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Background: Minimizing harm from antimicrobials requires use of the narrowest spectrum drug, at an effective dose for the minimum effective duration. Many prescribers are not currently following these guidelines. To address suboptimal antimicrobial use, the underlying reasons must be understood., Objectives: To identify factors influencing choices of antimicrobial drug, dose, and duration for companion animals., Subjects: Twenty-two veterinarians treating companion animals in Australia. Diversity of participants was deliberately sought., Methods: Semistructured interviews were conducted online. Two case studies were discussed, and then a range of broader questions was posed. Transcripts were analyzed thematically, using an inductive approach., Results: Few participants chose guideline-concordant management for the case studies. Prescribing choices were influenced by a complex array of factors associated with the clinical case, pet owner, drug, veterinarian, veterinary colleagues, and external factors. Key factors driving broad-spectrum antimicrobial use included a sense of safety, habit, ease of administering the drug (especially in cats), pharmaceutical marketing, and the self-perpetuating dispensary cycle. Many participants were concerned about antimicrobial resistance, but insufficiently informed about how to minimize this risk. Several participants believed that longer duration of treatment and ensuring patients finish a predetermined course would decrease the risk of antimicrobial resistance and improve clinical outcomes., Conclusions and Clinical Importance: Veterinarians are engaged with the concept of antimicrobial stewardship, but face numerous practical barriers and require more information. In particular, improved education is needed on enhancing patient safety by minimizing both spectrum of activity and duration of treatment, and dispelling myths about "finishing the course.", (© 2024 The Author(s). Journal of Veterinary Internal Medicine published by Wiley Periodicals LLC on behalf of American College of Veterinary Internal Medicine.)

The European Society for Clinical Microbiology and Infectious Diseases (ESCMID) developed consensus-based generic competencies in antimicrobial prescribing and stewardship. These may be useful in structuring and evaluating antimicrobial prescribing education to veterinary students, but their applicability has not been evaluated. We aimed to evaluate whether the ESCMID competencies are currently taught and how relevant they are to veterinary prescribing in veterinary schools globally. A multi-center, cross-sectional survey was performed by administering an online questionnaire to academics teaching antimicrobial prescribing to veterinary students. Targeted recruitment was undertaken to ensure the representation of diverse geographical locations. Responses (48) were received from veterinary schools in Europe (26), North America (7), Asia (6), Australia (3), Central and South America (3), and Africa (3). Of the 37 ESCMID prescribing competencies, only 6 were considered only "slightly" or "not at all" relevant by more than 10% of respondents. Of the 37 competencies, 25 of the competencies were taught in more than 90% of schools and another 6 were taught in 80%-89% of schools. Time spent teaching was "too little" or "far too little" for five competencies according to more than 50% of the respondents. Additional competencies to address extra-label drug use; the use of compounded antimicrobials; the use of antimicrobials for metaphylaxis, prophylaxis, and growth promotion; and the importance rating of antimicrobials were suggested. The ESCMID antimicrobial prescribing competencies had broad relevance and were widely covered in the veterinary curriculum globally.

In Australia, antimicrobials are given an importance rating by the Australian Strategic and Technical Advisory Group on antimicrobial resistance. High importance antimicrobials are those essential for the treatment or prevention of infections in humans, where there are few or no treatment alternatives. In this study we consulted with experts from across human and animal health using the Delphi consensus-building process to establish the circumstances under which antimicrobials with high importance to human health could be used in animals in Australia. We used three rounds of online surveys. Group responses were provided to participants in each subsequent round to facilitate convergence of opinion. Consensus was defined as 80 % or more of respondents selecting the same option for a question. By the end of the third round, consensus was achieved on eight items. This included the use of high importance antimicrobials being appropriate if culture and sensitivity testing indicated the organism was resistant to low- and medium-rated antimicrobials that could be used to treat the case. If any high-importance antimicrobials are prescribed for animals there was also agreement that a clear indication for this use and justification for antimicrobial choice must be recorded in the medical history, along with the dose rate, route of administration, the duration and the time point for review of the condition and associated antimicrobial therapy. Appropriateness of use of high importance antimicrobials in critically ill animals where culture and sensitivity results are not available is still undefined. Further work is also required to establish which particular organisation should be notified of the use of high importance antimicrobials not registered for use in animals. The Delphi process was valuable in facilitating consensus amongst international experts from a broad range of health backgrounds and experience., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors. Published by Elsevier B.V.)

