Even therapeutic antimicrobial use in animal husbandry may generate environmental hazards to human health.

Political attention to antimicrobial resistance (AMR) has never been greater. Governments worldwide are concerned that AMR threatens to undo modern medical achievements with the spectre of a post antibiotic era in which commonplace infections, once eminently treatable, become nontreatable causes of serious morbidity and mortality 1. With suggestions that AMR and multi-drug resistant organisms are as important as climate change and could cast the world back into the dark ages of medicine, ranking alongside terrorism as matters of national risk 2, 3, the political landscape on this subject has been clearly set. Concerns about AMR and its health impact are, of course, not new and began at almost the same time as the introduction of antimicrobials. In 1945, just after the introduction of penicillin as a therapeutic agent in humans and animals, Fleming warned in his Nobel Prize acceptance speech that misuse of antimicrobials could result in bacterial resistance. This prediction rapidly became true with the discovery of each new class of antimicrobial quickly followed by the appearance of resistance to it. By the 1960s there was widespread realisation, and acceptance in the scientific community and lay press, that antimicrobial use (and misuse) resulted in rapid selection for resistance against all classes of antimicrobials. What is new, and has changed the political and regulatory landscape for AMR completely, is the realisation that science is not able to out-pace the microbes. There have been no completely new classes of antimicrobials discovered and brought to market since the 1980s, perhaps not surprising given the relatively small range of bacterial targets and the rapid rate of antimicrobial discovery during the ‘golden age’ from the mid 1940s onwards 4. Although there are some rays of hope, for example the recently reported new compound ‘teixobactin’ 5, the pipeline for new antimicrobials is practically dry. In other words, the solutions to AMR must come from within the medical, veterinary and animal industry sectors by addressing the underlying causes of, and changing the therapeutic approaches to, infectious disease. The political and scientific view that antimicrobials can no longer be regarded as the panacea or ‘magic bullet’ capable of eradicating infectious disease is widely accepted, and it is now clear that the human and animal health care sectors need to respond accordingly. A major challenge for the politicians is that there are still significant gaps in the surveillance data required to fully understand the drivers of AMR in both humans and animals 6, 7 and, critically, to measure the effects of interventional measures to reduce AMR. It is therefore not surprising that scientific opinion continues to be divided on practically every key question about AMR except that it is now a serious global problem causing significant economic loss with welfare, morbidity and mortality impacts in humans and animals. Antimicrobial resistance is a natural phenomenon: bacteria produce antimicrobial substances as part of their repertoire to compete in the struggle for colonisation, space and nutrients. Resistance therefore existed long before the introduction of antimicrobial drugs: the effect of using antimicrobials has been to accelerate AMR through classical selective pressure. That this has happened in both veterinary and human populations of bacteria is not disputed; the evidence for interconnection of AMR in these two populations is, however, inconclusive and is the subject of continuing political and scientific debate with contradictory evidence produced by both sides 8-10. It does appear that antimicrobial use in animals increases AMR in animal bacteria and that treating people with antimicrobials increases AMR in human bacteria. However, current scientific evidence does not allow definitive assessment of whether reducing antimicrobial use in animals has reduced AMR in medical pathogens. The extent to which AMR in populations of animal bacteria threatens public health therefore remains uncertain. The evidence for resistance in animal bacteria acting as genetic reservoirs of resistance for transfer to bacteria of public health importance is also inconclusive. Even for zoonotic bacteria such as Salmonella typhimurium DT104, the links between animal and human bacterial populations have become less clear with the application of sophisticated molecular typing bacterial methods and population genetics adding new complexity to the AMR debate 11. However, the lack of conclusive evidence notwithstanding, the prevailing political and regulatory opinion continues to be that antimicrobial use, and associated AMR, in animals is a driver of AMR in medical pathogens and that controlling veterinary prescription of antimicrobials will help safeguard public health. The ongoing political and public health scrutiny of veterinary use of antimicrobials is not surprising and the assumption that veterinary antimicrobial use contributes to, or is perhaps even directly the cause of, AMR in human medicine is understandable. The fact that the classes of antimicrobials used in veterinary and human medicine are the same 12; that food-borne and other zoonotic infections provide an opportunity for transfer of resistant bacteria from animals to humans; that populations of pathogenic and nonpathogenic animal bacteria may act as genetic reservoirs of resistance for important medical pathogens, with close contact between people and companion animals, in addition to food products, providing opportunity for genetic exchange; and, perhaps most importantly from a political perspective, that in many countries around the world the total quantity (gross weight) of antimicrobials used in veterinary medicine is greater than in human medicine 13, 14, has put antimicrobial use in animals at the centre of the public health AMR debate. When combined with the use of antimicrobials for disease prevention at herd or flock level and, in around half of the world's countries, for growth promotion, it is little wonder that antimicrobial use in animals has resulted in sustained political concern over the contribution that veterinarians and the animal sector in general may be making to the growing crisis of antimicrobial resistance in humans, with frequent calls for restriction or even banning of veterinary use of antimicrobials. Despite numerous political recommendations that coordinated, overarching surveillance of AMR is implemented at national and international level 15, 16 there are still relatively few examples of harmonised and integrated surveillance in humans and animals that allow comparison of data. Examples include The National Antimicrobial Resistance Monitoring System (NARMS) in the USA, Canadian Integrated Program for Antimicrobial Resistance Surveillance (CIPARS) in Canada, Japanese Veterinary Antimicrobial Resistance Monitoring System (JVARM) in Japan and several European schemes including Danish Integrated Antimicrobial Resistance Monitoring and Research Programme (DANMAP) (Denmark), NORM-VET (Norway), Swedish Veterinary Antimicrobial Resistance Monitoring (SVARM) (Sweden) and NethMap/Monitoring of Antimicrobial Resistance and Antibiotic usage in Animals in the Netherlands (MARAN) (the Netherlands). At EU level, the European Food Safety Authority (EFSA) and the European Centre for Disease Prevention and Control (ECDC) monitor AMR in the food chain and food-borne zoonotic pathogens, but not in companion animals. In the absence of sufficient scientific evidence about AMR, in particular the key question of the impact of veterinary antimicrobial use on public health, politicians around the world have faced difficult decisions. In the absence of scientific certainty politicians have adopted the ‘precautionary principle’, allowing preventive action to be taken when there is a possibility of harm but where the scientific evidence is not sufficiently complete to allow full assessment. The result in Europe is a continuing European political focus on banning or restricting veterinary antimicrobial use, especially in the agricultural sector, and reducing the total quantities of antimicrobials used in animals. In the political and regulatory environment in the USA, the precautionary principle has been applied somewhat differently with less political appetite for banning or restricting antimicrobials 9. The first active political engagement with antimicrobial resistance occurred in 1968 in response to growing concerns over multidrug resistant Salmonella in humans and