Antimicrobial stewardship in equine practice

Antimicrobial stewardship involves the judicious use of antimicrobials balanced against the requirement to treat the presenting clinical condition. The same mandate and principles as discussed in human medicine and other veterinary disciplines are relevant to equine practice. This brief review will focus on available resources for equine practitioners, emerging perspectives on antimicrobial use and stewardship, and opportunities for more effective antimicrobial use in equine practice. There is a need for improved client education, availability of faster and more accurate techniques for identification and sensitivity testing of bacterial pathogens, and the development of novel agents.     

Antimicrobial stewardship in the dairy industry: responding to the threat of antimicrobial resistance

Dairy Australia is the national service body for the Australian dairy industry. Its role is to help farmers adapt to a changing operating environment and achieve a profitable, sustainable dairy industry. Although the use of antibiotics in Australian agriculture is relatively low in global terms, Dairy Australia recognises important drivers for continuous improvement in antimicrobial stewardship (AMS). Dairy Australia’s first strategic priority is to support profitable farms. This priority has driven the development of a range of on‐farm change management programs in the animal health and welfare fields to optimise the unit cost of production and dairy cattle welfare. Dairy Australia’s third strategic priority is to further develop a ‘trusted dairy industry’. Previous and current work under these two strategies position the dairy industry favourably with respect to confronting the challenge of antimicrobial resistance (AMR) and supporting sound AMS with the guiding principle of ‘as little as possible, as much as necessary’. However, given an incomplete but ongoing threat of AMR, more work is needed. Supported by Dairy Australia, the dairy industry has developed an antimicrobial use strategy aligning with the Australian Animal Sector National AMR Plan 2018.     

Antimicrobial labelling in Australia: a threat to antimicrobial stewardship?

Antimicrobial resistance is a public health emergency, placing veterinary antimicrobial use under growing scrutiny. Antimicrobial stewardship, through appropriate use of antimicrobials, is a response to this threat. The need for antimicrobial stewardship in Australian veterinary practices has had limited investigation. A 2016 survey undertaken to investigate antimicrobial usage patterns by Australian veterinarians found that antimicrobial dose rates were varied and often inappropriate. Doses of procaine penicillin in horses and cattle were often low, with 68% and 90% of respondents, respectively, reporting doses that were unlikely to result in plasma concentrations above minimum inhibitory concentrations for common equine and bovine pathogens. Frequency of penicillin administration was also often inappropriate. Gentamicin doses in horses were largely appropriate (89% of dose rates appropriate), but 9% of respondents reported twice daily dosing. Amoxycillin and amoxycillin‐clavulanate were administered at the appropriate doses, or above, to dogs and cats by 54% and 70% of respondents, respectively. Here, we explore the potential reasons for inappropriate antimicrobial dose regimens and report that antimicrobial labels often recommend incorrect dose rates and thus may be contributing to poor prescribing practices. Changes to legislation are needed to ensure that antimicrobial drug labels are regularly updated to reflect the dose needed to effectively and safely treat common veterinary pathogens. This will be especially true if changes in legislation restrict antimicrobial use by veterinarians to the uses and doses specified on the label, thus hampering the current momentum towards improved antimicrobial stewardship.     

Systemic antimicrobial therapy in foals

Antimicrobial agents are commonly used in neonatal foals for the treatment or prevention of sepsis. However, due to concerns about the development of antimicrobial resistance and increasing pressure on veterinarians to rationalise antimicrobial use, we should be trying to reduce the unnecessary use of antimicrobials. This article reviews many of the important considerations when selecting an antimicrobial for use in neonatal foals. Firstly, we consider general differences in neonatal pharmacology and physiology. Secondly, we review common antimicrobial drugs and their indications. Finally, we review antimicrobial stewardship.     

Antibiotic prophylaxis in veterinary cancer chemotherapy: A review and recommendations

Bacterial infection following cancer chemotherapy‐induced neutropenia is a serious cause of morbidity and mortality in human and veterinary patients. Antimicrobial prophylaxis is controversial in the human oncology field, as any decreased incidence in bacterial infections is countered by patient adverse effects and increased antimicrobial resistance. Comprehensive guidelines exist to aid human oncologists in prescribing antimicrobial prophylaxis but similar recommendations are not available in veterinary literature. As the veterinarian's role in antimicrobial stewardship is increasingly emphasized, it is vital that veterinary oncologists implement appropriate antimicrobial use. By considering the available human and veterinary literature we present an overview of current clinical practices and are able to suggest recommendations for prophylactic antimicrobial use in veterinary cancer chemotherapy patients.     

