Overview of issues pertaining to the manufacture, distribution, and use of antimicrobials in animals and other information relevant to animal antimicrobial use data collection in the United States

This paper provides condensed literature review and contextual information concerning antimicrobial use in animals and antimicrobial use data collection techniques. Information is summarized into the following topics: (I) antimicrobial use for animal growth promotion; (II) regulatory framework for approval of veterinary antimicrobials and feed additives in the United States; (III) animal health product manufacturing and distribution networks; (IV) existing estimates of animal antimicrobial use in the United States; (V) additional sources for animal use data in the United States; (VI) recommendations from international expert groups; (VII) animal antimicrobial use surveillance systems in other nations and (VIII) human use data collection systems in the United States.     

The relationship among current management systems, production, disease and drug usage on Ontario dairy farms

The study involved 110 randomly selected dairy farms located in the Ontario, Canada counties of Bruce, Grey, Huron, Oxford, Perth, Waterloo and Wellington. Herds were classified as "intensive" and "extensive". On extensive farms, data were collected at the herd level only, while on intensive farms, data were recorded at both the individual animal and herd level. Data collection continued for approximately two and one-half years. At each visit, technicians collected production data from the most recent production recording scheme report and from the "daily log" maintained by each producer. As well as the ongoing data collection procedures, a number of supplementary data collections were made. The average 305 day milk production increased gradually during the three calendar years from 6224.6 kg in 1981 to 6443.7 kg in 1983. The average calving interval was stable at 13.2 months for all three years. The majority of cows removed from the herds were culled for beef (0.243 per animal year). The next highest removal rate was for domestic sale, followed by death, export sale and destroyed. The highest disease rate, for those conditions whose rates were based on calving, was for retained placenta (0.09 per calving), while clinical mastitis was highest for those conditions whose rates were based on animal years (0.37 per animal year). The overall crude antimicrobial dosage rate, that is, including any antimicrobial used for either prophylactic or therapeutic purposes, was 3.85 doses per animal year. The rate for therapeutic purposes only was 3.6 doses per animal year. Penicillin/streptomycin was used most often with a rate of 1.45 doses per animal year.     

Stakeholder position paper: companion animal veterinarian

The total quantity of use in companion animals is generally believed to be relatively small in comparison with antimicrobial use in food animals. Use in companion animals is principally for treatment, whereas the greater proportion of use in food animals is for prophylaxis, metaphylaxis and growth promotion. Therefore, it is important to collect data on end use in companion animals so that overall estimates of use in companion animals can be generated and separated from estimates for food animals. However, data from antimicrobial use in companion animals are extremely limited and no serious attempts to collect such data have ever been made in the United States. The lack of usage data in is concomitant with the dearth of information on antimicrobial resistance in companion animals. Companion animals have been involved in the transmission to humans of, or become infected with, foodborne zoonotic bacteria such as Salmonella and Campylobacter. Companion animals are an integral part of the ecology of antimicrobial resistance through their contact with food animals and exposure to antimicrobials for disease treatment and through contact with humans and the environment. In the practice of companion animal medicine, antimicrobial use data are important for understanding the potential impact on companion animal heath posed by antimicrobial resistance transferred from food animals, humans and the environment, and the threat to humans and other companion animals posed by antimicrobial use in companion animals. Basic information on the patterns and quantities of antimicrobial use in combination with resistance surveillance data, could help companion animal veterinarians understand the potential for development, or evidence of, an antimicrobial resistance problem in their practices, the role of companion animals in the overall epidemiology of antimicrobial resistance, and for comparison with local, regional, or national data. The combination of data from either a sentinel site system of clinics or a use survey with national data from the pharmaceutical industry should provide sufficient data to credibly estimate the total volume and patterns of antimicrobial use in companion animal medicine. The time and effort for use monitoring or to complete a survey would likely become burdensome. Practice management software now utilized at most companion animal clinics could be used to generate antimicrobial use data as well as patient population data as surrogate for the true population at risk for patient encounters in a companion animal practice.     

