One Health is the collaborative effort of multiple health science professions to attain optimal health for people, domestic animals, wildlife, plants, and our environment. The drivers of antimicrobial resistance include antimicrobial use and abuse in human, animal, and environmental sectors and the spread of resistant bacteria and resistance determinants within and between these sectors and around the globe. Most of the classes of antimicrobials used to treat bacterial infections in humans are also used in animals. Given the important and interdependent human, animal, and environmental dimensions of antimicrobial resistance, it is logical to take a One Health approach when addressing this problem. This includes taking steps to preserve the continued effectiveness of existing antimicrobials by eliminating their inappropriate use and by limiting the spread of infection. Major concerns in the animal health and agriculture sectors are mass medication of animals with antimicrobials that are critically important for humans, such as third-generation cephalosporins and fluoroquinolones, and the long-term, in-feed use of medically important antimicrobials, such as colistin, tetracyclines, and macrolides, for growth promotion. In the human sector it is essential to prevent infections, reduce over-prescribing of antimicrobials, improve sanitation, and improve hygiene and infection control. Pollution from inadequate treatment of industrial, residential, and farm waste is expanding the resistome in the environment. Numerous countries and several international agencies have included a One Health approach within their action plans to address antimicrobial resistance. Necessary actions include improvements in antimicrobial use regulation and policy, surveillance, stewardship, infection control, sanitation, animal husbandry, and alternatives to antimicrobials. WHO recently has launched new guidelines on the use of medically important antimicrobials in food-producing animals, recommending that farmers and the food industry stop using antimicrobials routinely to promote growth and prevent disease in healthy animals. These guidelines aim to help preserve the effectiveness of antimicrobials that are important for human medicine by reducing their use in animals.

Background: There is growing concern worldwide about the role of polluted soil and water environments in the development and dissemination of antibiotic resistance.Objective: Our aim in this study was to identify management options for reducing the spread of antibiotics and antibiotic-resistance determinants via environmental pathways, with the ultimate goal of extending the useful life span of antibiotics. We also examined incentives and disincentives for action.Methods: We focused on management options with respect to limiting agricultural sources; treatment of domestic, hospital, and industrial wastewater; and aquaculture.Discussion: We identified several options, such as nutrient management, runoff control, and infrastructure upgrades. Where appropriate, a cross-section of examples from various regions of the world is provided. The importance of monitoring and validating effectiveness of management strategies is also highlighted. Finally, we describe a case study in Sweden that illustrates the critical role of communication to engage stakeholders and promote action.Conclusions: Environmental releases of antibiotics and antibiotic-resistant bacteria can in many cases be reduced at little or no cost. Some management options are synergistic with existing policies and goals. The anticipated benefit is an extended useful life span for current and future antibiotics. Although risk reductions are often difficult to quantify, the severity of accelerating worldwide morbidity and mortality rates associated with antibiotic resistance strongly indicate the need for action.

Antibiotic resistance and associated genes are ubiquitous and ancient, with most genes that encode resistance in human pathogens having originated in bacteria from the natural environment (eg, β-lactamases and fluoroquinolones resistance genes, such as qnr). The rapid evolution and spread of "new" antibiotic resistance genes has been enhanced by modern human activity and its influence on the environmental resistome. This highlights the importance of including the role of the environmental vectors, such as bacterial genetic diversity within soil and water, in resistance risk management. We need to take more steps to decrease the spread of resistance genes in environmental bacteria into human pathogens, to decrease the spread of resistant bacteria to people and animals via foodstuffs, wastes and water, and to minimize the levels of antibiotics and antibiotic-resistant bacteria introduced into the environment. Reducing this risk must include improved management of waste containing antibiotic residues and antibiotic-resistant microorganisms.

