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Institute of Medicine (US). Improving Food Safety Through a One Health Approach: Workshop Summary. Washington (DC): National Academies Press (US); 2012.

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Improving Food Safety Through a One Health Approach: Workshop Summary.

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A15ANTIBIOTIC RESISTANCE—LINKING HUMAN AND ANIMAL HEALTH

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This paper will address the transmission of antibiotic-resistant microorganisms between animals and humans in a One Health perspective. It will give a general introduction to the epidemiology of antibiotic resistance in zoonotic pathogens and then focus on some national and international programs for integrated surveillance and control of antimicrobial resistance at the human–animal interface, with particular emphasis on programs implemented in the authors' home country, Denmark.

Overview

The epidemiology of antimicrobial-resistant microorganisms at the human–animal interface involves complex and largely unpredictable systems that include transmission routes of resistant bacteria as well as resistance genes and the impact of antimicrobial selective pressures in several reservoirs (animals, humans, and the environment) (Figure A15-1).

A diagram showing the epidemiology of antimicrobial resistance at the human-animal interface

FIGURE A15-1

The epidemiology of antimicrobial resistance at the human–animal interface is invariably complex. It involves a multitude of potential transmission routes and vehicles, antimicrobial selective pressures and other ecological drivers, as well as (more...)

Thus the One Health approach is useful when it comes to addressing zoonotic transmission of pathogens that are resistant to antimicrobials, because we need to engage a wide range of stakeholders including farmers, veterinarians, food safety professionals, medical doctors, as well as environment and wildlife experts in monitoring and control activities.

The feature that particularly differentiates antimicrobial resistance from other food safety–related problems is the role of the chemical driver, the antimicrobials, which selects for the resistant bacteria that subsequently can spread between animals and humans.

Antimicrobials are used widely to prevent or treat disease in food animals. The major part of the usage is for prevention of disease, and their use has become an integral part of modern industrialized food-animal production, to the extent where nearly all feed for growing animals is supplemented with antimicrobials in various doses, ranging from so-called “subtherapeutic concentrations” to full therapeutic doses. It is estimated that the volumes of antimicrobials used in food animals exceeds the use in humans worldwide, and nearly all the classes of antimicrobials that are used for humans are also being used in food animals, including the newest classes of drugs such as third- and fourth-generation cephalosporins, fluoroquinolones, glycopeptides, and streptogramins (Aarestrup et al., 2008).

The massive use of antimicrobial agents in agriculture has supported the intensification of modern food-animal production since the early 1960s by facilitating earlier weaning, higher animal densities, and the use of cheaper feed sources, among others, and has most likely contributed to increased outputs and lower prices of meat. However, the gains have come at a cost, which is being borne, in part, by other stakeholders, in particular public health. Furthermore, the production gains achieved by indiscriminate antimicrobial usage in the 1960s production systems may to a large extent be achievable by other means in modern and more environmentally sustainable food-animal production systems, where higher emphasis is placed on animal welfare, a smaller environmental footprint, and disease prevention through hygiene and intelligent herd management.

The amounts and patterns of antimicrobials used in food animals is the major determinant for the propagation of resistant bacteria in the animal reservoir. Thus, the levels and patterns of resistance observed in food animals to a wide extent reflect the patterns of drug usage; however, other determinants also play a part, such as spread of bacterial clones between animals, in particular vertical spread between the generations (e.g., the spread of resistant Salmonella in the poultry and swine breeding pyramids), and successful adaptation of clones resistant to the animal reservoir (e.g., MRSA CC398) (Aarestrup et al., 2008).

Transmission of resistance from animals to humans can take place through a variety of routes (Figure A15-1), where the food-borne route probably is the most important (most infections with enteric bacterial pathogens, such as Salmonella enterica, Campylobacter coli/jejuni, and Yersinia enterocolitica, probably occur through this route in industrialized countries), whereas, for other resistant pathogens, direct contact between animal and humans may be the major route of transmission (e.g., MRSA CC398). Bacteria as well as antibiotic residues from food-animal production are spread widely in the environment, mainly with manure, where it affects bacteria in the environment as well as in wild fauna. Thus, the environment and wild fauna can become reservoirs of resistance and a source of reintroduction of resistant bacteria into the food-animal and human reservoirs.

