribers. Drug sales are part of most food animal business plans, a practice coming under increased public scrutiny and one that potentially contrasts with sound antibiotic stewardship and prudent use.
A positive step forward in antibiotic stewardship has been the evolution of quality assurance programs in animal agriculture. Quality assurance guidelines are implicit about eliminating drug residues in food products and provide important direction toward enhanced antibiotic stewardship.
The fundamentals of a national strategy — in both Canada and the U.S. — for combating antibiotic resistance have been discussed for two decades and gathered into various briefs, synopses and reports, yet little new comes forth from abstracts submitted to those who commission input. The missing piece always seems to be commitment to invest in change that will make a difference. It seems everyone awaits the miracle of change without inducing change. Few can argue that the level of understanding about what is needed to slow the spread of antibiotic-resistant bacteria is at hand. A resolute and courageous step forward must replace the erratic and checkered dance around AMR that has marked the past 20 years.
Guidance for Industry #213, published in 2012 by the Food and Drug Administration in the U.S., is one of the first new initiatives that will move the North American industry toward a level of stewardship we have col- lectively talked about for years, yet have been afraid to take the step. Not that many years ago, Guidance #213 would have encountered sulphurous resistance by various industry factions. Today, the opposition offered to a game-changing piece of regulatory reform is cautious, but clearly shows industry’s accession of the move against AMR was inevitable and predetermined. Almost certainly, Canada will be forced to follow suit.
Guidance #213 provides impetus to phase out use of medically important antimicrobials in food animals for production purposes (e.g. to enhance growth or improve feed efficiency), and to bring the therapeutic uses of such drugs (to treat, control, or prevent specific diseases) under the oversight of licensed veterinarians. Against the backdrop of advances in the U.S., Canada continues to struggle with loopholes in federal regulations that allow the import of Active Pharmaceutical Ingredients (APIs) — antibiotics in their raw chemical form, many from third-rate manufacturing facilities in China, India and Eastern Europe. Access to APIs from approved manufacturing facilities allows legitimate manufacturing companies to import raw product for pre-approval manufacturing and testing. Drug regulations were never intended to allow producers the ability to import and incorporate APIs into livestock feed for therapeutic and growth promotion purposes, a serious and unjustifiable blemish on Canada’s prudent use of drugs.
A second flaw in Canadian regulations is the rule allowing producers to import non-approved vaccines and pharmaceuticals for their own use. Own Use Import (OUI) guidelines, initially struck to facilitate import of vaccines and drugs from the U.S. not yet approved in Canada in the case of disease outbreaks. Typically, drugs imported under OUI concessions did not have analogous counterparts in Canada and none carry Canadian drug identifica- tion numbers (DIN) — numbers assigned to all approved drugs. Today’s economic climate and exchange rates shifted and expanded producer use of OUI concessions to include a wider range of livestock drugs. Although importers provide sworn affidavits to customs at border crossings regarding the fact that drugs are to be used in their own herds and that veterinary prescriptions are issued for drugs requiring prescriptions, inconsistencies occur that seem to fly in the face of prudent drug use and redeeming stewardship.
In 1997, calls for surveillance of AMR and antimicrobial use in Canada were published, with the recommendation to establish a national farm surveillance system to monitor AMR and use in the agri-food and aquaculture sectors. As a result, the Canadian Integrated Program for Antimicrobial Resistance Surveillance (CIPARS) was established, and co-ordinated by the Public Health Agency of Canada in partnership from Veterinary Drugs Directorate, Health Canada; Canadian Food Inspection Agency; Agriculture and Agri-Food Canada; Provincial agriculture and public health academia; and private industry. The objectives of the CIPARS Farm Program include establishing an infrastructure to support a national farm surveillance program that collects AMR and use data, describes trends in farm use and AMR, investigates the association between farm antimicrobial use and resistance, and provides sound data for human health risk assessments.
As we move toward a more effective, responsible and action-oriented approach to AMR, other factors come into play:
- Understanding the role of irradiation of food products in preventing foodborne pathogen infections, but also for antimicrobial resistance from foodborne pathogens to humans.
- Identify control points that can restrict the transfer via food, soil, and water of antibiotic-resistant bacteria from agricultural settings.
- New antibiotic development. The need for new antibiotics is so urgent government officials, drug companies and medical experts, faced with outbreaks of antibiotic-resistant “superbugs,” are pushing to speed up the approval of new antibiotics, a move raising safety concerns among some critics.
- Non-antibiotic interventions to combat bacterial diseases.
- Government funding directly to pharmaceutical companies to initiate antibiotic development. Pharmaceutical companies frequently choose to put resources into drug development with bigger payoffs.
- Manipulation of the immune system to enhance its effectiveness during bacterial invasion.
- Corporate-induced cuts to antibiotic use by the production industry.
The time for talk has passed. We are on a fast track backward to a pre-antibiotic era when infectious diseases were the leading cause of death. One author described it as sleepwalking toward a third-world status; another described the AMR dilemma a “tragedy of commons” where perceived, potential self-benefit is weighed against a small potential harm to society at large.
The use of antibiotics is the single most important factor leading to antibiotic resistance, and the single most important action needed is to reduce their use. If co-operation can’t be fostered among all key stakeholders, a post-antibiotic era is inevitable.
Tipping the balance requires a wholesale change in attitude. North Dakota Department of Health’s Dr. Terry Dwelle, a pediatrician and rancher, boiled it down to being vigilant, judicious and smart. Most importantly we need to come out from behind the barricades and silos and work together (November 2013, National Institute for Animal Agriculture, Bridging the Gap between Animal Health and Human Health).
Having achieved a greater awareness of the threat of antibiotic resistance, it may be time for a switch to education; move it to the trenches, to the moment of contact and decision-making. We can do better.