animals, with the establishment of an independent advisory committee by the UK Government chaired by Professor Michael Swann. The Swann Report 17, published in 1969, recommended restriction of the use of antimicrobials as growth promoters, which took 45 years to fully implement in Europe, and establishment of overarching monitoring of AMR in humans and animals, which has still not been implemented globally. Almost 50 years on, this report continues to set the political stage in relation to veterinary antimicrobial use and possible impacts on human health. We would do well not to lose sight of the lessons learned in the decades following its publication, specifically that sensible recommendations based on competent assessment of the available, even if incomplete, scientific evidence should not be sidelined pending collection of conclusive evidence; instead the two should progress in parallel with continuous monitoring and refinement as evidence is gathered. The global political thrust in relation to AMR in the human and animal health sectors continues to be that overuse of antimicrobials is the cause of the problem and that reducing their use is the solution. In Europe, most political effort since 1969 has been directed at the food animal sector through reducing the use of antimicrobials as growth promoters and, more recently, reducing total antimicrobial use. It was not until 2006 that a EU-wide ban on antimicrobial growth promoters was eventually implemented, completing a political process that had started four decades previously with the banning of tetracycline, penicillin and streptomycin for growth promotion in 1974, followed by complete bans of antimicrobial growth promoters in Sweden and Denmark in 1988 and 1994. Denmark also implemented restrictions on veterinary dispensing of antimicrobials; decoupling veterinary prescription of antimicrobials from supply remains on the European political agenda and, if implemented, would have significant impact on veterinary practice business models in many countries. Monitoring, and reducing, antimicrobial use has become a key global political driver. The European Medicines Agency monitors the sales of antimicrobial agents for food producing animals and horses across Europe 18 providing benchmarks against which political targets for reduction are set. In some countries governmental targets for reduction in the sales of veterinary antimicrobials have been agreed with stakeholders. For example, the Netherlands decreased sales of antimicrobials by 49% between 2010 and 2012 with further reduction targets agreed; antimicrobial sales in Scandinavia have been progressively reduced through a series of government–stakeholder agreed targets 18. Nevertheless, the estimated consumption of antimicrobials (corrected for estimated biomass) in animals continues to be greater than in humans across Europe as a whole 6. It is becoming increasingly clear, however, that the concept of overuse as the key driver of AMR may be overly simplistic 19. Antimicrobial resistance is a complex public and animal health issue and there is recognition that integrated strategies across all sectors, backed by political will, stakeholder buy-in and sufficient economic support, are required to control it 1. Although overprescribing of antimicrobials is undoubtedly an important factor, reducing their use in human medicine has not consistently resulted in reduction of resistance for key pathogen–antimicrobial combinations with examples of resistance remaining apparently stable or even increasing despite reduced antimicrobial use. The question of whether phasing out antimicrobials as growth promoters across Europe and the restrictions placed on therapeutic use of antimicrobials in Scandinavia, with associated reductions in quantities used, has resulted in a positive impact on human health continues to be the subject of scientific and political disagreement. Responsible, or ‘prudent’, use of antimicrobials has emerged as a parallel precautionary approach to the control of AMR. Initially, the political focus was on restricting veterinary use of antimicrobials used to treat multidrug resistant human pathogens presenting significant risk to public health. Since 2005 the World Health Organization has published lists of ‘critically important antimicrobials for human medicine’, ranked according their importance with the goal that their use should be restricted in all sectors to preserve their effectiveness 20. This approach has been extended by the World Organisation for Animal Health (OIE) with the publication of a list of antimicrobials of veterinary importance which contains recommendations for restricting the use in food animals of antimicrobials that are critically important for both human and animal health 21. This list includes fluoroquinolones and third- and fourth-generation cephalosporins and forms a rational basis for responsible guidelines worldwide. There are several examples of stakeholder groups at national and international level that have responded to the AMR challenge and shown leadership in producing responsible use guidelines. In the late 1990s the UK veterinary and farming sectors established the RUMA (responsible use of medicines in agriculture) alliance and in 2005 EPRUMA (European platform for responsible use of medicines in animals) was established. Stakeholder groups have now produced a variety of responsible use guidelines for antimicrobials in veterinary practice. Examples include general guidance to veterinary practitioners from the British Veterinary Association (BVA) and the Federation of Veterinarians in Europe (FVE), guidelines on antimicrobial use in companion animal practice from the Federation of European Companion Animal Veterinary Associations (FECAVA), the British Small Animal Veterinary Association (BSAVA), the American Veterinary Medical Association (AVMA) and in equine practice from the British Equine Veterinary Association (BEVA). Widespread adoption of responsible use guidelines in equine practice is an important goal, coupled with accurate recording of use (as, for example, already happens in Scandinavia), that will go some way to addressing political concerns about the prescription of critically important antimicrobials and cascade prescribing by veterinarians, including equine practitioners 22, 23. It is understandable, given the importance of food-borne zoonotic bacteria, that the political lens has thus far been focused mainly on the food animal sector. It is only recently that antimicrobial use in companion animals and horses has received political attention 7, 24 probably because comparatively small quantities (<10% of total quantities sold each year) of antimicrobials are used in these species 18 and because of a public health focus on food-borne pathogens. There are now recommendations that systematic international surveillance of AMR is established for companion animals and horses and a recognition that the close relationship between people and companion animals may provide new opportunities for transfer of resistance to human pathogens 7, 24. Antimicrobial resistance is now a highly important One Health issue with political impact squarely on companion animal and equine veterinary medicine; it is no longer a subject confined to the food animal sector. Antimicrobial resistance is, of course, also important for companion animal and equine health with multidrug resistant pathogens such as meticillin-resistant Staphylococcus aureus (MRSA) causing clinical disease in horses and with evidence of transfer of MRSA between humans and horses 25 and of carriage in horses 26. As would be expected, therapeutic treatment of horses with antimicrobials temporarily increases the prevalence of resistant sentinel Escherichia coli, including multidrug resistance and production of extended spectrum β-lactamases 27, acting as a reminder of the impact of ‘routine’ veterinary therapy on microbial populations. The message is clear that it is time to apply common sense and sound scientific principles to address AMR in equine practice. As a minimum, further surveillance in horses is required, along with universal adoption of responsible use guidelines 28. Irrespective of the scientific uncertainties, AMR is a true One Health issue that is relevant to the equine industry. Whatever the political dimensions of this debate it is essential that the equine veterinary profession and equine industry continue to engage actively with the AMR agenda, promote public and political confidence by demonstrating leadership through responsible use of antimicrobials and monitoring of AMR, and participate in evidence-based practice.