The public health consequences of zoonotic antibiotic resistance are invariably difficult to assess for a number of reasons: the epidemiology is highly complex because it involves complex production and distribution systems of animals and food, it involves the spread of bacterial clones as well as resistance genes, and, finally, the impact on public health includes several end points that are difficult to determine, such as infections that would otherwise not have occurred, increased morbidity and mortality, and higher costs of treatment of disease. In the most comprehensive assessment of the problem to date, an expert group gathered by the World Health Organization (WHO), the Food and Agriculture Organization (FAO), and the World Animal Health Organization (OIE) in 2003 concluded

there is clear evidence of adverse human health consequences due to resistant organ isms resulting from non-human usage of antimicrobials. These consequences include infections that would not have otherwise occurred, increased frequency of treatment failures (in some cases death) and increased severity of infections, as documented for instance by fluoroquinolone resistant human Salmonella infections. Evidence shows that the amount and pattern of non-human usage of antimicrobials impact on the occurrence of resistant bacteria in animals and on food commodities and thereby human exposure to these resistant bacteria. The foodborne route is the major transmission pathway for resistant bacteria and resistance genes from food animals to humans, but other routes of transmission exist. There is much less data available on the public health impact of antimicrobial usage in aquaculture, horticulture and companion animals.” (FAO et al., 2003)

Investigating the zoonotic antimicrobial resistance problem in its full complexity requires monitoring of antimicrobial usage and resistance in all relevant reservoirs and stages in the transmission route, and coherent analysis of the data (i.e., “integrated monitoring”). For the purpose of intervention, there are multiple potential points of control that may be used, depending on the specific nature of the problem. Identifying and intervening at the most efficient points of control requires a comprehensive assessment of the risk based on integrated monitoring, as well as good collaboration between all the stakeholders involved.

Already in the early 1960s, findings of resistant Salmonella in food animals and humans, and studies that showed that they could pass their resistance traits on to other enteric bacteria, gave rise to major concern in the United Kingdom. This led to the formation of the “Swann Committee,” which recommended

that only antibiotics which “have little or no application as therapeutic agents in man or animals and will not impair the efficacy of a prescribed therapeutic drug or drugs through the development of resistant strains of organisms” should be usable for growth promotion. (Swann et al., 1969)

This was put into the UK legislation and subsequently the European Union legislation. The United States and the rest of the world, however, did not follow the same path.

In the mid-1990s the detection of vancomycin-resistant Enterococcus f aecium as well as quinolone-resistant Salmonella and Campylobacter in food animals and evidence of their spread to humans elevated the scientific and public concerns to new levels. This prompted a series of international expert consultations and meetings under the auspices of the WHO and/or the OIE, and it also led to implementation of specific interventions to contain antimicrobial resistance in the food-production chain in many countries, most importantly the complete termination of the use of antimicrobial growth promoters in Europe (FAO et al., 2004; WHO, 1997).

Recently a number of antimicrobial-resistant pathogens have emerged in the food-production chain: extended beta-lactamase producing Salmonella and Escherichia coli, transmissible quinolone resistance (qnr) in Salmonella and E. coli and animal-associated methicillin-resistant Staphylococcus aureus (MRSA), which can transmit to, and cause infections in, humans. These emergences can all be associated with the use of antimicrobial agents in food animals, and they have led to renewed attention to the use of certain types of antimicrobials in food animals that are considered critically important for human health (Aarestrup et al., 2008; Xia et al., 2010).

Residues of antimicrobial agents that may occur in animal-derived products appear to be of a lesser concern for public health than the resistant bacteria. A WHO expert committee concluded in 2003 that residues of antimicrobials in foods, under present regulatory regimes, represent a significantly less important human health risk than the risk related to antimicrobial-resistant bacteria in food (FAO et al., 2003).

