Use Of Antimicrobials In Animals Research Articles

Deliberations of an Advisory Committee regarding priorities, sources, and methods for collecting animal antimicrobial use data in the United States

This paper describes the methodological options for food animal antimicrobial use data collection in the United States, including data priorities, methods, and limitations that were identified by a diverse group of expert stakeholders. Four major categories of antimicrobial use data were identified based on the source of information and its proximity to actual use: end-user data, prescription data, manufacturing data, and distribution data. Criteria were developed to aid in evaluating the overall utility of each methodological option, and an attempt was made to develop a qualitative, composite “overall usefulness” score for each option. Concensus was not reached on option scores, therefore, the experts individually rated six methodological options relative to the evaluation criteria, and provided comments and rationale for each response. The responses serve as a microcosm of the issues and stakeholder perspective: most relevant to animal antimicrobial use data collection in the United States.

Animal health pharmaceutical industry

The animal health pharmaceutical industry has proactively reported on the volumes of member company antimicrobial active ingredients sold in the U.S. At the individual company level, reporting of finished product distribution data to the FDA is a regulatory requirement, with applications to surveillance and pharmacovigilance. An accounting of product manufactured is done for purposes of good business practices, as well as marketing analyses. Additional applications of antimicrobial usage data might include use in risk assessments, such as for the FDA's Center for Veterinary Medicine Guidance for Industry #152 for the evaluation of the microbiological safety of antimicrobials intended for use in food animals. Compilation of national usage data will be a complex undertaking, hindered by issues such as confidentiality, auditing, field use practice variations, population dynamics (e.g. disease incidence, market conditions for poultry and livestock production), and generic usage. The amounts or volumes in pounds should be considered relative to the large number of animals under husbandry in the United States. Large volumes might seem impressive unless put into proper context. Until such time as a clearly defined application of national usage data is agreed, it is recommended that local usage programs will provide more useful information to perpetuate prudent antimicrobial use in animals.

Stakeholder position paper: The need for antimicrobial use data for risk assessment

Risk assessment seeks to estimate the probability and impact of human health effects due to antimicrobial resistance arising from antimicrobial use in animals. Potential ecological pathways for the flow of antimicrobial resistant bacteria and resistance determinants through the food supply and environment are diverse and complicated and this has been a logistical barrier to direct epidemiological measure of risk. Consequently, a number of indirect approaches to assessment have been developed. This paper provides some examples of risk assessments that have been conducted with and without antimicrobial use data, and identifies possible benefits and applications of quantitative antimicrobial use data for risk assessment.

Stakeholder position paper: Epidemiological perspectives on antibiotic use in animals

Epidemiologists studying antimicrobial resistance are often interested in analyzing the association between antimicrobial resistance and antimicrobial use in animals, and on the impact of antimicrobial use in animals on the occurrence of resistance in bacteria affecting human populations. Given the various potential antimicrobial use data sources, it seems likely there will be some variability in the utility of the data for interpreting trends in antimicrobial resistance and investigating the relationship between antimicrobial use in animals and antimicrobial resistance in bacteria affecting human health. From an epidemiologic perspective, the major issues related to incorporation of antimicrobial use data into antimicrobial resistance monitoring programs are the further development of epidemiologic methods for collecting, quantifying, analyzing and interpreting use data; an open and realistic consideration of the limitations of the data; developing an understanding of scaling, temporal and spatial heterogeneity issues; and the interpretative problems of ecologic and atomistic fallacy. Given the many potential biases in antimicrobial use data, attempts to relate levels of antimicrobial use to levels of antimicrobial resistance should be done with caution until the data are better understood and the aforementioned issues have been addressed.

Impact of Antimicrobial Use in Animals and Regulatory Response

There is accumulating evidence that the use of antimicrobials in food-producing animals has adverse human health consequences. The use of these drugs in food animals selects for resistant pathogens and resistance genes that may be transferred to humans through the consumption or handling of foods of animal origin. Recent studies have demonstrated that antimicrobial resistance among foodborne bacteria may cause excess cases of illness, prolonged duration of illness, and increased rates of bacteremia, hospitalization and death.
 The US Food and Drug Administration (FDA) is committed to resolving the public health impact arising from the use of antimicrobial drugs in food-producing animals. The FDA's goal is to ensure that significant human antimicrobial therapies are not compromised or lost while providing for the safe use of antimicrobials in food animals. The FDA published a guidance document titled "Evaluating the Safety of Antimicrobial New Animal Drugs with Regard to their Microbiological Effects on Bacteria of Human Health Concern" that outlines a pathway drug sponsors can use to address concerns about antimicrobial resistance prior to approval of their drug. 30 The process uses a qualitative risk assessment approach to assess the potential of the intended use of a product to develop resistance in bacteria that may harm humans. The level of risk determines the level of risk management that is required for the drug to be approved.