Use of antimicrobials in animals poses a potential risk for public health as it contributes to the selection and spread of antimicrobial resistance. Although knowledge of the negative consequences of extensive antimicrobial use in humans and animals accumulated over the decades, total therapeutic antimicrobial use in farm animals in the Netherlands doubled between 1990 and 2007. A series of facts and events formed a window of opportunity to reduce antimicrobial use in farm animals. The recent discovery of significant reservoirs of antimicrobial-resistant pathogens such as methicillin-resistant Staphylococcus aureus (MRSA) and extended spectrum beta-lactamase-producing bacteria (ESBL) in farm animals, with potential public health implications, combined with an increasing lack of confidence of the public in intensive livestock industries, and discrepancy between the very low antimicrobial use in humans and high use in animals, resulted in intensive collaboration between the government, veterinary professional organizations and important stakeholders within the livestock sector. A combination of compulsory and voluntary actions with clear reduction goals resulted in a 56% reduction in antimicrobial use in farm animals in the Netherlands between 2007 and 2012 and aims at accomplishing a 70% reduction target in 2015. This article describes and analyses the processes and actions behind this transition from an abundant antimicrobial use in farm animals towards a more prudent application of antimicrobials in farm animals in the Netherlands.

Veterinarians play an important role in the reduction of antimicrobial use in farm animals. This study aims to quantify opinions of veterinarians from the Netherlands and Flanders regarding antimicrobial use...

Veterinary antibiotics in the aquatic and terrestrial environment

This paper examines diverse perspectives around the concept of responsibility concerning antibiotic use in animal agriculture. Antibiotic use in agriculture has been identified as a source of antimicrobial resistance, one of the largest public health threats today. In the United States, efforts to curb antibiotic use in farming draws on a diverse range of actors—including farmers, veterinarians, consumers, and public health advocates—and relies on a mix of industry standards and federal guidelines around responsible use. The paper selects a similarly diverse range of people and employs Q methodology to query the points of disagreement and consensus around the practices that constitute responsible antibiotic use in animal agriculture, and who is responsible for antimicrobial resistance. We find a diverse mix of actor types across three discourses, but with clear differences between farmers and public health advocates. We also argue that, in some cases, points of disagreement and agreement are often based on different interpretations of ideas, indicating points of common ground where there might appear to be disagreement, and areas of difference where there appears to be agreement. We argue that these flexible interpretations of some of the key issues around antibiotic use are nevertheless grounded in durable differences in views of what agriculture is and what it should be.