Use of antibiotic resistance genes as marker genes in genetically modified plants, which may serve as feed for animals or food for humans, has also raised concerns in this context. Recently, the European Food Safety Authority (EFSA) conducted a risk assessment based on the current state of the science and concluded the following: “Notwithstanding these uncertainties, the current state of knowledge indicates that adverse effects on human health and the environment resulting from the transfer of these two antibiotic resistance genes from GM plants to bacteria, associated with use of GM plants, are unlikely” (EFSA, 2009).

Increased overlap between humans and wildlife populations may increase the risk for novel disease emergence in wildlife in a recent study by Wheeler et al. (2012). Antibiotic resistance was used as a molecular marker for the intensity of human–wildlife microbial connectivity in the Galápagos Islands. Antibiotic-resistant bacteria were found in reptile feces from tourism sites, whereas no resistance was detected at protected beaches on more isolated islands, indicating that human contact may be the source of resistant enteric bacteria (E. coli and Salmonella) in Galápagos wildlife (Wheeler et al., 2012).

Recognizing the continued emergence of new bacterial pathogens, in animals, that are resistant to antimicrobials considered critically important for human therapy, there is good reason to further strengthen global efforts to prevent and control the emergence and spread of resistance from animals to humans. The One Health concept and its focus on the interdependencies and links between the three health systems of animals, humans, and the environment, respectively, are extremely well suited for this purpose.

The remaining part of this article describes some examples of national and international interventions to contain antimicrobial resistance in the food-production chain, with main emphasis on interventions employed in the authors' home country, Denmark, which happen to be some of the most advanced and also best documented interventions in this regard.

National and International Attempts to Monitor and Control Transmission of Antimicrobial Resistance Between Animals and Humans

A large number of national and international rules and regulations are involved in the regulation and control of food-borne antimicrobial resistance.

Legal Framework at the International Level

The Codex Alimentarius Commission (CAC), under the WHO and the FAO, has issued recommendations that should be implemented by all countries as a code of practice to minimize and contain antimicrobial resistance (CAC, 2005). This code of practice gives recommendation for the responsibilities of regulatory authorities, the veterinary pharmaceutical industry, veterinarians, and wholesale and retail distributors and producers.

As examples, regulatory authorities should ensure that antimicrobial agents are prescription only (thus, not used for growth promotion), only drugs that are efficacious and with well-established dosages should be approved, surveillance programmes for monitoring drug use and resistance should be established, research should be encouraged, and all unused drug should be collected and destroyed. It is stated that veterinarians should only prescribe drugs for animals under their care and ensure that the drugs used are aimed at clinical disease. In addition, the professional organization should develop clinical practice guidelines on responsible use. In addition to these international recommendations a large number of different national legislation regulates the use of antimicrobial agents and the control of antimicrobial-resistant bacteria.

Below are some examples of control options and their effect on resistance.

Possible Risk Management Options

Currently from a practical and legal point of view, control options are usually divided into pre-harvest (e.g., on farm) and post-harvest (e.g., slaughterhouse and food). However, a more logical way to look at this problem would be to either avoid selection and/or stop the spread of resistant bacteria. Thus, the control of antimicrobial resistance can be controlled either through management of the selective pressure leading to resistance or through interventions aimed at limiting the spread of the selected resistance.

Continuous and updated information is essential to guide risk management and to determine the effect of possible interventions. Thus, continuous monitoring of the occurrence of food-borne pathogens, antimicrobial resistance, and drug use as well as research studies determining the effects of interventions and the associations between different reservoirs, the spread of bacterial clones and genes, and risk factors for the development and spread of resistance are essential for efficient risk management.

Monitoring of Antimicrobial Resistance Information on the occurrence of antimicrobial resistance is needed at the local, national, and international levels to guide policy and detect changes that require intervention strategies. Such monitoring programmes should be continuous and standardized, enabling comparison between countries as well as over time. The main aspects to be considered in establishing a monitoring system include animal or food groups to be sampled, the number of samples to take and the strategy for collection, bacterial species to be included, methods for susceptibility testing, antimicrobials to test, break points to use, quality control, data to be reported, analysis and interpretation of data, and reporting (Bager et al., 1999). The Danish Integrated Antimicrobial Resistance Monitoring Programme (DANMAP) established in 1995 was the first integrated program in Europe (Figure A15-2). Recently a proposal for a common protocol for antimicrobial resistance monitoring was proposed for Europe (EFSA, 2008). It can be hoped that this can form the basis for a future establishment of a common global standard.