Improving clinical outcomes via responsible antimicrobial use in horses

The growing problem of antimicrobial resistance affects veterinarians on a daily basis. Antimicrobial stewardship and responsible prescribing are essential for a future with effective antimicrobials, as it is unlikely that new antimicrobials will become available for use in horses in the near future. Extended-spectrum β-lactamase (ESBL) producing Enterobacteriaceae, methicillin-resistant Staphylococcus aureus (MRSA) and Salmonella spp. are pathogens of significant concern but there are also other opportunistic pathogens such as Pseudomonas spp., α-haemolytic Streptococcus spp., Enterococcus spp. and Acinetobacter spp. which, due to their high intrinsic resistance, have limited treatment options in adult horses. It is essential that highest priority critically important antimicrobials such as ceftiofur, enrofloxacin, rifampicin and polymyxin B are used prudently in horses and ideally based on culture and antimicrobial susceptibility testing (AST). For example, the use of polymyxin B at a low anti-endotoxic dose rather than at a higher antimicrobial dose in horses for the treatment of systemic inflammatory response syndrome is a potential driver for resistance to colistin (polymyxin E), an antimicrobial used as a last resort in the treatment of multidrug resistant (MDR) Enterobacteriaceae infections in humans. Serum procalcitonin levels are used in humans to distinguish noninfectious inflammatory conditions from inflammation caused by bacteria and other infectious agents and are also used to guide cessation of antimicrobial treatment. Although no such studies have been performed in horses, this or other markers may prove to be helpful in guiding antimicrobial treatment decisions in the future. Optimising sampling techniques and good communication with the microbiology laboratory are essential for generating the accurate culture and AST results that underpin appropriate antimicrobial use. Additionally, there is clearly a need for national and international harmonisation of laboratory methods in order to improve the reliability and consistency of results reported by different laboratories.     

Overview of the use of antimicrobial drugs for the treatment of bacterial infections in horses

The use of antimicrobials in veterinary medicine is under great scrutiny with the emergence of antimicrobial resistance in the human population. Equine veterinarians rely on antimicrobials as an essential tool for the treatment of infections in horses, but there is much criticism of some use, particularly prophylaxis. While the appropriate use of antimicrobials can be justified in equine medicine, the misuse cannot. The definition of appropriate use is complex and involves the indication for therapy, antimicrobial selection, dosing regimen and timing and route of administration, duration of therapy and modification of therapy based on microbial susceptibility and clinical response. The aim of this article is to provide guidance on these factors to assist equine veterinarians in determining what constitutes appropriate antimicrobial use in horses.     

Antimicrobial ratings: the importance of importance

Debate about antimicrobial resistance (AMR) in animals and the impact on humans is often inappropriately focussed on the crude amount of antimicrobials used in animals without deference to issues of ‘intensity of use’, ‘quality of use’ and especially the class of agents being administered. In the latter case, tools for helping to manage how the use of specific antimicrobial agents impact on the risk and consequences of antimicrobial resistance in humans have been available for almost two decades. These consist of antimicrobial ratings systems, which formally define the importance of each individual agent in human health by assigning them to a position on a graduated scale of ‘importance’ comprising up to four categories of risk. Until recently, these published ratings have only had a modest impact on antimicrobial stewardship at the frontline of medical and veterinary practice, although they will undoubtedly have a substantial influence into the future. This article considers the evolution of the available ‘antimicrobial ratings systems’ applicable to Australian and international settings and their pivotal future‐role in the educating of animal managers, policy makers and prescribers. Faithful application of these rating systems at all levels of decision making to do with antimicrobial use is now seen as central to the protection of animals, humans and economies from the scourge of AMR.     

Antimicrobial‐associated diarrhoea in three equine referral practices

Reasons for performing study: Although antimicrobial‐associated diarrhoea (AAD) is the most frequently observed adverse effect of antimicrobial therapy in horses, few multicentred studies on the prevalence of AAD have been performed. Objectives: To determine the prevalence of AAD in horses that developed diarrhoea after antimicrobial treatment for nondiarrhoeic conditions and identify the antimicrobials used. Methods: The 2009 database of 3 referral hospitals was searched to identify nonhospitalised horses (weanling age or older) treated with antimicrobials for nongastrointestinal conditions. Horses with these criteria that presented with diarrhoea during 2009 were included in the study. Additional information, including antimicrobial administered and results of faecal pathogen testing, was gathered on each hospitalised case. Results: Of the 5251 horses treated with antimicrobials for nongastrointestinal signs, 32 were diagnosed with probable AAD, a prevalence of 0.6% (95% confidence interval: 0.43–0.86%). The AAD‐diagnosed horses had an 18.8% (6/32) mortality rate. Horses with AAD had been treated for an average of 4.2 days. The most frequently used antimicrobials in horses with AAD were gentamicin in combination with penicillin (n = 7), enrofloxacin (n = 7) and doxycycline (n = 4). Clostridium difficile was identified in faecal samples from 4 horses, 2 of which died and Salmonella from 3 horses. Conclusions: Results indicated that the prevalence of AAD is low. Any antimicrobial class commonly used in equine practice is a potential cause of equine AAD. Other risk factors, such as opportunistic enteropathogens, may play a part in the development of diarrhoea secondary to antimicrobial usage. Potential relevance: Although the risk of equine AAD is low, this sequela of antimicrobial treatment is possible especially when opportunistic enteropathogens or other risk factors are present. Because drugs from any antimicrobial class can be potentially involved in AAD, clinicians have additional incentive to ensure the judicious use of antimicrobial agents.     

