Introduction

Antimicrobial agents are used widely in agriculture to treat and prevent disease, promote growth, and enhance feed efficiency in food animals. Because their use may contribute significantly to the development of antimicrobial resistance, such uses are not without consequences for human, animal, and environmental health. Outright treatment failure due to antimicrobial resistance is an obvious concern; moreover, exposure to antimicrobials can fundamentally alter microbial ecosystems in humans and animals as well as in the environment. In addition, antimicrobial resistance can potentially increase the number of infections each year and can be associated with the emergence of more virulent bacterial pathogens, leading to more severe infections. Increasing recognition and understanding of these and other risks have prompted some experts to urge that certain of these agricultural practices be curtailed, both to preserve the effectiveness of antimicrobial agents needed for treatment of infections in humans and animals and to decrease the environmental pool of resistant bacteria. This opinion raises critical public policy questions concerning the appropriate agricultural use of antimicrobial agents. To address the scientific issues underlying these questions, the Alliance for the Prudent Use of Antibiotics (APUA) initiated a 2-year project, called “Facts about Antimicrobials in Animals and the Impact on Resistance (FAAIR).” APUA convened a Scientific Advisory Panel (“Panel”), whose charge was to gather evidence and draw conclusions about human health impacts of antimicrobial use in agriculture. The Panel was composed of experts from a variety of fields, including human and veterinary medicine, plant pathology, public health, microbiology, and biostatistics and risk analysis. Panel members undertook a comprehensive review of the existing body of scientific and medical evidence, to which they added novel analyses, conclusions, and recommendations intended to influence public policy. In 1969, the Swann Committee in the United Kingdom published a watershed report recommending more restricted use of antimicrobials in agriculture. Despite this and similar recommendations in reports from national and international health and nongovernmental organizations since then, the debate over the human health risks associated with antimicrobial use in agriculture continues. Regulatory officials in the European Union, Australia, Japan, New Zealand, and other nations have invoked the “precautionary principle” in restricting some agricultural uses of antimicrobials. US officials are also considering imposing additional restrictions to prevent or postpone the development of resistance in pathogens transmissible from food animals to humans. There has been widespread debate about the risks and benefits of such a policy change. Critical questions relevant to this debate in the United States include the following: (1) How much of total antimicrobial use is directed toward food animal production as opposed to human medicine? and (2) Of the antimicrobials administered to food animals, what proportion is used for treatment and prevention of infections as opposed to nontherapeutic uses? Precise information for these uses is not publicly available. APUA and the FAAIR Panel intend this report to provide an objective, scientific review and analysis of available data on antimicrobial resistance as it pertains to antimicrobial use in agriculture. While past reports have focused narrowly on clinical studies, the FAAIR Project enlarged the scope of inquiry to include an ecological dimension of antimicrobial resistance. Antimicrobial use in medicine and agriculture affects the general ecology of bacterial communities, including interactions between microorganisms and their environments and mechanisms by which antimicrobial resistance traits spread and persist. This perspective facilitates an understanding of the broad consequences of antimicrobial use. This ecological framework provides an essential perspective for formulating antimicrobial use policies precisely because it encompasses the root causes of these problems rather than merely their symptoms. Resistant pathogens in the environment may infect people through direct contact or by indirect means, as through the food supply. This report also considers the potential importance of resistance acquired by commensal microorganisms in food animals or in humans, as these ordinarily nonpathogenic bacteria may provide a reservoir of resistance genes that can be transferred to human pathogens. APUA initiated the FAAIR project in accord with its mission, which is to improve control of infectious disease worldwide through more appropriate use of antibiotics and reduction of antibiotic resistance. To this end, the Panel and APUA offer the following evidence, analyses, and recommendations for use in facilitating discussion and improving public policy and practices related to agricultural use of antimicrobials.