Diagram showing the surveillance inputs to DANMAP

FIGURE A15-2

Flow of samples, isolates, and data in the Danish Integrated Antimicrobial Resistance and Antimicrobial Usage Monitoring Programme—DANMAP. SOURCE: DANMAP (2010).

Monitoring of Antimicrobial Drug Use Data on drug usage is essential for the development of national and international policies for containment of antimicrobial resistance. In Denmark, a programme called Vetstat was implemented in August 2000 and has since collected data from veterinarians, pharmacies, and feed mills. The programme monitors the use of all prescription medicine in production animals, including sera and vaccines, as well as the use of coccidiostatics (Stege et al., 2003). Data are collected at the farm level and include information concerning animal species, age of animal, disease, farm identification number, veterinarians' number, drug identification number, amount of medicine, and date for use of medicine. Today Vetstat enables the authorities to assess usage patterns at the level of the individual herd and individual prescriber. Furthermore, many veterinarians use Vetstat daily as a tool in relation to their service for their clients (farmers). Because all data are converted to defined animal daily doses (ADDs) it is possible to compare the use of antibiotics on one farm with a similar average for the whole country.

In 2010 the Danish Veterinary and Food Authority (DVFA) introduced the “Yellow Card Initiative” based on Vetstat (DVFA, 2012). Each year, DVFA will issue threshold limits for antimicrobial consumption in pigs (other animal species may follow later). The limits for pigs in 2010 were as follows:

  1. Weaners (7-30 kg): 28 ADD per 100 weaners per day.
  2. Young pigs, including young females (over 30 kg), excluding sows, gilts, and boars: 8 ADD per 100 pigs per day.
  3. Sows, gilts, and boars: 5.2 ADD per 100 pigs per day.

If the average antimicrobial consumption in a holding within a 9-month period exceeds one or more of the threshold limits, DVFA may issue an order or injunction (the yellow card) compelling the owner of the holding, in collaboration with the veterinary practitioner, to reduce the antimicrobial consumption in the holding below the threshold limits within 9 months.

The total use of antimicrobials in swine has been reduced by 21 percent in Denmark, following the introduction of the Yellow Card Initiative, when comparing national data on usage for the years 2009 and 2011, respectively (DVFA, 2012).

Recently a first attempt to collect comparable veterinary antibiotic usage data for the European countries was carried out (Figure A15-3) (Grave et al., 2010). The rather large differences between the different countries can be explained by differences in types of animal production systems, different veterinary antibiotic policies and practices, or differences in disease occurrence. A recent study reported that a conservative estimate of the comparable figure for the United States was considerably higher, approximately 300 mg/kg (Aarestrup et al., 2010).

A bar graph comparing the sales of veterinary antibacterial agents in 10 European countries

FIGURE A15-3

Comparison of the sales of veterinary antibacterial agents between 10 European countries (mg per kg meat produced). SOURCE: Grave et al. (2010). The comparable figure for the United States is estimated to be approximately 300 mg/kg according to Aarestrup (more...)

Limiting the Selective Pressure

Prescription One of the basic principles in the Codex Alimentarius codes of practice to minimize and contain antimicrobial resistance is that all antimicrobial agents should be on prescription, and the right to prescribe drugs should rest with the veterinarians or other animal health professionals with an appropriate education. Prescribing and dispensing should be separated to avoid conflicts of interest.