Antimicrobic and anthelmintic resistance.

Antimicrobial and anthelmintic resistance are growing issues for the equine practitioner. The development of antimicrobial or anthelmintic resistance is a source of significant concern because of increased frequency of treatment failures and increased treatment costs. In addition, antimicrobial resistance may have important consequences for public health. Only through judicious use can the efficacy of antimicrobials and anthelmintics be prolonged. This article discusses the development of resistance and suggestions for control.     

International trends impacting antimicrobial stewardship in animal health

The Tripartite collaboration (World Health Organization, the Food and Agriculture Organisation of the United Nations, and the World Organisation for Animal Health) produced two documents for consultation with Member Countries in 2017 ‐ Monitoring and Evaluation of the Global Action Plan on Antimicrobial Resistance: Proposed approach and the Global Framework for Development & Stewardship to Combat Antimicrobial Resistance: Draft Roadmap. These documents intend to support a strategic whole‐of‐system approach towards the World Health Organization's Global Action Plan on Antimicrobial Resistance. This paper outlines the recent thinking in antimicrobial stewardship being developed by the major international organisations involved with mitigating global antimicrobial resistance. The directions being set in key frameworks will need to be considered by Australian stakeholders as their own antimicrobial stewardship approaches and activities are formulated.     

Susceptibility pattern of bacterial isolates in equine ulcerative keratitis: Implications for empirical treatment at a university teaching hospital in Sydney

Corneal ulceration is a common ophthalmic condition in horses. It is frequently caused by trauma to the corneal surface, followed by secondary infection by commensal or pathogenic organisms including Streptococcus equi subspecies zooepidemicus, Pseudomonas aeruginosa and Staphylococcus spp. Emerging antimicrobial resistance amongst these organisms has raised the need for appropriate antimicrobial therapy selection, to optimise treatment efficacy while minimising further antimicrobial resistance. Medical records of 38 horses presented at the University Veterinary Teaching Hospital Camden for ulcerative keratitis between 2010 and 2020 were reviewed to identify those with positive bacterial cultures and antimicrobial susceptibility profiles (13/38). Common susceptibility patterns were identified and used to guide the empirical treatment of equine bacterial corneal ulcers. Pseudomonas spp. (64.3%), Streptococcus equi subspecies zooepidemicus (14.3%) and Actinobacillus spp. (14.3%) were most commonly identified. Susceptibility to amikacin, gentamicin and ciprofloxacin was observed in 100%, 66.7% and 85.7% Pseudomonas spp. isolates respectively. Resistance to polymyxin B and neomycin occurred in 85.7% and 71.4% of Pseudomonas spp., respectively. All Streptococcus equi subspecies zooepidemicus organisms in this study were susceptible to ceftiofur, cephalexin, penicillin and ampicillin, while they were all resistant to gentamicin, neomycin, enrofloxacin and marbofloxacin. Predominating in this study, Pseudomonas spp. maintained overall aminoglycoside susceptibility despite some emerging resistance, and good fluoroquinolone susceptibility. High resistance to Polymyxin B could have arisen from its common use as first-line therapy for bacterial corneal ulcers. Although further research is required, these new findings about predominant bacteria in equine corneal ulceration in the Camden region and their antimicrobial susceptibility patterns can be used to guide the empirical treatment of bacterial corneal ulcers in horses.     

Responsible antimicrobial use in critically ill adult horses

Due to increasing antimicrobial resistance, pressure on veterinarians is mounting to adhere to responsible use of antimicrobial drugs. Antimicrobials are frequently included in the treatment of systemically ill horses due to the strong likelihood of an infection and the innate difficulties in differentiating systemic inflammation secondary to noninfectious from infectious causes. In light of increasing antimicrobial drug resistance and the potential negative impact of antimicrobials on equine patients, every attempt should be made to identify noninfectious disease, choose first-line antimicrobials and discontinue treatment as soon as possible. In most cases, a short duration of antimicrobial therapy ranging from a single dose (e.g. preoperatively) to 24–72 h might be sufficient with long-term treatment being rarely required. This article aims to provide practical guidelines for antimicrobial drug usage in critically ill adult horses by describing ancillary diagnostic aids that can help establishing whether or not an infection is present, discussing commonly encountered pathogens and their typical antimicrobial drug sensitivity patterns, and providing some guidance how to safely shorten the duration of antimicrobial therapy.     

