What % Of Antibiotics Produced Are Used On Animals In The Us
Public Health Rep. 2012 Jan-Feb; 127(i): 4–22.
A Review of Antibiotic Use in Food Animals: Perspective, Policy, and Potential
Timothy F. Landers
aThe Ohio State University, College of Nursing, Columbus, OH
Bevin Cohen
bCenter for Interdisciplinary Research to Reduce Antibiotic Resistance, Columbia University School of Nursing, New York, NY
Thomas E. Wittum
cThe Ohio State University, Department of Veterinarian Preventive Medicine, Columbus, OH
Elaine 50. Larson
bCenter for Interdisciplinary Enquiry to Reduce Antibiotic Resistance, Columbia Academy School of Nursing, New York, NY
SYNOPSIS
Antibiotic use plays a major role in the emerging public health crisis of antibody resistance. Although the bulk of antibiotic utilize occurs in agricultural settings, relatively little attending has been paid to how antibiotic utilize in farm animals contributes to the overall problem of antibiotic resistance. The aim of this review is to summarize literature on the function of antibiotics in the development of resistance and its hazard to human wellness. We searched multiple databases to identify major lines of statement supporting the role of agronomical antibiotic utilize in the development of resistance and to summarize existing regulatory and policy documents. Several lines of reasoning support the conclusion that agricultural antibiotics are associated with resistance, yet nearly public policy is based on expert opinion and consensus. Finally, nosotros propose strategies to accost current gaps in knowledge.
Antibiotic resistance is a looming public health crisis. While once believed to exist the province of hospitals and other health-intendance facilities, a host of community factors are now known to promote antibody resistance, and community-associated resistant strains have now been implicated as the cause of many hospital-caused infections.ane , two An inherent outcome of exposure to antibiotic compounds, antibody resistance arises equally a result of natural pick.3 Due to normal genetic variation in bacterial populations, individual organisms may carry mutations that render antibiotics ineffective, conveying a survival advantage to the mutated strain. In the presence of antibiotics, advantageous mutations tin likewise be transferred via plasmid exchange within the bacterial colony, resulting in proliferation of the resistance trait.4 The emergence of drug resistance has been observed post-obit the introduction of each new class of antibiotics, and the threat is compounded by a slow drug development pipeline and express investment in the discovery and development of new antibiotic agents.5 – 7
International, national, and local antibiotic stewardship campaigns have been developed to encourage prudent utilise of and limit unnecessary exposure to antibiotics, with the ultimate goal of preserving their effectiveness for serious and life-threatening infections.8 , 9 In practice, however, clinicians must balance the utilitarian goal of preserving the effectiveness of antibiotics with upstanding obligations to patients who present with conditions that are unlikely to be harmed and may benefit from antibiotic use. There is also considerable debate in veterinarian medicine regarding use of antibiotics in animals raised for human consumption (food animals). The potential threat to human health resulting from inappropriate antibiotic utilize in food animals is pregnant, as pathogenic-resistant organisms propagated in these livestock are poised to enter the food supply and could be widely disseminated in nutrient products.x – 15 Commensal bacteria found in livestock are oft nowadays in fresh meat products and may serve as reservoirs for resistant genes that could potentially be transferred to pathogenic organisms in humans.sixteen , 17
While antibody use in food animals may represent a take a chance to homo health, the degree and relative touch have not been well characterized. Given divergent stakeholder interests and inadequate enquiry to date, public policy discussions of this consequence are oftentimes contentious and highly polarized. The aim of this review is to examine the scope and nature of antibiotic apply in nutrient animals and summarize its potential touch on on homo health. Nosotros also review key national and international policies on apply of antibiotics in food animals. Finally, we propose future directions for research and monitoring of the agricultural use of antibiotics.