Background: Only recently has the environment been clearly implicated in the risk of antibiotic resistance to clinical outcome, but to date there have been few documented approaches to formally assess these risks.Objective: We examined possible approaches and sought to identify research needs to enable human health risk assessments (HHRA) that focus on the role of the environment in the failure of antibiotic treatment caused by antibiotic-resistant pathogens.Methods: The authors participated in a workshop held 4–8 March 2012 in Québec, Canada, to define the scope and objectives of an environmental assessment of antibiotic-resistance risks to human health. We focused on key elements of environmental-resistance-development “hot spots,” exposure assessment (unrelated to food), and dose response to characterize risks that may improve antibiotic-resistance management options.Discussion: Various novel aspects to traditional risk assessments were identified to enable an assessment of environmental antibiotic resistance. These include a) accounting for an added selective pressure on the environmental resistome that, over time, allows for development of antibiotic-resistant bacteria (ARB); b) identifying and describing rates of horizontal gene transfer (HGT) in the relevant environmental “hot spot” compartments; and c) modifying traditional dose–response approaches to address doses of ARB for various health outcomes and pathways.Conclusions: We propose that environmental aspects of antibiotic-resistance development be included in the processes of any HHRA addressing ARB. Because of limited available data, a multicriteria decision analysis approach would be a useful way to undertake an HHRA of environmental antibiotic resistance that informs risk managers.Citation: Ashbolt NJ, Amézquita A, Backhaus T, Borriello P, Brandt KK, Collignon P, Coors A, Finley R, Gaze WH, Heberer T, Lawrence JR, Larsson DG, McEwen SA, Ryan JJ, Schönfeld J, Silley P, Snape JR, Van den Eede C, Topp E. 2013. Human health risk assessment (HHRA) for environmental development and transfer of antibiotic resistance. Environ Health Perspect 121:993–1001; http://dx.doi.org/10.1289/ehp.1206316

Intensive use of antimicrobial agents in aquaculture provides a selective pressure creating reservoirs of drug-resistant bacteria and transferable resistance genes in fish pathogens and other bacteria in the aquatic environment. From these reservoirs, resistance genes may disseminate by horizontal gene transfer and reach human pathogens, or drug-resistant pathogens from the aquatic environment may reach humans directly. Horizontal gene transfer may occur in the aquaculture environment, in the food chain, or in the human intestinal tract. Among the antimicrobial agents commonly used in aquaculture, several are classified by the World Health Organisation as critically important for use in humans. Occurrence of resistance to these antimicrobial agents in human pathogens severely limits the therapeutic options in human infections. Considering the rapid growth and importance of aquaculture industry in many regions of the world and the widespread, intensive, and often unregulated use of antimicrobial agents in this area of animal production, efforts are needed to prevent development and spread of antimicrobial resistance in aquaculture to reduce the risk to human health.

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Bacteria have evolved multiple mechanisms for the efficient evolution and spread of antimicrobial resistance. Modern food production facilitates the emergence and spread of resistance through the intensive use of antimicrobial agents and international trade of both animals and food products. The main route of transmission between food animals and humans is via food products, although other modes of transmission, such as direct contact and through the environment, also occur. Resistance can spread as resistant pathogens or via transferable genes in different commensal bacteria, making quantification of the transmission difficult. The exposure of humans to antimicrobial resistance from food animals can be controlled by either limiting the selective pressure from antimicrobial usage or by limiting the spread of the bacteria/genes. A number of control options are reviewed, including drug licensing, removing financial incentives, banning or restricting the use of certain drugs, altering prescribers behavior, improving animal health, improving hygiene and implementing microbial criteria for certain types of resistant pathogens for use in the control of trade of both food animals and food.

The use of antimicrobials in food animals creates an important source of antimicrobial-resistant bacteria that can spread to humans through the food supply. Improved management of the use of antimicrobials in food animals, particularly reducing the usage of those that are "critically important" for human medicine, is an important step toward preserving the benefits of antimicrobials for people. The World Health Organization has developed and applied criteria to rank antimicrobials according to their relative importance in human medicine. Clinicians, regulatory agencies, policy makers, and other stakeholders can use this ranking when developing risk management strategies for the use of antimicrobials in food production animals. The ranking allows stakeholders to focus risk management efforts on drugs used in food animals that are the most important to human medicine and, thus, need to be addressed most urgently, such as fluoroquinolones, macrolides, and third- and fourth-generation cephalosporins.