Antibacterial drug resistance and equine practice

The equine practitioner is in a position to make day‐to‐day decisions regarding antimicrobial drug (AMD) use for their patients as well as to educate their clients regarding judicious use. General guidelines regarding judicious use of AMDs in equine patients have been developed by the American Association of Equine Practitioners. Detailed guidelines for AMD use in specific equine diseases supported by clinical trials and results of surveillance studies focused on resistance among equine bacterial pathogens are lacking. Studies that could lead to detailed and justifiable use recommendations would allow the equine practitioner to make more informed decisions regarding when to use AMDs, which drugs should be used and how they should be used (e.g. dose, route and duration).     

Evolution of equine infection control programs.

The science of control of infectious diseases in hospitals was born in 1847 when Semmelweis, a physician, ordered his medical students to scrub their hands in chlorinated lime water between patients and demonstrated that this simple procedure resulted ina dramatic decline in patient morbidity and mortality. In the late nineteenth century came huge breakthroughs in the understanding that microorganisms cause many disorders, and methods to eliminate and control these microorganisms were attempted. By 1910, sterile instruments, gowns, masks, and gloves had become standard for surgical procedures in large university human hospitals, and isolation of human and veterinary patients with contagious diseases became standard. With the advent of vaccines, many epidemic viral diseases could be controlled, and antimicrobial drugs allowed many previously devastating bacterial diseases to be treated effectively. Before long, however, bacterial resistance became an important issue and remains so today, particularly for Salmonella and Staphylococcus aureus in horses. Vaccination has decreased the number of animals susceptible to equine influenza and equine herpesvirus 1, yet these contagious diseases still pose a serious issue in large equine veterinary hospitals. The development of equine isolation facilities and improved methods of barn cleaning; mandatory application of procedures, such as handwashing or use of disinfectant hand wipes, to prevent the spread of infectious diseases; and monitoring of antimicrobial resistance and use of restricted antimicrobial drugs were driven by recognition and necessity and have given rise to current equine infection control programs.     

Antimicrobial use in food and companion animals

The vast literature on antimicrobial drug use in animals has expanded considerably recently as the antimicrobial resistance (AMR) crisis in human medicine leads to questions about all usage of antimicrobial drugs, including long-term usage in intensively managed food animals for growth promotion and disease prevention. Attention is also increasingly focusing on antimicrobial use and on bacterial resistance in companion animals, which are in intimate contact with the human population. They may share resistant bacteria with their owners, amplify resistant bacteria acquired from their owners, and act as a reservoir for human infection. Considerable effort is being made to describe the basis of AMR in bacterial pathogens of animals. Documentation of many aspects of use of antimicrobials in animals is, however, generally less developed and only a few countries can describe quantities of drugs used in animals to kg levels annually. In recent years, many national veterinary associations have produced 'prudent use guidelines' to try to improve antimicrobial drug use and decrease resistance, but the impact of guidelines is unknown. Within the evolving global movement for 'antimicrobial stewardship', there is considerable scope to improve many aspects of antimicrobial use in animals, including infection control and reduction of use, with a view to reducing resistance and its spread, and to preserving antimicrobial drugs for the future.     

Infections caused by multidrug-resistant bacteria in an equine hospital (2012–2015)

Multidrug-resistant (MDR) bacteria are an emerging threat in human and veterinary medicine. There are few reports about infections caused by MDR isolates in horses. The aim of this study was to provide an overview of infections caused by MDR bacteria at the Equine Hospital Zurich between 2012 and 2015. Medical records were searched for horses with confirmed MDR bacterial infection. Multidrug resistance was defined according to human guidelines specific for each pathogen. MDR isolates were most commonly isolated from post-procedural infections (53/110, 48%), followed by musculoskeletal (16/110, 15%) and soft tissue infections (16/110, 15%). Escherichia coli (32/158, 20%) and Staphylococcus aureus (25/158, 16%) were the most common isolates. High resistance rates precluded therapy with commonly used antimicrobial drugs. The overall mortality rate was 20% (22/108) but depended on the localisation of the infection. Antimicrobial treatment prior to development of infection was reported for 89% (91/102) of horses. This study showed that MDR pathogens, mainly MDR E. coli and MRSA, cause a considerable number of infections in horses. A wide range of infections was seen, however, nosocomial infections predominated. These cases are typically hospitalised, pretreated with antibiotics, and suffering from comorbidities putting them at high-risk for acquiring infections caused by MDR isolates. The mortality of such infections was generally low but depended on site of infection.