Hendra virus (HeV) is lethal to horses and a zoonotic threat to humans in Australia, causing severe neurological and/or respiratory disease with high mortality. An equine vaccine has been available since 2012. Foals acquire antibodies from their dams by ingesting colostrum after parturition, therefore it is assumed that foals of mares vaccinated against HeV will have passive HeV antibodies circulating during the first several months of life until they are actively vaccinated. However, no studies have yet examined passive or active immunity against HeV in foals. Here, we investigated anti-HeV antibody levels in vaccinated mares and their foals. Testing for HeV neutralising antibodies is cumbersome due to the requirement for Biosafety level 4 (BSL-4) containment to conduct virus neutralisation tests (VNT). For this study, a subset of samples was tested for HeV G-specific antibodies by both an authentic VNT with infectious HeV and a microsphere-based immunoassay (MIA), revealing a strong correlation. An indicative neutralising level was then applied to the results of a larger sample set tested using the MIA. Mares had high levels of HeV-specific neutralising antibodies at the time of parturition. Foals acquired high levels of maternal antibodies which then waned to below predictive protective levels in most foals by 6 months old when vaccination commenced. Foals showed a suboptimal response to vaccination, suggesting maternal antibodies may interfere with active vaccination. The correlation analysis between the authentic HeV VNT and HeV MIA will enable further high throughput serological studies to inform optimal vaccination protocols for both broodmares and foals., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Antimicrobial stewardship programmes (ASPs) are critically important for improving the appropriate use of antimicrobial agents in veterinary practice., Methods: One of three ASPs was implemented in 135 Australian general veterinary practices in 2018-2020. The ASP interventions and the perceived impact they had on antimicrobial prescribing were assessed by the veterinarians working in these veterinary practices. An online survey was distributed to all 520 veterinarians working in the trial practices and 267 responses were analysed., Results: Most veterinarians (174/267, 65%) thought they had an ASP at their clinic and most respondents who said that they were aware that they had an ASP at their clinic indicated that they had changed the way they prescribed antimicrobials because of the trial (125/170, 74%). Antimicrobial prescribing guidelines, the traffic light system for indicating antimicrobial importance, delayed prescribing and antimicrobial stewardship champions were reported to have had the biggest impact., Limitations: All practices in the trial belong to a single corporate group, which may impact the external validity of these results when applied to general small animal practice., Conclusion: Antimicrobial stewardship has a positive impact on antimicrobial prescribing in veterinary medicine and future interventions should focus on the implementation of the effective interventions identified in this study., (© 2023 The Authors. Veterinary Record published by John Wiley & Sons Ltd on behalf of British Veterinary Association.)

Veterinarians sometimes prescribe antimicrobials even when they know or suspect that they are unnecessary. The drivers of this behaviour must be understood to design effective antimicrobial stewardship interventions. Semi-structured interviews were conducted with 22 veterinarians who treated companion animals in Australia. The Theory of Planned Behaviour was used to organise interview themes, focusing on a decision to withhold antimicrobial therapy in the absence of a clear indication. Many background factors influenced antimicrobial-withholding decisions, including the veterinarian's communication skills, general attitudes towards antimicrobial resistance (AMR), habits and energy levels. Client awareness of AMR and the veterinarian-client relationship were also important. Beliefs about the consequences of withholding antimicrobials (behavioural beliefs) were dominated by fears of the animal's condition deteriorating and of failing to meet client expectations. These fears, weighed against the seemingly distant consequences of AMR, were major barriers to withholding antimicrobials. Normative beliefs were primarily focused on the expected approval (or disapproval) of the client and of other veterinarians. Control beliefs about the difficulty of withholding antimicrobials centred around client factors, most importantly, their capacity to adequately monitor their animal, to pay for further investigations, or to undertake non-antimicrobial management, such as wound care, at home. The use of antimicrobials by companion animal veterinarians in the absence of a clear indication is often powerfully driven by behavioural beliefs, chiefly, fears of clinical deterioration and of failing to meet client expectations.