The Antimicrobial Stewardship Guidelines in companion animals are designed to aid practicing veterinarians in choosing appropriate antimicrobial therapy to best serve their patients and minimize the development of antimicrobial resistance and other adverse effects. The Guidelines presented below were developed by an expert task force and provide a recommended framework for judicious antimicrobial use in companion animals.Antimicrobial stewardship, as defined by the American Veterinary Medical Association (AVMA), refers to the actions veterinarians take individually and as a profession to preserve the effectiveness and availability of antimicrobial drugs through conscientious oversight and responsible medical decision-making, while safeguarding animal, public, and environmental health. Stewardship involves: Preventing common diseases through preventive and management strategies.Using evidence-based approaches to make decisions about antimicrobial drugs.Using antimicrobial drugs judiciously and sparingly while evaluating therapeutic outcomes.1The American Animal Hospital Association (AAHA) and the American Association of Feline Practitioners (AAFP) endorse this definition and urge companion animal veterinarians to follow the five core principles of antimicrobial stewardship as defined by the AVMA: commit to stewardship, advocate for a system of care to prevent common diseases, select and use antimicrobial drugs judiciously, evaluate antimicrobial drug use practices, and educate and build expertise.2Veterinarians agree to protect animal and public health when they pledge the Veterinarian's Oath. It is the responsibility of veterinarians to maintain patient health by routine examinations, preventive strategies, and client education. When a medical condition exists, it is important to obtain an accurate clinical diagnosis whenever possible, including determining the likelihood of a bacterial infection that warrants antimicrobial use. Once the decision is made to use antimicrobial therapy, veterinarians should strive to optimize therapeutic efficacy, minimize resistance to antimicrobials, and protect public and animal health.AAHA and the AAFP are committed to the following as described by the AVMA's policy, Judicious Therapeutic Use of Antimicrobials.3Judicious use of antimicrobials in animals requires the oversight of a veterinarian.Judicious use of antimicrobials and extralabel use of antimicrobials should meet all requirements of a valid veterinarian-client-patient relationship (VCPR—see glossary).Preventive strategies, such as appropriate husbandry and hygiene, routine health monitoring, and vaccinations, should be emphasized.Routine preventive healthcare in cats and dogs includes the following: Adherence to the AAFP's guidelines for feline vaccinations and AAHA's guidelines for canine vaccinations.Parasite control, nutritional counseling, and dental health care.Client education and involvement to successfully adopt good preventive health care programs.Appropriate hygiene and husbandry is especially important in multiple pet households.The routine prophylactic use of antimicrobials should never be used as a substitute for good animal health management.The use of antimicrobials to prevent infection (e.g., prophylaxis)4 can only be justified in cases where bacterial infection is likely to occur or where the implications of infection are particularly high (e.g., central nervous system surgery).Recognize risk factors for infections in cats and dogs and prevent or correct them whenever possible. These include, but are not limited to:Urinary catheterizationIntravenous cathetersWoundsEnvironmental factors (i.e., stress, crowding, poor hygiene, transportation, temperature extremes, poor ventilation, and high humidity)Feline leukemia virus, feline immunodeficiency virus infection, or debilitating diseaseImmunosuppressive drugs (e.g., chemotherapeutic agents and glucocorticoid therapy)Endocrine diseases (i.e., diabetic cats are more prone to urinary tract, skin, and mouth infections; dogs with hyperadrenocorticism are more prone to skin and urinary tract infections)Therapeutic alternatives should be considered before, or in conjunction with, antimicrobial therapy.This includes supportive care, such as correction of fluid and electrolyte abnormalities, maintaining acid-base balance, and ensuring adequate nutrition.Surgical intervention may be necessary in some cases, such as abscessation, empyema, or other diseases requiring source control.Consider supportive care, including dietary therapy and probiotics for acute, nonfebrile diarrhea.5,12,13Consider antiseptic preparations and topical (e.g., skin) or locally applied antimicrobials (e.g., oral cavity) as alternatives to systemic antimicrobials.6,7Considerations should be made whether to delay or alter antimicrobial therapy based on patient status.Use delayed prescribing or watchful waiting if a patient's disease might not be caused by a bacterial infection or in certain situations in which patients are expected to clear an infection on their own.Reassess the need for and choice of antimicrobial drugs throughout the course of therapy (antimicrobial "time out").2,8Therapeutic antimicrobial use should be confined to appropriate clinical indications.A definitive diagnosis that indicates antimicrobial therapy is appropriate should be established whenever possible, and empirical use of antimicrobials should be avoided.Practitioners should strive to rule out viral infections, parasitism, mycotoxicosis, nutritional imbalances, neoplasia, and other ailments that will not respond to antimicrobial therapies.Antimicrobial