Public health and policy

Antimicrobial agent usage data are essential for focusing efforts to reduce misuse and overuse of antimicrobial agents in food producing animals because these practices may select for resistance in bacteria of animals. Transfer of resistant bacteria from animals to humans can lead to human infection caused by resistant pathogens. Resistant infections can lead to treatment failures, resulting in prolonged or more severe illness. Multiple World Health Organization (WHO) reports have concluded that both antimicrobial resistance and antimicrobial usage should be monitored on the national level. The system for collecting antimicrobial usage data should be clear and transparent to facilitate trend analysis and comparison within and among countries. Therapeutic, prophylactic and growth promotion use should be recorded, along with route of administration and animal species and/or production class treated. The usage data should be compared to resistance data, and the comparison should be made available in a timely manner. In the United States, surveillance of antimicrobial resistance in foodborne bacteria is performed by the National Antimicrobial Resistance Monitoring System (NARMS) for enteric bacteria, however, the United States still lacks a mechanism for collecting antimicrobial usage data. Combined with antimicrobial resistance information from NARMS, antimicrobial usage data will help to direct education efforts and policy decisions, minimizing the risk that people will develop antimicrobial resistant infections as a result of eating food of animal origin. Ultimately mitigation strategies guided by usage data will be more effective in maintaining antimicrobial drugs for appropriate veterinary use and in protecting human health.     

Evaluation of pathways for release of Rift Valley fever virus into domestic ruminant livestock, ruminant wildlife, and human populations in the continental United States

OBJECTIVE: To evaluate the feasibility for Rift Valley fever virus (RVFV) to enter the continental United States by various routes as well as to identify states in which domestic and wild ruminant and human populations would be most vulnerable to exposure to RVFV. STUDY DESIGN: Pathways analysis. SAMPLE POPULATION: Animals, commodities, and humans transported from RVFV-endemic countries to the continental United States between 2000 and 2005. PROCEDURES: Initially, agent, host, and environmental factors important in the epidemiologic aspects of RVFV were used to develop a list of potential pathways for release of RVFV into the continental United States. Next, the feasibility of each pathway was evaluated by use of data contained in governmental and public domain sources. Finally, entry points into the continental United States for each feasible pathway were used to identify the domestic and wild ruminant and human populations at risk for exposure to RVFV. RESULTS: Feasible pathways for entry of RVFV into the continental United States were importation of RVFV-infected animals, entry of RVFV-infected people, mechanical transport of RVFV-infected insect vectors, and smuggling of live virus. CONCLUSIONS AND CLINICAL RELEVANCE: Domestic ruminant livestock, ruminant wildlife, and people in 14 states (Alabama, California, Florida, Georgia, Maine, Maryland, Massachusetts, Minnesota, New Jersey, New York, Pennsylvania, South Carolina, Texas, and Virginia) appeared to be most vulnerable to exposure to RVFV. Pathways analysis can provide the requisite information needed to construct an effective targeted surveillance plan for RVFV to enable rapid detection and response by animal health and public health officials.     

EXTENSION EDUCATION SYMPOSIUM: The future of biosecurity and antimicrobial use in livestock production in the United States and the role of extension1

As the global population continues to grow, food needs will increase as well. The amount of land and other resources devoted to agriculture production is not expected to grow significantly, leading most to agree that the substantial increases in food production to meet food security needs will come through the development of technologies that improve production efficiency. Diseases are constant threats to efficiency in all segments of agriculture. In livestock production, many of the bacterial pathogens that infect food animals are controlled through the use of antimicrobials. Antimicrobials are currently used in the United States not only to treat specific diseases, but also as feed additives to prevent bacterial disease in general or to improve growth performance. In recent years, there have been several proposals in the United States, both at state and federal levels, aimed at curtailing or dramatically reducing the use antimicrobials as feed additives, creating a policy similar to that of the European Union. Here we review the current policies on antimicrobial use in the European Union and their impact on food animal production. In addition, we discuss the future of antimicrobial use in food animal production in the United States and the increasing role of biosecurity programs. Finally, we discuss the role of Cooperative Extension Service in creating improved biosecurity programs and extension programs that provide policy makers and voters information on modern food animal production practices and technologies so that policies and regulations are effective and appropriate.     