The timely implementation of antimicrobial stewardship interventions could delay or prevent the development of higher levels of antimicrobial resistance in the future. In food-producing animals in Australia, high-importance antimicrobials, as rated by the Australian Strategic and Technical Advisory Group (ASTAG), include virginiamycin and third-generation cephalosporins (in individual pigs or cattle). The use of high-importance antimicrobials in companion animals is more widespread and less regulated. There is no national antimicrobial use surveillance system for animals in Australia. Consequently, there is a gap in the knowledge about reasonable use across all sectors of veterinary practice. This study explored attitudes towards the use in veterinary medicine of antimicrobials with high importance to human health, and determined levels of agreement about the introduction of restrictions or other conditions on this use. An online survey was distributed via social media and email from June to December 2020 to veterinarians working in Australia. Of the 278 respondents working in clinical practice, 49% had heard of the ASTAG rating system, and 22% used a traffic light system for antimicrobial importance in their practice. Overall, 61% of participants disagreed that veterinarians should be able to prescribe high-importance antimicrobials without restrictions. If there were to be restrictions, there was most agreement amongst all respondents for only restricting high-importance antimicrobials (73%). There is a need for education, guidance, and practical support for veterinarians for prescribing high-importance antimicrobials alongside any restrictions.

Background: Treatment for adults with acute lymphoblastic leukaemia requires improvement. UKALL14 was a UK National Cancer Research Institute Adult ALL group study that aimed to determine the benefit of adding the anti-CD20 monoclonal antibody, rituximab, to the therapy of adults with de novo B-precursor acute lymphoblastic leukaemia., Methods: This was an investigator-initiated, phase 3, randomised controlled trial done in all UK National Health Service Centres treating patients with acute lymphoblastic leukaemia (65 centres). Patients were aged 25-65 years with de-novo BCR-ABL1-negative acute lymphoblastic leukaemia. Patients with de-novo BCR-ABL1-positive acute lymphoblastic leukaemia were eligible if they were aged 19-65 years. Participants were randomly assigned (1:1) to standard-of-care induction therapy or standard-of-care induction therapy plus four doses of intravenous rituximab (375 mg/m 2 on days 3, 10, 17, and 24). Randomisation used minimisation and was stratified by sex, age, and white blood cell count. No masking was used for patients, clinicians, or staff (including the trial statistician), although the central laboratory analysing minimal residual disease and CD20 was masked to treatment allocation. The primary endpoint was event-free survival in the intention-to-treat population. Safety was assessed in all participants who started trial treatment. This study is registered with ClincialTrials.gov, NCT01085617., Findings: Between April 19, 2012, and July 10, 2017, 586 patients were randomly assigned to standard of care (n=292) or standard of care plus rituximab (n=294). Nine patients were excluded from the final analysis due to misdiagnosis (standard of care n=4, standard of care plus rituximab n=5). In the standard-of-care group, median age was 45 years (IQR 22-65), 159 (55%) of 292 participants were male, 128 (44%) were female, one (<1%) was intersex, and 143 (59%) of 244 participants had high-risk cytogenetics. In the standard-of-care plus rituximab group, median age was 46 years (IQR 23-65), 159 (55%) of 294 participants were male, 130 (45%) were female, and 140 (60%) of 235 participants had high-risk cytogenetics. After a median follow-up of 53·7 months (IQR 40·3-70·4), 3-year event-free survival was 43·7% (95% CI 37·8-49·5) for standard of care versus 51·4% (45·4-57·1) for standard of care plus rituximab (hazard ratio [HR] 0·85 [95% CI 0·69-1·06]; p=0·14). The most common adverse events were infections and cytopenias, with no difference between the groups in the rates of adverse events. There were 11 (4%) fatal (grade 5) events in induction phases 1 and 2 in the standard-of-care group and 13 (5%) events in the standard-of-care plus rituximab group). 