Drug Approval All drugs intended for human or animal use undergo an approval process before licensing, which differs somewhat between countries even though some general guidelines are used. The traditional risks that are considered in the approval process include proof of efficacy against the target pathogen, target animal safety, environmental safety, and human health safety with a focus on toxicological effects (residues). Human hazards related to the transfer of antimicrobial resistance are of more recent concern and have so far only had limited focus in the approval process. In 2003 the U.S. Food and Drug Administration (FDA) published a guidance document for a qualitative risk assessment to be performed prior to the approval of an antimicrobial agent for animal use (FDA, 2003). This guideline outlines an evidence-based approach to preventing antimicrobial resistance from emerging in humans as a consequence of using antimicrobial agents in animals. This guidance requires a ranking into high, medium, and low of the following factors: (1) probability that resistant bacteria are present in target animals as a consequence of drug use, (2) probability for humans to ingest the bacteria in question, and (3) probability that human exposure results in an adverse effect. These three factors are then joined together in an overall risk estimate ranked as high, medium, or low. In combining the three factors, the most value is put on the consequence estimate. Thus, in essence, antimicrobial agents considered “critically important” will be ranked as having a high risk no matter what the probability for selection or transfer. Thus, already in the approval process consideration as to whether antimicrobials are of critical importance for human health can be taken into account. As an example, in Australia fluoroquinolone use was never approved for use in food animals. Fluoroquinolone-resistant strains are either at very low levels or nonexistent in food animals. The rates of resistance are also very low in human isolates in comparison to other countries (e.g., community onset bloodstream infection resistance rate in E. coli of 2 percent) (Kennedy et al., 2008).

It is also possible in the approval process to implement certain restrictions. Thus, it could be possible to approve drugs for a limited number of indications, without accepted extralabel or off-label usage or for some modes of administration only (e.g., only parenteral use). This has recently been done by FDA in the United States, which in July 2008 issued an order coming into effect by October 2008 prohibiting the extralabel use of cephalosporin antimicrobial drugs in food-producing animals (FDA, 2008).

Treatment formularies and prescriber guidelines In Denmark a veterinary treatment formulary was published by the National Food Institute in 1997 (Pedersen et al., 1999). This formulary was mainly targeted toward concerns for human health, but it also took into account the prevalence of antimicrobial resistance among bacteria causing infections in animals. In the formulary, antimicrobials for every disease and associated pathogen(s) are listed and scored (1-3) within the following four categories: efficacy, resistance among the pathogen causing infection in animals, national criteria for human importance in Denmark, and WHO criteria for Critically Important Antimicrobials (WHO, 2005).

It is difficult to evaluate the specific effects of the guidelines. However, considering that one of the main recommendations in Denmark has been to limit the use of macrolides and cephalosporins and that the use of these classes of antimicrobials for pigs, which constitutes 80 percent of the usage for animals in Denmark, has increased by 30 and 33 percent, respectively, between 2005 and 2006 (DANMAP, 2006), the effect seems to be minor.

Restrictions on the use of certain antimicrobial classes It is also possible to implement national or international restrictions on certain antimicrobial classes. As mentioned, in Australia fluoroquinolones are not registered for use in food animals. In Denmark fluoroquinolones were approved for use in production animals in 1993, and in the following years an emergence of resistance was observed. In the year 1999 the farmers voluntarily stopped the use of in-feed fluoroquinolones, and in 2002 the veterinarians' use and prescription of fluoroquinolones to food- producing animals were further restricted by the authorities. Thus, fluoroquinolones can only be used in food-producing animals if a current laboratory test of resistance patterns shows that no other antimicrobial will be effective in treatment of the disease in question and this has been reported to the regional veterinary officer. Furthermore, fluoroquinolones can only be administered by injection and by the veterinarian only. This reduced the total usage of fluoroquinolones in animals in Denmark from 183 kg in 2001 to 49 kg in 2006 (Figure A15-4).

A bar graph showing the total consumption in kilograms of fluorquinolones in Danish food animal production

FIGURE A15-4

The total consumption of fluoroquinolones in Danish food-animal production, following voluntary and regulatory efforts to reduce the amounts used in 1999 and 2002, respectively.

Limiting the prescribers' profit on the sale of antimicrobial agents In many countries a considerable part of the veterinarians' income comes from the direct sale of antibiotics to the farmers. This could tempt some veterinarians to overprescribe antibiotics because of the financial benefit. An example from Denmark showed that limiting the possibility of veterinarians to profit from the sale of drugs led to a reduction in total usage. In 1995 the Danish government issued a new legislation reducing and fixing the veterinarians' profit from the direct sale of antibiotics to a maximum of 5 percent. Furthermore, a veterinarian can only sell antibiotics to a farmer during a visit and for a maximum of 5 days of use. The rest has to be bought at a pharmacy. This resulted in a reduction of 40 percent in total use of therapeutic agents and a reduction in tetracycline use from almost 37 tonnes in 1994 to 9 tonnes in 1995 (Grave and Wegener, 2003).