Attitudes, procedures, and delivery of behavior services by veterinarians in small animal practice

OBJECTIVE: To survey veterinarians in small animal practice concerning their attitudes about delivery of behavior services, frequency of common behavior problems, manner in which services were provided, confidence in their clinical ability to treat these behavior problems, frequency of use of pharmacologic intervention, and number of dogs and cats euthanatized specifically because of behavior problems. DESIGN: Cross-sectional mail survey. SAMPLE POPULATION: Random sample of veterinarians in small animal practice in the United States. PROCEDURE: A self-administered mail survey was sent to a random sample of 2,000 veterinarians. Results were tabulated and statistically analyzed. RESULTS: It was estimated that approximately 224,000 dogs and cats were euthanatized annually in small animal veterinary practices in the United States because of behavior problems. Although veterinarians seemed unwilling to euthanatize animals for behavior problems solely on the basis of a client's request, many veterinarians did not routinely inquire about animal behavior and often were not confident in their clinical skills to treat behavior problems. Female veterinarians tended to be more proactive in addressing behavior problems and to have more positive attitudes than male veterinarians about the importance of animal behavior. CONCLUSIONS AND CLINICAL RELEVANCE: Efforts are needed to increase the number of veterinarians who systematically incorporate inquiries about animal behavior into routine clinical practice and to build the confidence of veterinarians for diagnosing and treating animal behavior problems.     

An original system for the continuous monitoring of antimicrobial use in poultry production in France

Data collection at the flock level on a continuous basis, for antimicrobial use surveillance purposes, provides a complex challenge. Using existing on-farm records, produced as part of the regulations for meat inspection, a sampling scheme was implemented to collect on a simple, representative and continuous basis, the forms providing history of antimicrobial consumption of poultry flocks slaughtered in Brittany. Relational database-stored information provided by the forms includes treatment purpose, antimicrobial drug administered, age at treatment and treatment duration. The aim of this study was to collect information describing antimicrobial drug use quantitatively and qualitatively, by computing the frequency of antimicrobial use according to species, therapeutic class, treatment purpose, duration, and animal age at treatment. A study was carried out to check the validity of farmers' declarations. Examples of data and results are presented such as the relative importance of the different antimicrobial classes in relation to the live weight treated, which shows that beta-lactams and tetracyclines are the main classes used in broilers and turkeys respectively. Average bird weight at treatment was 0.5 kg for a broiler and 3 kg for a turkey. Nevertheless, several 'at-risk' periods could be identified. Initial results after 1 year of data collection showed that this surveillance system provides valid, detailed and useful data about antimicrobial drug use in poultry production at a low cost and with only a moderate time involvement.     

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.     

Antimicrobial drug use and resistance in dogs

Fifteen years (1984-1998) of records from a Veterinary Teaching Hospital were analyzed to determine whether antimicrobial drug resistance in coagulase-positive Staphylococcus spp. (S. aureus, S. intermedius) isolated from clinical infections in dogs has increased, and whether there has been a change in the species of bacteria isolated from urinary tract infections in dogs. In coagulase-positive Staphylococcus spp., a complex pattern showing both increases and decreases of resistance to different classes of antimicrobial drugs was observed, reflecting the changing use of different antimicrobial drug classes in the hospital over a similar period (1990-1999). In canine urinary tract infections identified from 1984 to 1998, an increase in the incidence of multiresistant Enterococcus spp. was apparent, with marginal increases also in incidence in Enterobacter spp. and in Pseudomonas aeruginosa, both of which, like Enterococcus spp., are innately antimicrobial-resistant bacteria. A survey of directors of veterinary teaching hospitals in Canada and the United States identified only 3 hospitals that had any policy on use of "last resort" antimicrobial drugs (amikacin, imipenem, vancomycin). Evidence is briefly reviewed that owners may be at risk when dogs are treated with antimicrobial drugs, as well as evidence that some resistant bacteria may be acquired by dogs as a result of antimicrobial drug use in agriculture. Based in part on gaps in our knowledge, recommendations are made on prudent use of antimicrobial drugs in companion animals, as well as on the need to develop science-based infection control programs in veterinary hospitals.     