3-year non-relapse mortality was 23·7% (95% CI 19·0-29·4) in the standard-of-care group versus 20·6% (16·2-25·9) in the standard-of-care plus rituximab group (HR 0·88 [95% CI 0·62-1·26]; p=0·49)., Interpretation: Standard of care plus four doses of rituximab did not significantly improve event-free survival over standard of care. Rituximab is beneficial in acute lymphoblastic leukaemia but four doses during induction is likely to be insufficient., Funding: Cancer Research UK and Blood Cancer UK., Competing Interests: Declaration of interests AKF received institutional peer-reviewed grant funding from Cancer Research UK, the Medical Research Council, and Servier; received consulting fees from Amgen; has a leadership/fiduciary role for the British Society of Haematology (unpaid); and is on a data safety and monitoring board for Novartis. AAK has received honoraria from Kite and Gilead; has received institutional peer-reviewed grant funding from Millennium pharmaceutics, Bristol Myers Squibb, Amgen, Celgene, Merck Sharp and Dohme, Janssen-Cilag, Pfizer, and Cancer Research UK; and is on a data safety and monitoring board or advisory committee for the University of Birmingham. AKM has received honoraria form Amgen, Roche, Abbvie, and Celgene; has received institutional peer-reviewed grant funding from Janssen and AstraZeneca; has received meeting support from Roche, Celgene, and Abbvie; and is on a data safety and monitoring board or advisory committee for Novartis. AVM has received institutional peer-reviewed grant funding from Cancer Research UK, Blood Cancer UK, the EU Innovative Medicines Initiative, and North East Children's Cancer Fund; has a leadership/fiduciary role for the ALLTogther Consortium Board and the Genetics Committee and Science Committee (unpaid); and has received honoraria from Amgen. AZC has received honoraria from Pfizer, Amgen, and Hartley Taylor; and is on a data safety and monitoring board or advisory committee for Pfizer. BB has received institutional peer-reviewed grant funding from Novartis/Haematology Society of Australia and New Zealand (New Investigator Scholarship). CJR has received honoraria from Kite; is on a data safety and monitoring board or advisory committee for Incyte, Gilead, and Pfizer; and has a leadership/fiduciary role as the National Cancer Research Institute Adult ALL Group Chair (unpaid). DIM has received consulting fees from Amgen, Pfizer, Kite, and Novartis; and honoraria from Amgen, Pfizer, and Kite. DY has received meetings support from Amgen, Servier, and Jazz; and is on a data safety and monitoring board or advisory committee for the University of Birmingham, Gilead, and Pfizer. KEB has received research grant support from Blood Cancer UK. LC-H has received institutional peer-reviewed grant funding from Millennium pharmaceutics, Bristol Myers Squibb, Amgen, Celgene., Merck Sharp and Dohme, Janssen-Cilag, Pfizer, and Cancer Research UK. MC has received institutional peer-reviewed grant funding from Cure Leukaemia, Blood Cancer UK, Cyclacel, and Incyte; has received consulting fees from Pfizer, Novartis, and Jazz; has received payment or honoraria from Pfizer, Novartis, Jazz, and Astellias; and has received meeting support from Novartis. PS has received institutional peer-reviewed grant funding from Cancer Research UK, Blood Cancer UK, and Servier. RK has received honoraria from Amgen and Pfizer; and is on a data safety and monitoring board or advisory committee for Amgen. TFM has received honoraria from Amgen, Pfizer, Kite, Gilead, Janssen, Roche, Servier, Novartis, and Celgene; has received institutional peer-reviewed grant funding from Janssen and AstraZeneca; and has received meeting support from Novartis, Amgen, Pfizer, Kite, Gilead, Celgene, Daiichi Sankyo, and Atara. All other authors declare no competing interests., (Copyright © 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Background: Antimicrobial stewardship programmes (ASPs) have been widely implemented in medical practice to improve antimicrobial prescribing and reduce selection for multidrug-resistant pathogens., Objectives: To implement different antimicrobial stewardship intervention packages in 135 veterinary practices and assess their impact on antimicrobial prescribing., Methods: In October 2018, general veterinary clinics were assigned to one of three levels of