therapy is not indicated in most upper respiratory infections (e.g., feline herpesvirus or calicivirus and canine infectious respiratory disease complex) not suspected to be complicated by secondary bacterial infection.Most cases of pancreatitis in dogs and cats are not associated with bacterial infection.Most cases of feline lower urinary tract disease do not involve bacterial infection, particularly in cats younger than 10 years of age, and in such cases, antimicrobials are not indicated.Systemic antimicrobials are usually not indicated for routine dental prophylaxis or after tooth extractions. In cases of periodontitis, systemic antimicrobials are not a substitute for surgical treatment. In most cases of periapical tooth root abscesses, debridement of infective tissue is sufficient to control infection.9Most cases of acute diarrhea are not due to pathogenic bacterial infections or are self-limiting, so antimicrobials are not indicated, do not hasten time to clinical resolution, and may cause further dysbiosis.10–13Therapeutic antimicrobial use should be applied appropriately in the surgical setting.Administration of antimicrobials should not replace appropriate sterile technique.Surgical antimicrobial prophylaxis is the use of a very brief course of an antimicrobial agent initiated 30–60 minutes before the first incision. Surgical antimicrobial prophylaxis is not usually needed for clean procedures.Sterile technique and proper tissue handling should eliminate the need for prophylactic antibiotics in ovariohysterectomies, orchiectomies, and most other sterile procedures.Ongoing postoperative antimicrobial therapy is rarely required.14Antimicrobials considered important in treating refractory infections in human or veterinary medicine should be used in animals only after careful review and reasonable justification.Consider using other antimicrobials for initial therapy.Drug side effects or interactions should be considered when choosing an appropriate antimicrobial.Ensure any use of antimicrobials considered important in treating refractory infections is supported by the lack of another antimicrobial option, the presence of cytology, culture and susceptibility testing, and a reasonable chance for a cure. Consultation with an expert in infectious disease and antimicrobial therapy should be undertaken when appropriate and available.7,15–19Diagnostic testing, including culture and susceptibility testing, aids in the appropriate selection of antimicrobials.When a urinary tract infection (UTI) (also known as bacterial cystitis) is suspected, urine collected by cystocentesis can help distinguish true bacteriuria from contamination but is not able to distinguish infection from subclinical bacteriuria.Poor urine concentrating ability is a risk factor for bacteriuria. Urine culture coupled with the presence of lower urinary tract signs may be the only way to identify infection in such cases.15The presence of bacteriuria, in the absence of lower urinary tract signs, does not necessarily indicate a UTI and is considered subclinical bacteriuria, which generally does not require antimicrobial treatment.15Antimicrobial susceptibility testing to provide an interpretation of susceptible, intermediate, or resistant to antimicrobial drugs should be done to guide the selection of antimicrobials. Veterinarians should ensure that their reference laboratories use species-specific (i.e., cats and dogs) susceptibility testing breakpoints where available.Performing cytological evaluation of patient samples or body sites is important in advance of and as a complement to culture and antimicrobial susceptibility testing.Because certain antimicrobials are more effective against gram-positive or gram-negative organisms, interim antimicrobial decisions can be based on gram stain and the site of infection.Regimens for therapeutic antimicrobial use should be optimized using current pharmacological information and principles.The antimicrobial chosen should be effective against the organism and be able to penetrate the affected body site in an adequate concentration to eliminate the offending organism.Consider the intrinsic resistance of pathogens to antimicrobials.20,21Consider patient- and site-specific factors that may limit response to antimicrobial therapy (e.g., protected body site and local tissue factors).19Consider patient factors that may influence drug metabolism (e.g., renal or hepatic disease) or concurrent medications that may affect drug levels.For information on dose, route, frequency, and duration of administration, refer to label indications, laboratory standards, and current guidelines from veterinary professional organizations.Risks to patients from antimicrobials should be considered and discussed with owners before use (e.g., enrofloxacin-induced retinotoxicity and aminoglycoside-induced nephrotoxicity).Duration of therapy should be based on scientific and clinical evidence in order to obtain the desired health outcome while minimizing selection for antimicrobial resistance.For specific conditions, refer to appropriate resources and consensus guidelines.7,15,16Antimicrobial therapy must be prescribed in accordance with all local, state, and federal laws (e.g., extralabel usage in the United States).Accurate records of treatment, outcome, and indication for use should be maintained to evaluate therapeutic regimens.Veterinarians should work with animal owners and caretakers to ensure the judicious use of antimicrobials.Administration instructions for antimicrobials must be made clear and labeled correctly (e.g., doxycycline capsules or tablets must be followed