Survey of antimicrobial susceptibility testing practices of veterinary diagnostic laboratories in the United States

OBJECTIVE: To describe antimicrobial susceptibility testing practices of veterinary diagnostic laboratories in the United States and evaluate the feasibility of collating this information for the purpose of monitoring antimicrobial resistance in bacterial isolates from animals. DESIGN: Cross-sectional study. PROCEDURES: A questionnaire was mailed to veterinary diagnostic laboratories throughout the United States to identify those laboratories that conduct susceptibility testing. Nonrespondent laboratories were followed up through telephone contact and additional mailings. Data were gathered regarding methods of susceptibility testing, standardization of methods, data management, and types of isolates tested. RESULTS: Eighty-six of 113 (76%) laboratories responded to the survey, and 64 of the 86 (74%) routinely performed susceptibility testing on bacterial isolates from animals. Thirty-four of the 36 (94%) laboratories accredited by the American Association of Veterinary Laboratory Diagnosticians responded to the survey. Laboratories reported testing > 160,000 bacterial isolates/y. Fifty-one (88%) laboratories reported using the Kirby-Bauer disk diffusion test to evaluate antimicrobial susceptibility; this accounted for 65% of the isolates tested. Most (87%) laboratories used the NCCLS (National Committee for Clinical Laboratory Standards) documents for test interpretation. Seventy-five percent of the laboratories performed susceptibility testing on bacterial isolates only when they were potential pathogens. CONCLUSIONS: The veterinary diagnostic laboratories represent a comprehensive source of data that is not easily accessible in the United States. Variability in testing methods and data storage would present challenges for data aggregation, summary, and interpretation.     

Survey of complications and antimicrobial use in equine patients at veterinary teaching hospitals that underwent surgery because of colic

OBJECTIVE: To determine current practices regarding use of antimicrobials in equine patients undergoing surgery because of colic at veterinary teaching hospitals. DESIGN: Survey. SAMPLE POPULATION: Diplomates of the American College of Veterinary Surgeons performing equine surgery at veterinary teaching hospitals in the United States. PROCEDURE: A Web-based questionnaire was developed, and 85 surgeons were asked to participate. The first part of the survey requested demographic information and information about total number of colic surgeries performed at the hospital, number of colic surgeries performed by the respondent, and whether the hospital had written guidelines for antimicrobial drug use. The second part pertained to nosocomial infections. The third part provided several case scenarios and asked respondents whether they would use antimicrobial drugs in these instances. RESULTS: Thirty-four (40%) surgeons responded to the questionnaire. Respondents indicated that most equine patients undergoing surgery because of colic at veterinary teaching hospitals in the United States received antimicrobial drugs. Drugs that were used were similar for the various hospitals that were represented, and for the most part, the drugs that were used were fairly uniform irrespective of the type of colic, whereas the duration of treatment varied with the type of colic and the surgical findings. The combination of potassium penicillin and gentamicin was the most commonly used treatment. CONCLUSIONS AND CLINICAL RELEVANCE: Results of this study document the implementation of recommendations by several authors in veterinary texts that antimicrobial drugs be administered perioperatively in equine patients with colic that are undergoing surgery. However, the need for long-term antimicrobial drug treatment in equine patients with colic is unknown.     

Dosing equine antimicrobials: Ensuring clinical success and avoiding antimicrobial resistance

Underdosing of equine antimicrobials is a global issue and may be contributing to antimicrobial resistance in horses. Recent research in Australia has identified that most antimicrobial use in peer-reviewed literature is at a higher dose than that currently on the label for many common equine antimicrobials in the United States, the UK and Australia. These dosing regimens used are now considered the most appropriate doses to be using in horses and veterinarians treating equine patients should be aware of the contemporary dosing regimens.     