Price and taxation In human medicine several studies have shown an association between expenses and the prescription of a specific drug. It is a reasonable assumption that the cost of the drug is a considerable factor for the farmer's decision on when and how to use antimicrobials over other disease control and prevention options. In Denmark, a tax was imposed on antimicrobial growth promoters in 1998. The purpose of the tax was to remove the postulated financial benefit from using the antimicrobial growth promoters. From 1998, and until the ban in 2000, a sharp reduction on overall use of antimicrobial growth promoters occurred, but this could also be explained by other factors such as public and media attention, implementation of industry codes of practice, etc. More scientific studies addressing the effects of taxation as a risk management tool are needed.

Voluntary withdrawals or banning of drugs In the United Kingdom the use of tetracyclines and penicillin as growth promoters was banned following the recommendation the Swann report.

In 1995 the Danish Ministry of Agriculture, Fisheries and Food decided to ban the use of the growth promoter avoparcin because of its cross-resistance to vancomycin, a critically important antimicrobial for human use. In 1997, the European Union (EU) banned the use of avoparcin. In 1998 Denmark banned the use of virginiamycin because of cross-resistance to the critical important Quinupristin-Dalfopristin used in humans. In 1998, the Danish animal production industry voluntarily stopped the use of growth promoters; only swine up to 35 kg bodyweight were still treated with growth promoters until January 2000. In 1999 the EU banned tylosin, spiramycin, virginiamycin, and bacitracin, and the remaining growth pro moters were banned in the EU from January 2006. The gradual banning of growth promoters in Denmark resulted in a 50 percent reduction of the usage of antimicrobial agents in animal production from 1997 to 1998, and consequential reductions in the levels of antimicrobial resistance in a range of different bacterial species in food animals (Figures A15-5 and A15-6) (Aarestrup et al., 2008).

A graph plotting resistance to erythromycin in swine and the consumption of macrolides

FIGURE A15-5

Resistance (%) to erythromycin among Enterococcus faecium and Enterococcus faecalis from swine (left Y axis) and the consumption of macrolides in swine, Denmark (right Y axis). SOURCE: DANMAP (2010).

A graph showing resistance to vancomycin in broilers and the consumption of avoparcin

FIGURE A15-6

Resistance (%) to vancomycin in Enterococcus faecium from broilers and the consumption of avoparcin, Denmark. SOURCE: DANMAP (2010).

In the first quarter of 2005 there was a voluntary withdrawal in Québec chicken hatcheries of the extralabel use of ceftiofur. After the withdrawal, a significant decrease in ceftiofur resistance was seen in Salmonella Heidelberg isolates from retail chicken and humans, as well as in E. coli from retail chickens (Figure A15-7) (Dutil et al., 2010).

A line graph showing the prevalence of ceftiofur resistance in retail chicken E. coli and human clinical Salmonella

FIGURE A15-7

Prevalence of ceftiofur resistance (moving average of the current quarter and the previous two quarters) among retail chicken Escherichia coli, and retail chicken and human clinical Salmonella enterica serovar Heidelberg isolates during 2003-2008 in Québec. (more...)

The examples above show that reduction in the use of antimicrobial agents can have a positive effect on the occurrence of antimicrobial resistance. The disadvantage of relying on voluntary withdrawals is that there are no controls that prevent the same groups from later reintroducing these antibiotics and the consequential rapid rise in resistance rates that will result. In fact the chicken hatcheries in Québec have already begun using ceftiofur again.

Preventive veterinary medicinal strategies Disease prevention is an integrated part of food-animal production, and Specific Pathogen Free swine and poultry production systems use this option actively. Preventing disease is considered an essential factor in reducing antimicrobial usage. Strangely only few published scientific studies seem to have addressed this specific point. The most likely explanation for the lack of scientific confirmation thereof is the lack of combined data on management systems, drug use, disease incidence, and antimicrobial resistance.