Identification and surveillance of antimicrobial resistance dissemination in animal production

Antimicrobial resistance is a growing problem in human medicine, and concern has been expressed that use of antimicrobials in animals may be a contributing factor. Although the majority of human pathogens showing antibiotic resistance have no link with animals, the issue of animal use of antimicrobials remains controversial, particularly with respect to antibiotic growth promoters (AGP). The European Union (EU) has withdrawn as AGP some compounds that remain in use in the United Sates. This difference in availability allows comparisons to be made of antimicrobial resistance outcomes with and without use of an AGP. Such comparisons so far show little apparent measurable benefit to human health resulting from the EU removal of AGP, and there is evidence of increased use of therapeutic antibiotics in animals to treat an apparent increased incidence of clinical disease. Microbial risk assessments are important in judging quantitatively or qualitatively whether the risk of using a particular AGP is acceptable in terms of potential hazard to human health. Resistance surveillance is an essential part of such microbial risk assessments, but such surveillance should be carefully planned to avoid confounding factors that could invalidate any conclusions.

Bayesian Monte Carlo Uncertainty Analysis of Human Health Risks from Animal Antimicrobial Use in a Dynamic Model of Emerging Resistance†

Recent qualitative analyses warn of potential future human health risks from emergence of antibiotic resistance in food-borne pathogens due to the use of similar antimicrobial drugs in both food animals and human medicine. While historical data suggest that human health risks from some animal antimicrobials, such as virginiamycin (VM), have remained low (McDonald et al., 2001), there is a widespread concern that "resistance epidemics" or endemics could arise in the future. How reassuring is the past about the future? This article applies quantitative risk assessment methods to help find out, using human health risks from VM and the nearly identical human antimicrobial quinupristin-dalfopristin (QD) as a case study. A dynamic simulation model is used to predict the risks of emerging resistance to human antimicrobials in human populations from given input assumptions. Bayesian Monte Carlo uncertainty analysis allows past data to constrain and inform selection of input parameter values, and thus to predict the possible future resistance patterns that are consistent with historical data. The results show that health risks from VM use in food animals are highly sensitive to the human prescription rate of QD. For realistic prescription rates, quantitative risks are less than 1 x 10(-6) even for members of the most-threatened (ICU patient) population, while societal risks are <1 excess statistical death per year for the whole U.S. population. Such quantitative estimates complement more qualitative assessments that discuss the possibility of future "resistance epidemics" (or endemics) without quantifying their probabilities.

Antimicrobial resistance in food.

Antimicrobial resistance in food.

Observations on the history of the development of antimicrobials and their use in poultry feeds

Antimicrobials are powerful tools, but controversy and conflict often follow power. The development of antimicrobials was marked by personal attacks, political intrigue, internal conflicts, and lawsuits. Such controversy and conflict has continued. The early history of supplementing animal feeds with antimicrobials parallels the isolation and identification of vitamin B12. Vitamin B12 was isolated and characterized in 1948, but further research showed that several feed ingredients, including dried mycelia of certain fungi, were more potent as growth promoters in the diet of chicks than was vitamin B12 alone. The growth-promoting component in fungal mycelia was shown to have antimicrobial activity. A total of 32 antimicrobial compounds are approved for use in broiler feeds in the U.S. without a veterinary prescription. Fifteen compounds are listed for treatment of coccidiosis, 11 are listed as growth promotants, and six are listed for other purposes. Seven compounds are also used in human medicine. These compounds include bacitracin, chlotetracycline, erythromycin, lincomycin, novobiocin, oxytetracycline, and penicillin. No published estimates of antimicrobial use in animals exist at present, and estimates of that use differ markedly. The Union of Concerned Scientists (UCS) estimates usage at 30.6 million pounds, nearly 50% (49.85%) higher than the Animal Health Institute (AHI) estimate of 20.42 million pounds. AHI surveyed their members (the manufacturers of antimicrobials) to obtain their estimates, whereas USC calculated their estimates using published data and the following general formula: antimicrobial use = number of animals treated x average days treated x average dose.

From the Farm to the Kitchen Table: the Negative Impact of Antimicrobial Use in Animals on Humans

Antimicrobials used as growth promotion agents in the livestock and poultry industries appear to result in the spread of drug-resistant pathogens to humans such as vancomycin-resistant enterococci, fluoroquinolone-resistant Campylobacter jejuni, and multidrug-resistant strains of Salmonella enterica. We present some epidemiologic evidence supporting this link and suggest that the use of antimicrobial agents for nontherapeutic purposes in food animals should be severely limited, if not banned altogether.

