Antimicrobial prescribing guidelines for sheep

Antimicrobial resistance (AMR) is a growing global threat that presents a serious risk to human and animal health. Resistance to antimicrobials occurs naturally in microorganisms. But it can be amplified by antimicrobial overuse, underuse, or poor management. Hence, the effective stewardship of antimicrobials—through appropriate and judicious manufacture, administering, dispensing, prescribing and disposal—is critical.

Here, in Australia, the veterinary profession and food producing animal industries have a long history of addressing AMR, working diligently to ensure the safe and continued efficacy of antimicrobials. Their previous and ongoing work—a result of partnerships across the animal sector—has resulted in demonstrated low levels of antimicrobial resistant bacteria in food producing animals. It is encouraging that, in the United Kingdom's 2015 O'Neill Review into Antibiotic Resistance, Australia was ranked the fifth lowest for antibiotic use in agriculture among the 29 countries examined. Strict regulation on antimicrobial registration, high levels of biosecurity and extensive farming systems that do not favour bacterial disease also contribute to the low risk of AMR development from animals in Australia.

With the recent release of Australia's National Antimicrobial Resistance Strategy–2020 and Beyond (2020 AMR Strategy), the veterinary profession will continue to play a critical role in how we minimise AMR. The antimicrobial prescribing guidelines for sheep seeks to “ensure that coordinated, evidence based antimicrobial prescribing guidelines and best practice supports are developed and made easily available, and encourage their use by prescribers”.

These practical guidelines for Australian sheep veterinarians are designed to be a useful resource. They have been developed specifically for the Australian sheep industry and contain best-practice information to help clinical veterinarians make appropriate decisions when prescribing antimicrobials.

They encourage veterinarians to first pause and consider the need to use antimicrobials in the situation and whether there are effective non-antimicrobial alternatives. Prevention and control of infections through strict on-farm biosecurity minimises the need to use antimicrobials. Vaccination may also be available to control several important sheep diseases. If antimicrobial use is indicated, practitioners should consider the five rights—right drug, right time, right dose, right duration and right route. Using a lower rating or narrow-spectrum antimicrobial is the preferred approach, and you can also refer to the Australian Antibacterial Importance Ratings to help with these decisions.

I commend the work of all involved in the development of these guidelines and urge every sheep veterinarian to use this advice. In doing so, you'll help safeguard ongoing access to antimicrobials, ensure their long-term efficacy, deliver the best possible veterinary service to the Australian sheep industry, and play your role in the global response to AMR.

Dr Mark Schipp

Australian Chief Veterinary Officer

President of the OIE World Assembly

For much of a 50+ year career as a veterinarian, Ray has been involved in a range of professional activities associated with sheep. This has included research on caseous lymphadenitis and ovine meat inspection standards, international projects, as a rural practitioner or consultant to individual producers, and as an adviser to service or support organisations of the sheep industry.

From teaching and working in both medical and veterinary microbiology, Ray developed a special interest in applying laboratory antimicrobial susceptibility testing to appropriate clinical use.

Appointment to a state reference group developing control of use regulation fostered an ongoing interest in managing risk from administering veterinary chemicals. This extended to undertaking investigations on behalf of and providing advice to a veterinary chemical company supplying products registered for sheep.

Ray has been convenor of continuous professional development for SCGV and its predecessor ASV, as well as presenting at national and international conferences and publishing in refereed scientific journals.

Paul Nilon graduated in veterinary science in 1983 and completed a Masters with the Mackinnon Project in sheep and beef production in 1986. Since then, Paul has worked in rural practice in 3 states, and for the last 15 years as a full time health and production adviser to sheep and beef clients in Tasmania, as well as the occasional gig with sheep and beef R & D corps, research projects with universities and pharmaceutical companies and some training and surveillance with the Tasmanian government.

Paul has been a member of state steering committees for footrot and OJD. He was a member of the Paraboss technical committee and contributes monthly to the Paraboss website. Paul has been trained to represent Wool Producers Australia on the CCEAD in the event of an exotic disease incursion. Paul was the president of the ASV and a committee member.