by a liquid to avoid esophageal stricture).Clients should be advised to administer medications as directed by their veterinarian, including medication timing and duration of use.As with all medications, proper client instruction in administration techniques is crucial to ensure compliance and safety of the pet and the owner.Clients should be warned of potential adverse reactions and instructed on what to do if any such reactions occur (e.g., stop medication and call your veterinarian for further recommendations).Animal owners should consult with their veterinarian before any antibiotic use, even for antibiotics available without a prescription, to ensure positive outcomes and prevent complications.Minimize environmental contamination with antimicrobials whenever possible.22,23Minimize environmental contamination with antimicrobials by following local, state, and federal guidelines for disposal.24Antibiotic—a chemical substance produced by a microorganism that has the capacity, in dilute solutions, to inhibit the growth of or to kill other microorganisms. Often used interchangeably with "antimicrobial agent."4Antimicrobial—an agent that kills microorganisms or suppresses their multiplication or growth. This includes antibiotics and synthetic agents. Often used interchangeably with "antibiotic."4Antimicrobial resistance—a property of microorganisms that confers the capacity to inactivate or elude antimicrobials or a mechanism that blocks the inhibitory or killing effects of antimicrobials.4Extralabel—actual use or intended use of a drug in a manner that is not in accordance with the approved labeling. This includes, but is not limited to, use in species not listed in the labeling, use for indications (disease or other conditions) not listed in the labeling, use at dosage levels, frequencies, or routes of administration other than those stated in the labeling, and deviation from the labeled withdrawal time based on these different uses.Intrinsic resistance—inherent or innate (not acquired) antimicrobial resistance, which is reflected in all or almost all representatives of a bacterial species.19Minimal inhibitory concentration (MIC)—the lowest concentration of an antimicrobial agent that prevents visible growth of a microorganism in an agar or broth dilution susceptibility test.19Monitoring—includes periodic health surveillance of the population or individual animal examination.Therapeutic—treatment, control, and prevention of bacterial disease.4Antimicrobial prevention of disease (synonym: prophylaxis): Prevention is the administration of an antimicrobial to an individual animal to mitigate the risk of acquiring disease or infection that is anticipated based on history, clinical judgment, or epidemiological knowledge.On a population basis, prevention is the administration of an antimicrobial to a group of animals, none of which have evidence of disease or infection, when transmission of existing undiagnosed infections, or the introduction of pathogens, is anticipated based on history, clinical judgment, or epidemiological knowledge.Antimicrobial control of disease (synonym: metaphylaxis): Control is the administration of an antimicrobial to an individual animal with a subclinical infection to reduce the risk of the infection becoming clinically apparent, spreading to other tissues or organs, or being transmitted to other individuals.On a population basis, control is the use of antimicrobials to reduce the incidence of infectious disease in a group of animals that already has some individuals with evidence of infectious disease or evidence of infection.Antimicrobial treatment of disease:Treatment is the administration of an antimicrobial as a remedy for an individual animal with evidence of infectious disease.On a population basis, treatment is the administration of an antimicrobial to those animals within the group with evidence of infectious disease.Antimicrobial time-out—an active reassessment of an antimicrobial prescription 48–72 hours after first administration to allow medical staff to take into account laboratory culture and susceptibility testing results and the patient's response to therapy and current condition.8Watchful waiting—an approach to patient care in which the veterinarian believes a patient's illness will likely resolve on its own but remains vigilant in case an antibiotic is later needed. The pet owner is provided with instructions on when and why to follow up with the veterinarian and given recommendations for nonantibiotic approaches to improve the patient's comfort.8Veterinarian/Client/Patient Relationship (VCPR)—a VCPR exists when all of the following conditions have been met: The veterinarian has assumed the responsibility for making clinical judgments regarding the health of the animal(s) and the need for medical treatment, and the client has agreed to follow the veterinarian's instructions.The veterinarian has sufficient knowledge of the animal(s) to initiate at least a general or preliminary diagnosis of the medical condition of the animal(s). This means that the veterinarian has recently seen and is personally acquainted with the keeping and care of the animal(s) by virtue of an examination of the animal(s) or by medically appropriate and timely visits to the premises where the animal(s) are kept.The veterinarian is readily available for follow-up evaluation, or has arranged for emergency coverage, in the event of adverse reactions or failure of the treatment regimen.The Task Force has updated the 2014 AAFP/AAHA Basic Guidelines for Judicious Therapeutic Use of Antimicrobials and thanks past contributors for their work.