THE FOOD SAFETY PERSPECTIVE OF ANTIBIOTIC RESISTANCE

ABSTRACT Bacterial antimicrobial resistance in both the medical and agricultural fields has become a serious problem worldwide. Antibiotic resistant strains of bacteria are an increasing threat to animal and human health, with resistance mechanisms having been identified and described for all known antimicrobials currently available for clinical use. There is currently increased public and scientific interest regarding the administration of therapeutic and sub-therapeutic antimicrobials to animals, due primarily to the emergence and dissemination of multiple antibiotic resistant zoonotic bacterial pathogens. This issue has been the subject of heated debates for many years, however, there is still no complete consensus on the significance of antimicrobial use in animals, or resistance in bacterial isolates from animals, on the development and dissemination of antibiotic resistance among human bacterial pathogens. In fact, the debate regarding antimicrobial use in animals and subsequent human health implications has been going on for over 30 years, beginning with the release of the Swann report in the United Kingdom. The latest report released by the National Research Council (1998) confirmed that there were substantial information gaps that contribute to the difficulty of assessing potential detrimental effects of antimicrobials in food animals on human health. Regardless of the controversy, bacterial pathogens of animal and human origin are becoming increasingly resistant to most frontline antimicrobials, including expanded-spectrum cephalosporins, aminoglycosides, and even fluoroquinolones. The lion's share of these antimicrobial resistant phenotypes is gained from extra-chromosomal genes that may impart resistance to an entire antimicrobial class. In recent years, a number of these resistance genes have been associated with large, transferable, extra-chromosomal DNA elements, called plasmids, on which may be other DNA mobile elements, such as transposons and integrons. These DNA mobile elements have been shown to transmit genetic determinants for several different antimicrobial resistance mechanisms and may account for the rapid dissemination of resistance genes among different bacteria. The increasing incidence of antimicrobial resistant bacterial pathogens has severe implications for the future treatment and prevention of infectious diseases in both animals and humans. Although much scientific information is available on this subject, many aspects of the development of antimicrobial resistance still remain uncertain. The emergence and dissemination of bacterial antimicrobial resistance is the result of numerous complex interactions among antimicrobials, microorganisms, and the surrounding environments. Although research has linked the use of antibiotics in agriculture to the emergence of antibiotic-resistant foodborne pathogens, debate still continues whether this role is significant enough to merit further regulation or restriction.

Antimicrobial use and resistance in animals.

Food animals in the United States are often exposed to antimicrobials to treat and prevent infectious disease or to promote growth. Many of these antimicrobials are identical to or closely resemble drugs used in humans. Precise figures for the quantity of antimicrobials used in animals are not publicly available in the United States, and estimates vary widely. Antimicrobial resistance has emerged in zoonotic enteropathogens (e.g., Salmonella spp., Campylobacter spp.), commensal bacteria (e.g., Escherichia coli, enterococci), and bacterial pathogens of animals (e.g., Pasteurella, Actinobacillus spp.), but the prevalence of resistance varies. Antimicrobial resistance emerges from the use of antimicrobials in animals and the subsequent transfer of resistance genes and bacteria among animals and animal products and the environment. To slow the development of resistance, some countries have restricted antimicrobial use in feed, and some groups advocate similar measures in the United States. Alternatives to growth-promoting and prophylactic uses of antimicrobials in agriculture include improved management practices, wider use of vaccines, and introduction of probiotics. Monitoring programs, prudent use guidelines, and educational campaigns provide approaches to minimize the further development of antimicrobial resistance.

Epizootiological and microbiological methodologies for monitoring anti-microbial resistance among enterobactericeae of animal origin: a review

The emergence of anti-microbial resistant strains in the treatment of bacterial infections has demanded some critical revaluation of the continued use of these agents in agriculture. Current information on the spread of pathogenic and commensal bacteria of animal origin and their resistance genes highlight the existence of interactions between micro-ecological systems in different animal hosts and the environment. Protocols for appropriate epizootiological investigations of anti-microbial resistance in farming environments should therefore incorporate elements of such ecologic interactions. For example, to evaluate the risks of continued use of anti-microbials in animals and their impact on human health, veterinary monitoring of bacterial susceptibility should assume a broad structure that includes a large number of animal species, detection of resistance levels in bacteria resident in animals and animal-derived foods, and also incorporate deferent bacterial species especially veterinary pathogens, zoonotic bacteria and commensals. Similarly, application of molecular typing techniques alongside conventional phenotypic methods is preferred especially when testing for newly emerging as well as established resistance patterns. KEY WORDS: Anti-microbial resistance, Enterobacteriaceae, Epizootiology, Molecular typing, Animal (Nigerian Veterinary Journal: 2002 23(2): 23-39)

Curtailing antibiotic use in agriculture: it is time for action: this use contributes to bacterial resistance in humans.