In a study from Norway the effect of introducing vaccines for prevention of disease in farmed salmon was investigated. The introduction of vaccines led to a substantial reduction in the use of antimicrobials in Norwegian aquaculture (Figure A15-8) (Markestad and Grave, 1997).

A bar graph showing sales of antimicrobials for therapeutic use in farmed fish from Norway

FIGURE A15-8

Sales of antimicrobials for therapeutic use in farmed fish in Norway versus produced biomass. SOURCE: NORM/NORM-VET (2010).

It is important to note that whenever antibiotics have been removed as routine food additives for growth promotion and disease prevention purposes there has been no or little evidence that this has resulted in any decrease in animal health or food production.

Controlling Spread of Resistant Bacteria Improved hygiene and infection control is a well-established and essential part of controlling infectious diseases. Improving the general hygiene in all stages of production and thereby reducing the microbial load on food products will also reduce the antimicrobial resistance load. However, a number of additional options aimed directly at reducing antimicrobial resistance are available for authorities and other stakeholders.

Setting thresholds for the acceptable level of pathogenic bacteria in foodstuffs is a well-established risk management praxis. Thresholds exist for a wide range of bacterial species or subtypes in foodstuffs (e.g., Listeria monocytogenes and E. coli O157:H7). Thus, establishing thresholds for bacteria resistant to certain antimicrobials is a valid, however rarely used, option to be considered. In Denmark, a specific control programme aimed at S. Typhimurium DT104 was implemented in 1998 (Wegener, 2006). As a part of this programme a zero tolerance for DT104 in food was established. The programme has led to a reduction of DT104 in domestically produced and imported foodstuffs.

While several food safety standards for traded food products exist, there seems to be a bigger problem in relation to the trade of live animals. Requirements in relation to epizootic diseases do exist, but none seem to be in place in relation to zoonotic bacteria or in particular antimicrobial resistance. Thus, today breeding animals with resistant Salmonella and other pathogens can be traded freely between countries, constituting an efficient route of global dissemination of resistant bacteria.

Conclusions

Integrated surveillance systems are essential to monitor the emergence and spread of antimicrobial resistance along the food production chain. Such systems require

  • systematic sampling, harmonized laboratory methods, and good data management;
  • detailed denominator data about the origin of the samples;
  • subtyping of bacterial isolates, and molecular characterization of resistance genes;
  • detailed antimicrobial usage data; and,
  • flawless collaboration and coordination, including sharing and comparing data.

Based on existing surveillance systems it is fair to conclude the following:

  • There is a close relationship between the patterns of antimicrobial usage and the observed patterns of antimicrobial resistance in food animals; however, other factors such as co-selection and clonal spread also play a part.
  • There is a close relationship between levels and patterns of antimicrobial resistance in the food supply and antimicrobial resistance in human foodborne infections, bearing in mind that some food is imported and other foods are consumed while travelling abroad, and that all sources need to be accounted for.

There is a great need to reduce the overall use of antimicrobials in agri- and aquaculture worldwide, and the experiences from different countries suggest that major reductions can be achieved without significant negative effects on animal health or productivity, and for the long-term benefit of public, environmental, and animal health.

A number of effective upstream interventions to reduce resistance have been documented, including banning nontherapeutic uses in food animals, enforcing prescription-only policies, removing financial incentives for prescribing therapeutic drugs, restricting the use of drugs considered critically important for human health, monitoring usage at the farm level and providing advice to high-end users, and establishing thresholds for resistant pathogens in food.

Reducing antimicrobial usage requires collaboration between experts, regulatory authorities, and producers, and integrated monitoring of the effects of interventions is essential. This may be facilitated by establishing a coordinating body, for example, an antibiotic council, including all relevant stakeholders.

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Provost, Chief Academic Officer, Technical University of Denmark, Anker Engelunds Vej 1, 2800 Lyngby, Denmark.

Copyright © 2012, National Academy of Sciences.
Bookshelf ID: NBK114485

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