Occurrence of glycopeptide resistance among Enterococcus faecium isolates from conventional and ecological poultry farms.

BackgroundAntimicrobial resistance is a public health threat. Because antimicrobial consumption in food-producing animals contributes to the problem, policies restricting the inappropriate or unnecessary agricultural use of antimicrobial drugs are important. However, this link between agricultural antibiotic use and antibiotic resistance has remained contested by some, with potentially disruptive effects on efforts to move towards the judicious or prudent use of these drugs.Main textThe goal of this review is to systematically evaluate the types of evidence available for each step in the causal pathway from antimicrobial use on farms to human public health risk, and to evaluate the strength of evidence within a ‘Grades of Recommendations Assessment, Development and Evaluation‘(GRADE) framework. The review clearly demonstrates that there is compelling scientific evidence available to support each step in the causal pathway, from antimicrobial use on farms to a public health burden caused by infections with resistant pathogens. Importantly, the pathogen, antimicrobial drug and treatment regimen, and general setting (e.g., feed type) can have significant impacts on how quickly resistance emerges or spreads, for how long resistance may persist after antimicrobial exposures cease, and what public health impacts may be associated with antimicrobial use on farms. Therefore an exact quantification of the public health burden attributable to antimicrobial drug use in animal agriculture compared to other sources remains challenging.ConclusionsEven though more research is needed to close existing data gaps, obtain a better understanding of how antimicrobial drugs are actually used on farms or feedlots, and quantify the risk associated with antimicrobial use in animal agriculture, these findings reinforce the need to act now and restrict antibiotic use in animal agriculture to those instances necessary to ensure the health and well-being of the animals.

The article analyses the national and international legal framework for the use of antibiotics in organic livestock farming and formulates conclusions and proposals aimed at improving the current agricultural legislation in this area. It is determined that the reform of Ukrainian legislation on veterinary medicine and feed takes into account the main international requirements for regulating the use of antibiotics in animal husbandry, in particular Regulation (EU) 2019/6 of the European Parliament and of the Council of 11.12.2018 on veterinary medicinal products and repealing Directive 2001/82/EC. For the effective implementation of legislative requirements in practice, the author substantiates the need to continue work in the following areas: development of bylaws in the field of antimicrobial use in animal husbandry; collection, accumulation and analysis of information on the volume and types of antibiotics used by agricultural producers; development of improved animal husbandry technologies without the use of antimicrobial agents, taking into account the positive experience of other countries; dissemination of knowledge about such technologies among the subjects of animal husbandry. As a result of the study of the current legislation in the field of organic agricultural production, it was concluded that the legal regulation of the use of antibiotics in organic livestock farming generally meets international requirements, namely such basic documents as Commission Regulation (EC) No. 889/2008 of 5.09.2008 “Detailed rules on organic production, labelling and control to implement Council Regulation (EC) No. 834/2007 on organic production and labelling of organic products” and Council Regulation (EC) No. 834/2007 on organic. To improve the mechanism of control and traceability of the use of antibiotics in the treatment of farm animals in organic livestock, it is proposed to: accelerate the work on the adoption of the Procedure for the Use of Antimicrobial Products in Veterinary Medicine; supplement the Procedure (detailed rules) for organic production and circulation of organic products with provisions on the requirements for documentary evidence of the use of antimicrobial products by operators, and the storage periods for relevant documents.