METHODS
Nosotros searched three online databases of medical and scientific literature citations—the National Library of Medicine's MEDLINE®, the U.South. Department of Agriculture's National Agricultural Library Catalog (known as AGRICOLA), and Thomson Reuter's Web of Science—for English language-language documents from 1994–2009 containing the keywords "antibiotic," "antibiotic resistance," "antimicrobial," "antimicrobial resistance," "agriculture," "livestock," "food creature," "subcontract animal," "pig," "swine," "cattle," "cow," "poultry," and "craven." Two authors reviewed the references and selected exemplary original research articles examining the clan between antibiotic employ in nutrient animals and antibiotic-resistant leaner in humans. We as well performed searches of the ROAR Commensal Literature Database (office of the Reservoirs of Antibiotic Resistance [ROAR] project, coordinated by the Brotherhood for Prudent Utilize of Antibiotics and funded by a grant from the National Institute of Allergy and Infectious Diseases) and the World Health Arrangement (WHO) website to identify research articles and policy documents pertaining to antibiotic use in food animals. An online search engine was used to locate policy statements published by governmental agencies.
RESULTS
In our review, we establish that the utilize of antibiotics in nutrient animals is widespread, yet poorly characterized. Furthermore, in existing studies, neither the risks to homo health nor the benefits to animal production accept been well studied. Nosotros too constitute a lack of consistency in national and international policies.
In the post-obit sections, we review the current literature on the nature and telescopic of antibiotic use in food animals, and on the epidemiologic links between use of antibiotics in food animals and resistance in humans. Nosotros and so provide an overview of the complex risk analysis framework required to understand this problem. Finally, nosotros review key national and international policy and regulatory recommendations.
Literature on the nature and scope of antibiotic employ in nutrient animals
The high population density of modern intensively managed livestock operations results in sharing of both commensal flora and pathogens, which can exist conducive to rapid dissemination of infectious agents. Every bit a result, livestock in these environments normally require aggressive infection management strategies, which oftentimes include the use of antibiotic therapy.
Antibiotics are used in nutrient animals to treat clinical disease, to forbid and control common illness events, and to heighten creature growth.eighteen The unlike applications of antibiotics in food animals accept been described every bit therapeutic use, rubber use, and subtherapeutic apply. Antibiotics can be used to treat a single animal with clinical disease or a large group of animals. However, these various uses are frequently indistinct; definitions of each type of use vary, and the approaches are often practical concurrently in livestock populations.nineteen For example, 16% of all lactating dairy cows in the U.S. receive antibiotic therapy for clinical mastitis each year, but nearly all dairy cows receive intramammary infusions of prophylactic doses of antibiotics following each lactation to preclude and control hereafter mastitis—primarily with penicillins, cephalosporins, or other beta-lactam drugs.20 Similarly, fifteen% of beef calves that enter feedlots receive antibiotics for the treatment of clinical respiratory affliction, but therapeutic antibody doses are also administered to 10% of apparently healthy calves to mitigate predictable outbreaks of respiratory disease.21 Xl-ii percent of beefiness calves in feedlots are fed tylosin—a veterinary macrolide drug—to forestall liver abscesses that negatively impact growth, and approximately 88% of growing swine in the U.South. receive antibiotics in their feed for disease prevention and growth promotion purposes, commonly tetracyclines or tylosin.22 Nigh antibiotic employ in livestock requires a veterinary prescription, although individual treatment decisions are ofttimes made and administered past lay subcontract workers in accord with guidelines provided past a veterinarian.23 , 24