West Nile virus: lessons from the 21st century

Introduction: West Nile virus (WNV) first appeared in the United States in 1999, causing illness and death in birds, horses, and humans. While the initial outbreak of this sometimes deadly viral disease was limited to the northeastern United States, the virus had an inexorable migration across the continental United States over the next 3 years, causing huge losses among the affected species. The purpose of this review is to present currently available information regarding the epi‐demiology, diagnosis, treatment, and prevention of WNV infection. Veterinarians, particularly those in an emergency practice, serve as an important source of reliable information regarding this disease for animal owners and the public in general. Data sources: Data sources used for the preparation of this review include computer‐based searches of PubMed and Commonwealth Agricultural Bureaux (CAB) abstracts. A search in PubMed using ‘West Nile’ retrieved 1468 ‘hits’ or references, while a similar search in CAB abstracts produced 815 references. Additional information was obtained from various meeting proceedings, particularly data presented in abstract form, and from the Centers for Disease Control (CDC) website dedicated to WNV. Human data synthesis: Prior to the mid‐1990s, reported large‐scale epidemics of WNV infection in humans predominantly presented as acute, mild, febrile disease, sometimes associated with lymphadenopathy and skin rash. The recent large epidemic in the United States, in contrast, has prominently featured encephalitis, particularly among the elderly. Additionally, polio‐encephalomyelitis‐like complications resulting in long‐term neurologic sequelae have been reported. There are many WNV‐permissive native avian and mosquito hosts in the Unites States and there appear to be few limitations to the spread of the disease in the United States. It is expected that the virus will be identified in all 48 continental states, Mexico, and Canada by the end of 2003. Veterinary data synthesis: The horse is the animal species most affected by the recent WNV epidemic in the United States, and losses to the equine industry have been large and unprecedented. A United States Department of Agriculture (USDA)‐approved vaccine against WNV has been in use in horses since 2001 and appears to be effective in limiting the incidence of disease in well‐vaccinated populations. WNV infection has been documented in other species of mammals, including camelids (alpaca/llamas) and dogs, and veterinarians should include WNV as a differential diagnosis for animals presenting with clinical signs consistent with central nervous system infection. A large concern exists for endangered bird populations, particularly birds of prey, whether in zoos or in the wild.     

Environmental surveillance for Salmonella enterica in a veterinary teaching hospital

OBJECTIVE: To evaluate the extent of environmental contamination with Salmonella enterica in a veterinary teaching hospital. DESIGN: Longitudinal study. SAMPLES: Environmental samples obtained from 69 representative locations within a veterinary teaching hospital by use of a commercially available electrostatic wipe. PROCEDURE: Environmental samples were obtained for bacteriologic culture, and antimicrobial susceptibility testing was performed on each environmental isolate. Environmental isolates were compared with isolates obtained from animals during the same period to investigate potential sources of environmental contamination. RESULTS: 54 S. enterica isolates were recovered from 452 (11.9%) cultured environmental samples. Five different serotypes were recovered; the most common serotypes were S. Newport and S. Agona. Within the 5 serotypes recovered, 10 distinguishable phenotypes were identified by use of serotype and antimicrobial susceptibility patterns. Of the environmental isolates, 41 of 54 (75.9%) could be matched to phenotypes of isolates obtained from animal submissions in the month prior to collection of environmental samples. CONCLUSIONS AND CLINICAL RELEVANCE: Results indicated that environments in veterinary hospitals can be frequently contaminated with S. enterica near where infected animals are managed and fecal specimens containing S. enterica are processed for culture in a diagnostic laboratory. Bacteriologic culture of environmental samples collected with electrostatic wipes is an effective means of detecting contamination in a veterinary hospital environment and may be beneficial as part of surveillance activities for other veterinary and animal-rearing facilities.     

Farming strategies in organic dairy farming: Effects on breeding goal and choice of breed. An explorative study