Antibiotic use in animal agriculture contributes significantly to antibiotic use globally and is a key driver of the rising threat of antibiotic resistance. It is becoming increasingly important to better understand antibiotic use in livestock in low-and-middle income countries where antibiotic use is predicted to increase considerably as a consequence of the growing demand for animal-derived products. Antibiotic crossover-use refers to the practice of using antibiotic formulations licensed for humans in animals and vice versa. This practice has the potential to cause adverse drug reactions and contribute to the development and spread of antibiotic resistance between humans and animals. We performed secondary data analysis of in-depth interview and focus-group discussion transcripts from independent studies investigating antibiotic use in agricultural communities in Uganda, Tanzania and India to understand the practice of antibiotic crossover-use by medicine-providers and livestock-keepers in these settings. Thematic analysis was conducted to explore driving factors of reported antibiotic crossover-use in the three countries. Similarities were found between countries regarding both the accounts of antibiotic crossover-use and its drivers. In all three countries, chickens and goats were treated with human antibiotics, and among the total range of human antibiotics reported, amoxicillin, tetracycline and penicillin were stated as used in animals in all three countries. The key themes identified to be driving crossover-use were: (1) medicine-providers’ and livestock-keepers’ perceptions of the effectiveness and safety of antibiotics, (2) livestock-keepers’ sources of information, (3) differences in availability of human and veterinary services and antibiotics, (4) economic incentives and pressures. Antibiotic crossover-use occurs in low-intensity production agricultural settings in geographically distinct low-and-middle income countries, influenced by a similar set of interconnected contextual drivers. Improving accessibility and affordability of veterinary medicines to both livestock-keepers and medicine-providers is required alongside interventions to address understanding of the differences between human and animal antibiotics, and potential dangers of antibiotic crossover-use in order to reduce the practice. A One Health approach to studying antibiotic use is necessary to understand the implications of antibiotic accessibility and use in one sector upon antibiotic use in other sectors.

The use in animal husbandry of antimicrobials to treat bacterial infections remains unavoidable. However, the use of antimicrobials provokes antimicrobial resistance (AMR), therefore, there is a continuing effort to reduce veterinary antimicrobial use. A potential challenge is the transmission of residues and AMR from treated to untreated animals housed in the same environment. Taking this into consideration, alternative animal keeping practices should be explored. So far, there is little published research aiming to abate, especially the transmission of antimicrobial residues from treated to untreated animals and their environment. In this study, two animal husbandry practices were investigated, exploring the effect of physical separation on the transmission of oxytetracycline residues and the occurrence of antimicrobial resistance. Residue levels were analysed in internal (manure, urine, blood, and saliva) and external (wipes and hair) matrices. Additionally, antimicrobial resistance of Escherichia coli isolated from manure and the environment was assessed. When calves were housed in the same pen during treatment, residues were found not only in the treated animal but also observed in all tested matrices (internal and external) of the untreated pen-mate. When calves were physically separated during treatment to the end of the withdrawal period, no residues were detected in internal matrices of the untreated animals, indicating that transmission can be effectively prevented. Contamination of the pen and the exterior of the animals is also drastically reduced by the separation of animals during treatment and the withdrawal period. AMR results seem to indicate that tetracycline resistance levels return more or less to pre-treatment levels after the withdrawal period. In conclusion, it is recommended to physically separate calves for the duration of both treatment and the withdrawal period, in order to minimise and/or prevent transmission of oxytetracycline residues to untreated animals.

The epidemic of antimicrobial resistant infections continues to challenge, compromising animal care, complicating food animal production and posing zoonotic disease risks. While the overall role of therapeutic antimicrobial use in animals in the development AMR in animal and human pathogens is poorly defined, veterinarians must consider the impacts of antimicrobial use in animal and take steps to optimize antimicrobial use, so as to maximize the health benefits to animals while minimizing the likelihood of antimicrobial resistance and other adverse effects. This consensus statement aims to provide guidance on the therapeutic use of antimicrobials in animals, balancing the need for effective therapy with minimizing development of antimicrobial resistance in bacteria from animals and humans.

American Association of Feline Practitioners basic guidelines of judicious therapeutic use of antimicrobials in cats (approved by the AVMA Executive Board, June 2001)

Antimicrobial use in animal agriculture contributes to antimicrobial resistance in humans, which imposes significant health and economic costs on society. These costs are negative externalities. We review the relevant literature and develop a model to quantify the external costs of antimicrobial use in animal agriculture on antimicrobial resistance in humans. Parameters required for this estimate include: 1) the health and economic burden of antimicrobial resistance in humans, 2) the impact of antimicrobial use in animal agriculture on antimicrobial resistance in animals, 3) the fraction of antimicrobial resistance in humans attributable to animal agriculture, and 4) antimicrobial use in animals. We use a well-documented historic case to estimate an externality cost of about $1500 per kilogram of fluoroquinolones administered in US broiler chicken production. Enhanced data collection, particularly on parameters 3) and 4), would be highly useful to quantify more fully the externalities of antimicrobial use in animal agriculture.

Global resistance to antimicrobials and their sustainable use in agriculture