Despite the widespread adoption of antibiotic employ in food animals, reliable data about the quantity and patterns of use (east.g., dose and frequency) are not bachelor.25 Quantifying antibody use in food animals is challenging due to variations in study objectives—investigators may measure out but therapeutic uses, only nontherapeutic uses, or a combination thereof, depending on their outcome of involvement—and lack of clarity surrounding the definitions of therapeutic vs. nontherapeutic uses.26 Although limited, the available data suggest that nutrient animal production is responsible for a significant proportion of antibiotic utilize. In 1989, the Institute of Medicine estimated that approximately half of the 31.nine million pounds of antimicrobials consumed in the U.S. were for nontherapeutic use in animals.27 More recent estimates by the Union of Concerned Scientists, an advocacy grouping that supports reduced agricultural antimicrobial use, suggest that 24.vi one thousand thousand pounds of antimicrobials are used for nontherapeutic purposes in chickens, cattle, and swine, compared with merely 3.0 million pounds used for man medicine. Calculations past the pharmaceutical manufacture-sponsored Fauna Health Institute are more than conservative, suggesting that of 17.viii one thousand thousand pounds of antimicrobials used for animals, merely 3.1 1000000 pounds are used nontherapeutically.26 Twelve classes of antimicrobials—arsenicals, polypeptides, glycolipids, tetracyclines, elfamycins, macrolides, lincosamides, polyethers, beta-lactams, quinoxalines, streptogramins, and sulfonamides—may exist used at different times in the life bike of poultry, cattle, and swine.25 While some of the antimicrobials used in animals are not currently used to treat human disease, many, such every bit tetracyclines, penicillins, and sulfonamides, are also used in the treatment of infections in humans.26 The WHO has developed criteria for the nomenclature of antibiotics as "critically important," "highly important," and "important" based on their importance in the treatment of human disease.28 , 29
However, other classes of antimicrobials used in agriculture have not led to concerns about dissemination of resistance in humans. For example, some of the most frequently used antibiotics in ruminants are ionophores, a distinctive class of antibiotics that alter intestinal flora to achieve increased energy and amino acrid availability and improved nutrient utilization. Most beef calves in feedlots and some dairy heifers receive this drug routinely in their feed. Because of their specific mode of action, ionophores take never been used in humans or therapeutically in animals. While some bacteria are intrinsically resistant to these drugs, at that place is currently no evidence to suggest that ionophore resistance is transferable or that co-selection for resistance to other classes of antimicrobials occurs.xxx
Literature suggesting epidemiologic prove of an association between antibiotic use in food animals and antibiotic resistance in humans
Evidence that antibody use in food animals can consequence in antibiotic-resistant infections in humans has existed for several decades. Associations between antibiotic use in food animals and the prevalence of antibody-resistant leaner isolated from those animals take been detected in observational studies too as in randomized trials. Antibiotic-resistant bacteria of creature origin have been observed in the environment surrounding livestock farming operations, on meat products available for buy in retail food stores, and as the cause of clinical infections and subclinical colonization in humans. Effigy 1 outlines a sampling of prevalence studies, outbreak investigations, ecological studies, case-control studies, and randomized trials whose results suggest a potential human relationship betwixt antibiotic utilise in food animals and antibiotic resistance in humans.
Literature on the risks and benefits of antibiotic utilise in nutrient animals
To empathise how antibiotic utilise in agriculture might impact the emergence of antibody resistance, it is essential to consider the complex interaction of elements in the physical environment (e.k., air, soil, and water) with social exchanges (due east.grand., between animals within a herd, farmers and animals, and domestic poultry and migratory birds), in processing steps (east.g., farming activities, transportation, and storage), and in man use patterns (e.g., food preparation, meat consumption, and susceptibility to infection) (Figure 2). Antibiotic employ in animals can have straight and indirect effects on human being health: directly effects are those that can be causally linked to contact with antibiotic-resistant bacteria from food animals, and indirect effects are those that result from contact with resistant organisms that accept been spread to various components of the ecosystem (east.g., water and soil) every bit a issue of antibiotic use in food animals (Figure 3).
Figure three.