Paul cites the collegiality of a small, dedicated group of government and private vets and ag scientists as being an essential element to providing animal health and welfare, biosecurity, and production advice to the sheep industries in all states.

Jacqui is Professor of Veterinary Microbiology and Infectious Diseases and Head of School and Dean of the Sydney School of Veterinary Science, at the University of Sydney. She is a registered practicing veterinarian and is passionate about practical research projects and education programs for veterinary professionals, animal breeders, and animal owners. Her main research areas include: (1) Development of diagnostics and treatments for companion animal viral diseases; (2) Q fever; (3) Multidrug resistant (MDR) Staphylococcus species; (4) Infection prevention and control in veterinary practices; (5) Chronic renal disease in domestic and zoo Felids and 6) Factors influencing antimicrobial prescribing behaviour of vets and health professionals. She is a co-founder of the AMR Vet Collective (www.amrvetcollective.com).

Stephen is a consultant veterinary clinical pharmacologist and toxicologist and founder and sole director of Advanced Veterinary Therapeutics–a consulting company that provides advice on appropriate use of veterinary medicines to veterinarians, veterinary organisations (Australian Veterinary Association, World Veterinary Association, World Organisation for Animal Health), state and national government departments and statutory bodies (APVMA, Department of Agriculture, Department of Health, US Environmental Protection Agency), and global organisations (OIE, FAO, Chatham House).

He is a member of the AVA Antimicrobial of Resistance Advisory Group (ARAG), a member of the ASTAG committee on antimicrobial prioritisation; in 2017, he became President of the ANZCVS Chapter of Pharmacology, and is a Stephen is a consultant veterinary clinical pharmacologist and toxicologist and founder and sole director of Advanced Veterinary Therapeutics–a consulting company that provides advice on appropriate use of veterinary medicines to veterinarians, veterinary organisations (Australian Veterinary Association, World Veterinary Association, World Organisation for Animal Health), state and national government departments and statutory bodies (APVMA, Department of Agriculture, Department of Health, US Environmental Protection Agency), and global organisations (OIE, FAO, Chatham House).

He is a member of the AVA Antimicrobial of Resistance Advisory Group (ARAG), and a member of the ASTAG committee on antimicrobial prioritisation; in 2017, he became President of the ANZCVS Chapter of Pharmacology, and is a member the World Veterinary Association Pharmaceutical Stewardship Committee.

He has more than 100 publications on which he is author or editor, including chapters on antimicrobial stewardship, clinical pharmacology, adverse drug reactions, use of antimicrobial agents in livestock, and antimicrobial drug discovery and models of infection.

He has been a teacher and facilitator of courses at the University of Sydney on food safety, public health and antimicrobial resistance since 2003.

He is regularly invited to speak nationally and internationally at a broad range of conferences and symposia, especially on the subjects of antimicrobial use, antimicrobial stewardship, and risk assessment. He gave his first presentation on veterinary antimicrobial resistance and stewardship at the AVA Conference in Perth in 2000 and remains passionate about improving the use and effective life span of antimicrobial agents.

Glenn Browning is Distinguished Professor in Veterinary Microbiology, Director of the Asia-Pacific Centre for Animal Health and Director of Research at the Melbourne Veterinary School at the University of Melbourne. He completed a Bachelor of Veterinary Science with First Class Honours at the University of Sydney in 1983, a postgraduate Diploma of Veterinary Clinical Studies in Large Animal Medicine and Surgery at the University of Sydney in 1984 and a PhD in Veterinary Virology at the University of Melbourne in 1988.

He was a Veterinary Research Officer at the Moredun Research Institute in Edinburgh from 1988 to 1991, investigating viral enteritis in horses, then joined the staff of the Faculty of Veterinary Science at the University of Melbourne, and has been a member of teaching and research staff there since 1991. He teaches in veterinary and agricultural microbiology.

He is a Life Fellow of the Australian Veterinary Association, a Fellow of the Australian Society for Microbiology and Chair of the International Organisation for Mycoplasmology.

He is a co-author of 280 peer reviewed research papers and book chapters, has edited two books on recent progress in understanding the mycoplasmas, and has co-supervised 60 research higher degree students. His research interests include the molecular pathogenesis and epidemiology of bacterial and viral pathogens of animals, the development of novel vaccines and diagnostic assays to assist in control of infectious diseases, and antimicrobial stewardship in veterinary medicine.