Curtailing antibiotic use in agriculture: it is time for action: this use contributes to bacterial resistance in humans.

Emergence and Transfer of Antibacterial Resistance

There is increased public and scientific interest regarding the administration of therapeutic and subtherapeutic antimicrobials to animals. This is due primarily to the emergence and dissemination of multiple antibiotic resistant zoonotic bacterial pathogens. The debate regarding antimicrobial use in animals and subsequent human health implications has been going on for over 30 yr. This was initiated by the release of the Swann report in the United Kingdom in 1969. While this issue has triggered a tremendous controversy, there is still no agreement on the significance of antimicrobial use in animals and (or) resistance in bacterial isolates from animals on the development and dissemination of antibiotic resistance among human bacterial pathogens. Contributing to the controversy is the isolation of bacterial pathogens of animal and human origin that are increasingly resistant to most frontline antibiotics, including third-generation cephalosporins, aminoglycosides, and even fluoroquinolones. Recent studies have demonstrated that the majority of these multiple antimicrobial resistant phenotypes are obtained by the acquisition of external genes that may provide resistance to an entire class of antimicrobials. A number of these resistance genes have been associated with large, transferable, extra-chromosomal DNA elements, called plasmids, on which may be other DNA mobile elements, termed transposons and integrons. These DNA mobile elements have been shown to possess genetic determinants for several different antimicrobial resistance mechanisms are largely responsible for the rapid dissemination of resistance genes among different bacterial genera and species. Although the impact of a dairy practitioner or producer may seem small with regards to the emergence and dissemination of bacterial antimicrobial resistance, it is critical that we understand the importance of appropriate antimicrobial therapy from a broader perspective in the dairy production environment.

Surveillance of antimicrobial resistance in Escherichia coli strains isolated from pigs at Spanish slaughterhouses

Antimicrobial resistance can make the efficient treatment of bacterial infections in humans and animals more difficult. Antimicrobial use in food animals may be one of the factors contributing to resistance. The Spanish surveillance network VAV has established a baseline of antimicrobial resistance in Escherichia coli strains from healthy pigs. Minimum inhibitory concentration and patterns of resistance to antimicrobials used in animals and humans were determined for 205 faecal strains isolated in a sampling frame of four slaughterhouses in Spain from 220 pigs in 1998. Higher levels of resistance were seen against antimicrobial agents authorised for use in food animals especially tetracycline, sulphonamides, trimethoprim and amoxycillin. All isolates were susceptible to antimicrobials employed mainly in humans such as ceftazidime, cefotaxime, imipenem, aztreonam and amikacin.

Antibiotic Use in Food Animals: Controlling the Human Health Impact

Resistance to antimicrobial drugs has compromised control of many bacterial pathogens. For foodborne pathogens, the most likely source of resistance is use of antimicrobials in food-producing animals. To control the human health impact from use of antimicrobials in animals, the U.S. Food and Drug Administration (FDA) recently announced plans to assess the microbial safety of all antimicrobials intended for use in food-producing animals. This paper describes the history of antimicrobial use and regulation in animals, the public health concern, the current animal drug approval process in the United States, the international perspective, and FDA's proposed procedures to evaluate the human health impact of the antimicrobial effects associated with animal drugs intended for use in food-producing animals. The primary public health goal of the improved regulatory paradigm is to ensure that significant human antimicrobial therapies are not lost due to use of antimicrobials in food animals.

Issue of Antimicrobial Use in Food Animals

The issue of antimicrobial use in food animals has been controversial for more than three decades. The Food and Drug Administration (FDA) first called for several restrictions on antimicrobial use in feed in 1977. That proposal has generated several studies and reports over the subsequent years. Definitive answers about the safety of antimicrobial use in animals remain scientifically challenging, but we are continuing to uncover more truths and, more important, have begun updating FDA's regulatory process for evaluating antimicrobial drugs intended for use in food animals.

Using Feedlot Records to Control Antimicrobial Resistance

Records are an essential component of herd health programs and beef quality assurance programs. They are used to optimize production efficiency and monitor and verify procedures for beef quality and food safety. Recently, health organizations around the world have stated that production records required to show prudent drug use by veterinarians and producers. The development of resistance in zoonotic organisms may be promoted by the inappropriate use of antimicrobials in animals. Therefore, treatment records are required to show the public that antimicrobials are used judiciously in food animal production for clinical and production efficacy, while minimizing antimicrobial resistance impacts on human health.

Antimicrobial use in animals and its consequences for human health

Antimicrobial use in animals and its consequences for human health