Examples of straight and indirect furnishings of antibiotic utilize in food animals on human health
Given the multitude of factors that contribute to the pathways by which antibiotic use in food animals could pose risks to homo health, information technology is not surprising that a wide variety of methods has been used by researchers in various disciplines to approach the problem. In general, risk cess models in veterinary medicine emphasize animal health and handling of diseases in animals, nutrient scientists' studies focus on the safe of human being food supplies and the presence of antibiotic-resistant bacteria on food products, clinicians and epidemiologists investigate human outbreaks caused by resistant infections for which animals are identified every bit main sources, and molecular biologists examine relationships betwixt resistant strains and the prevalence of specific resistance genes in human and fauna bacteria. It is unlikely that whatever single report will exist able to fully and accurately quantify the relationship between antibody use in food animals and infections in humans. At best, just crude estimates of the etiologic fraction or "impact fraction" can exist made for specific links in the ecologic chain.31
Several mathematical models take been proposed to quantify the overall risk associated with antibiotic use in animals, typically past estimating the prevalence of infection with a specific organism and its associated morbidity, and then multiplying by the proportion of these infections believed to be attributable to antibody use in food animals. While models of this nature have been rightfully criticized for failing to include indirect risk and, consequently, underestimating total potential risk, felicitous gamble assessment strategies must also consider the potential benefits of antibiotic employ in food animals. Even though agricultural antibody employ carries a demonstrated risk, there are likely benefits to the agricultural use of antibiotics as well. For example, reducing animal microbial load and shedding could pb to safer, more than affordable food. However, many of the claims of benefit take not been fully demonstrated in big-scale trials, and other trials have shown that the overall impact of the short-term do good is poorly described.
The U.Southward. Food and Drug Assistants (FDA) requires manufacturers of new antibiotics to perform hazard assessments to demonstrate that new drugs are safe and effective for use in animals and that "there is reasonable certainty of no damage to human being health from the proposed utilise of the drug in food-producing animals."32 To evaluate potential homo health consequences, the FDA employs a qualitative framework to allocate as "depression," "medium," or "high" the probabilities that bacteria in the creature population will acquire resistance, that humans will ingest the resistant leaner in nutrient products, and that ingesting the bacteria volition issue in agin health outcomes (Effigy 4). Drug approval decisions are based on these risk estimations, forth with information about proposed marketing condition (east.g., prescription, over-the-counter, or veterinary feed additives), extent of limitations on extra-characterization use, and intended use patterns (e.g., duration of apply and assistants to individual animals vs. select groups of animals vs. flocks or herds of animals). "High-take chances" drugs may be approved if the FDA determines that homo wellness risk tin be mitigated. "Medium-risk" drugs could be approved if appropriate label restrictions are required.
In add-on to the directly risk assessment model, the FDA has adult guidance to determine the risk of antibiotic residues remaining on food products.32 This guidance recommends determining the impact of antibody residues on normal human intestinal flora and the presence of resistance in these strains, and it provides guidelines for the adding of Acceptable Daily Intake (ADI) for antibiotic residues that pose an observable run a risk to human health.
Guidelines and recommendations on the apply of antibiotics in food animals
Given the importance of antibiotic resistance as a public health trouble, many governments and professional person societies have reviewed existing scientific bear witness and developed recommendations to limit all types of antibiotic apply, including use in food animals. Depending on the nature and jurisdiction of each group, the findings may provide all-time practise guidelines for antibiotic employ, prioritized agendas for research on the emergence of antibiotic resistance, recommendations for legislative action to regulate drug blessing and surveillance processes, or enforceable laws on the manufacture, distribution, and prescription of antibiotics. Figure 5 summarizes recommendations straight related to use of antibiotics in food animal production for a sample of national and international guidance and policy documents.