Derived from: Page S, Prescott J and Weese S. Veterinary Record 2014;175:207–208. Image courtesy of Trent Hewson, TKOAH.

While the published literature is replete with discussion of misuse and overuse of antimicrobial agents in medical and veterinary situations, there has been no generally accepted guidance on what constitutes appropriate use. To redress this omission, the following principles of appropriate use have been identified and categorised after an analysis of current national and international guidelines for antimicrobial use published in the veterinary and medical literature. Independent corroboration of the validity of these principles has recently been provided by the publication (Monnier et al 2018) of a proposed global definition of responsible antibiotic use that was derived from a systematic literature review and input from a multidisciplinary international stakeholder consensus meeting. Interestingly, 22 elements of responsible use were also selected, with 21 of these 22 elements captured by the separate guideline review summarised below.

Apply appropriate biosecurity, husbandry, hygiene, health monitoring, vaccination, nutrition, housing, and environmental controls. Use Codes of Practice, Quality Assurance Programmes, Herd Health Surveillance

Efficacious, scientific evidence-based alternatives to antimicrobial agents can be an important adjunct to good husbandry practices.

Make clinical diagnosis of bacterial infection with appropriate point of care and laboratory tests, and epidemiological information.

Develop outcome objectives (for example clinical or microbiological cure) and implementation plan (including consideration of therapeutic choices, supportive therapy, host, environment, infectious agent and other factors).

Consider other options first; antimicrobials should not be used to compensate for or mask poor farm or veterinary practices.

Report to appropriate authorities any reasonable suspicion of an adverse reaction to the medicine in either treated animals or farm staff having contact with the medicine, including any unexpected failure to respond to the medication.

Thoroughly investigate every treated case that fails to respond as expected.

Retain an objective and evidence-guided assessment of current practice and implement changes when appropriate to refine and improve infection control and disease management.

Each of the core principles is important but CORE PRINCIPLE 11 Extra-label (off label) Antimicrobial Therapy can benefit from additional attention as veterinarians, with professional responsibility for prescribing and playing a key role in residue minimisation, must consider the tissue residue and withholding period (WHP) and, if necessary, export slaughter interval (ESI) implications of off-label use before selecting this approach to treatment of animals under their care (Reeves 2010; APVMA 2018).

An example of the relationship between the maximum residue limit (MRL) and tissue depletion following administration of a veterinary medicine. In a healthy animal (A), tissue depletion to the MRL often occurs at a time point shorter than the withholding period (WHP) that has been established for the 99/95th percentile of the population. In such an individual animal, if the dose is doubled, tissue depletion (B) should only require one more half-life and would most likely still be within the established WHP. However, if the half-life doubles due to disease or other factors, depletion (C) would now require double the normal WHP and may still result in residues exceeding the MRL (adapted from Riviere and Mason, 2011)

APVMA. Residues and Trade Risk Assessment Manual. Version 1.0 DRAFT. Australian Pesticides and Veterinary Medicines Authority, Kingston, ACT, 2018.

Craigmill AL, Riviere JE, Webb AI. Tabulation of FARAD comparative and veterinary pharmacokinetic data. Wiley-Blackwell, Ames, Iowa, 2006.

Monnier AA, Eisenstein BI, Hulscher ME, Gyssens IC, Drive-AB. WP1 group. Towards a global definition of responsible antibiotic use: results of an international multidisciplinary consensus procedure. J Antimicrob Chemother 2018;73:3-16.

Reeves PT. Drug Residues. In: Cunningham F, Elliott J, Lees P, editors. Comparative and Veterinary Pharmacology. Springer Berlin Heidelberg, Berlin, Heidelberg, 2010:265-290.

Riviere JE, Mason SE. Tissue residues and withdrawal times. In: Riviere JE, editor. Comparative Pharmacokinetics Principles, Techniques, and Applications. 2nd edn. Wiley-Blackwell, Oxford, UK, 2011:413-424.

The following chapters provide additional material on some of the more common and important diseases of sheep. This does not include all conditions listed in Table 3.