Organic farming principles give rise to multifunctionality: different activities are combined at farm level to create ecological and economic synergies. These principles do however allow for different operationalisations and different farm development strategies, for example with regard to the use of external inputs or the decision whether or not to use advanced breeding technologies such as artificial insemination. Maintaining and improving diversity are therefore characteristic to organic farming. Since organic farming took off in the early 1990 s, many specialised dairy farms which tend to be more mono-functional in nature, have converted to organic, adding a new farming strategy to the diverse collection of farming strategies in organic dairy farming. All these farming strategies actually create different organic production environments for cows, which might result in different demands on selective breeding and breeding technology. This differential demand was explored in a survey, among 151 organic dairy farmers, on general farm strategy, milk production, breeding goal, choice of breed and approach to reproduction. Farmers were divided into one of two groups on each of three strategic options: a) diversification in farm business—Specialised Dairy Farming vs. Multifunctional Farming; b) intensity of milk production—Low Input vs. High Input Farming and c) naturalness of breeding—Farming with Artificial Insemination vs. Farming with Natural Service.A pair-wise comparison within each strategic option showed that each pair differed significantly with regard to farm characteristics, farm goal and animal production goals. However, there were only minor or no significant differences within each pair with regard to overall breeding goal. For each strategic option, big differences were found within each pair as regards preferred cattle breeds and crossbreeds. Farmers in the Specialised Dairy Farming and High Input Farming groups preferred milk-type cattle (Holstein and Holstein crossbreeds), while farmers in the Multifunctional Farming and Low Input Farming groups preferred various native Dutch breeds. But even farmers with a similar strategy (within one group) differed strongly in their choice of breeds and crossbreeds. These results indicate that organic farmers are going through process of learning by doing, experimenting as they search for breeds or crossbreeds that are optimally suited to their farm environment and that best agree with their farm development strategy. In this, the growing preference for keeping bulls on the farm for natural service is remarkable.     

Reportable animal diseases in the United States

Timely reporting of animal diseases is fundamental to the detection of emerging threats, rapid and effective outbreak response, and ultimately the health of both animals and humans. In the United States, each state has the authority to regulate reporting of diseases. While past research has reviewed reportable human diseases, the research on reportable animal diseases has assessed only veterinarian knowledge and understanding of law rather than identifying the actual statutes and regulation that exists. Therefore, this article reviewed the statutes, regulations, and online reportable animal disease lists from the 50 states and District of Columbia to describe the legal landscape of animal disease reporting. The findings suggest wide variation in state animal disease reporting requirements. Three hundred and forty distinct diseases, agents, and categories were identified, with only 15 diseases being listed by 40 or more states. States typically require reporting of animal diseases within 48 h. Substantial consideration needs to be given to the implications of these variations for rapid and effective animal and zoonotic disease detection and reporting in the United States, particularly in light of One Health initiatives and international obligations.     

Stakeholder position paper: economist's perspectives on antibiotic use in animals

Economics seeks to understand and explain the allocation of resources within society and to suggest appropriate policy to achieve goals such as optimal efficiency. Relating antimicrobial use and antibiotic resistance is a complex task and requires very clear and careful analyses of many relationships. To address these relationships, antibiotic use data must be linked with other basic data. Ideally, a complex relational database needs to be developed. These must include data on: antimicrobial usage, farm-level animal productivity, basic disease, basic farm management, consumer response, and antimicrobial resistance at multiple levels (farm, during process, on a variety of both animal, vegetable and grain-derived food products, from humans, from other animal species, and from the environment) among other data. Such a complex relational database can help with the attribution and risk assessment process. Also these linked data are needed in order to develop the economic production models and other economic models, as well as control for confounding so that there is both adequate and appropriate statistical control. Antimicrobial usage data may become economically important for reasons unrelated to animal productivity and animal health. With expanding global trade of animals and animal products, there have been changes in restrictions and regulations associated with the movement of products. Future trade opportunities may be linked to antimicrobial usage. The European Union banned the use of antimicrobials for growth-promoting purposes based on perceived risk and on public opinion. Monitoring antimicrobial use, disease occurrence, and resistance patterns following changes in usage that are a result of either policy changes or response to new information will help in the understanding of the complex relationships in microbial and disease ecology. There is a lot of evidence substantiating the productivity and profitability gains to producers from the use of antimicrobials. There is also evidence for the potential gains to consumers, both from an economic perspective as well as from a health perspective. Economists can help identify the implications of these relationships both at a micro- and macro-economic level; both relative to producer and to consumer welfare. We are at a pivotal time in history with sufficient analytical expertise and tools to address this complex issue from a scientific perspective. Linking various agencies so there can be coordination of data collection and data sharing is needed to successfully address this topic.