Give-and-take
Despite increasingly widespread recognition that antibody use in food animals is an important contributor to human infections with antibiotic-resistant leaner (Figure 1), there remains a significant need for scientific testify of the antibiotic utilize practices that create the greatest human being wellness adventure. Our goal with this article was not to propose specific solutions to the trouble—in role because nosotros believe there are no easy, specific answers—simply rather to reiterate and summarize the importance of this issue and to suggest some general policy directions that are indicated. As the importance of the trouble and complexity of the issues are increasingly appreciated past the public, policy dialogue, focused enquiry, and informed regulatory activeness can be undertaken. To facilitate farther research and timely action in response to emerging knowledge on this upshot, nosotros propose the post-obit measures, which are in concert with WHO's global strategy for the containment of antimicrobial resistance, the U.Due south. Interagency Task Strength on Antibiotic Resistance's public health action plan to combat antimicrobial resistance, and the Infectious Diseases Society of America'south telephone call to action.33 – 35
Develop a scientific calendar to recommend advisable study designs and specific aims related to antimicrobial use in food animals
A coordinated program is needed to place missing scientific information and to specify research designs and methods to address these needs. Although rigorous studies have been conducted in some disciplines, there has been a lack of serious and harmonized interdisciplinary effort to expand on the corpus of knowledge, which should be used to inform public policy. To result in a useful and complete list of research priorities, the agenda must include contributions by experts in bones sciences (e.m., genetics and microbiology), clinical sciences (e.thousand., veterinary medicine and human medicine), public health (east.g., epidemiology and nursing), social sciences (eastward.one thousand., anthropology and sociology), economics (e.k., health and agriculture), and public policy (e.m., legislative and regulatory). Research goals put along in the agenda should be reflective of methodological weaknesses identified in the existing literature. For example, definitions of antibiotic uses in food animals (east.g., therapeutic and subtherapeutic) should exist standardized and designed to reflect specific goals (e.g., improving production or preventing economic loss from unrestrained affliction); the terms should be recognized across disciplines and used to classify the potential effects of dissimilar types of antibiotic use on homo health. Another potential focus could be whether to approach research on the development of resistance narrowly (i.e., the causes and furnishings of specific drug-organism combinations) or broadly (i.eastward., the causes and effects of all antibiotics used in animals on microbial flora) to develop public health recommendations.
Fund agricultural research that reflects the priorities identified by the enquiry agenda
Inadequate funding for agricultural research has likely contributed to the lack of sufficient scientific evidence necessary for informing public health decisions. For instance, in the United states, it was recently estimated that the $101 billion in combined governmental and biomedical industry enquiry funding represents nearly 5% of national wellness expenditures each year.36 In 2007, the U.S. Department of Agriculture provided more than $32 million in external research funding, representing less than one one-thousandth of 1% of annual U.S. livestock and poultry sales.37 In contrast, one single Constitute inside the National Institutes of Health—the National Institute of Allergy and Infectious Diseases—directed more than 20 times this amount to antimicrobial resistance enquiry (more than $800 1000000) in the same year.38 Given the scale of the antibiotic resistance trouble and the demonstrated role of agronomical antibiotic uses in this impending public wellness crisis, adequate back up for research specific to the role of agricultural uses of antibiotics in the development of resistance must be a national priority. Considering that the U.S. funds seventy% to 80% of biomedical inquiry worldwide, the demand for advisable levels of funding is especially acute.36
Urgently accost barriers to the collection and analysis of antimicrobial use information
Complex political, economic, and social barriers limit the quality of data on the utilise of antibiotics in food animals. Currently, such data are provided on a voluntary footing, and the methods used to collect and compile reports are not standardized or fully transparent. While voluntary industry compliance with antibody reporting is commendable, the long-term effectiveness of nonbinding auditing programs is unproven. Effective surveillance of veterinary antimicrobial production and assistants to food animals is a key beginning step toward ascertaining realistic estimates of the total telescopic of antibiotic use. These information will exist useless, yet, unless an agency with adequate analytic, regulatory, and enforcement capabilities exists. Because the commercial interests of antibiotic manufacturers must exist accordingly balanced with the public health urgency for development of new antibiotics, any agency tasked with monitoring antibiotic resistance must operate independently of commercial influences when releasing data to the public and drafting evidence-based regulations to safeguard homo wellness.
CONCLUSION
It is evident that at present, the resources devoted to studying the role of antibiotic employ in food animals—both in terms of funding and scientific enquiry—are bereft. It is at present disquisitional that agricultural use of antibiotics be recognized as one of the major contributors to the evolution of resistant organisms that consequence in life-threatening human infections and included as part of the strategy to control the mounting public health crisis of antibiotic resistance.
Footnotes
During portions of this project, Dr. Landers was supported by a training grant from the National Institute of Nursing Research, National Institutes of Health (Training in Interdisciplinary Research to Reduce Antimicrobial Resistance; T90 NR010824).
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