ASP, education only (CON), intermediate (AMS1) or intensive (AMS2). De-identified prescribing data (1 October 2016 to 31 October 2020), sourced from VetCompass Australia, were analysed and a Poisson regression model fitted to identify the effect of the interventions on the incidence rates of antimicrobial prescribing., Results: The overall incidence rate (IR) of antimicrobial prescribing for dogs and cats prior to the intervention was 3.7/100 consultations, which declined by 36% (2.4/100) in the implementation period, and by 50% (1.9/100) during the post-implementation period. Compared with CON, in AMS2 there was a 4% and 6% reduction in the overall IR of antimicrobial prescribing, and a 24% and 24% reduction in IR of high importance antimicrobial prescribing, attributable to the intervention in the implementation and post-implementation periods, respectively. A greater mean difference in the IR of antimicrobial prescribing was seen in high-prescribing clinics., Conclusions: These AMS interventions had a positive impact in a large group of general veterinary practices, resulting in a decline in overall antimicrobial use and a shift towards use of antimicrobials rated as low importance, with the greatest impact in high-prescribing clinics., (© The Author(s) 2022. Published by Oxford University Press on behalf of British Society for Antimicrobial Chemotherapy.)

Antimicrobial stewardship (AMS) in Australia is supported by a number of factors, including enabling national policies, sectoral clinical governance frameworks and surveillance programmes, clinician-led educational initiatives and health services research. A One Health research programme undertaken by the National Centre for Antimicrobial Stewardship (NCAS) in Australia has combined antimicrobial prescribing surveillance with qualitative research focused on developing antimicrobial use-related situational analyses and scoping AMS implementation options across healthcare settings, including metropolitan hospitals, regional and rural hospitals, aged care homes, general practice clinics and companion animal and agricultural veterinary practices. Qualitative research involving clinicians across these diverse settings in Australia has contributed to improved understanding of contextual factors that influence antimicrobial prescribing, and barriers and facilitators of AMS implementation. This body of research has been underpinned by a commitment to supplementing 'big data' on antimicrobial prescribing practices, where available, with knowledge of the sociocultural, technical, environmental and other factors that shape prescribing behaviours. NCAS provided a unique opportunity for exchange and cross-pollination across the human and animal health programme domains. It has facilitated synergistic approaches to AMS research and education, and implementation of resources and stewardship activities. The NCAS programme aimed to synergistically combine quantitative and qualitative approaches to AMS research. In this article, we describe the qualitative findings of the first 5 years., (© The Author(s) 2021. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy.)

Background: The human and domestic animal faecal microbiota can carry various antimicrobial resistance genes (ARGs), especially if they have been exposed to antimicrobials. However, little is known about the ARG profile of the faecal microbiota of healthy foals. A high-throughput qPCR array was used to detect ARGs in the faecal microbiota of healthy foals., Objectives: To characterise the faecal microbiota and ARG profiles in healthy Australian foals aged less than 1 month., Study Design: Observational study., Methods: The faecal microbiota and ARG profiles of 37 Thoroughbred foals with no known gastrointestinal disease or antimicrobial treatment were determined using 16S rRNA gene sequencing and a high-throughput ARG qPCR array. Each foal was sampled on one occasion., Results: Firmicutes and Bacteroidetes were dominant in the faecal microbiota. Foals aged 1-2 weeks had significantly lower microbiota richness than older foals. Tetracycline resistance genes were the most common ARGs in the majority of foals, regardless of age. ARGs of high clinical concern were rarely detected in the faeces. The presence of ARGs was associated with the presence of class I integron genes., Main Limitations: Samples were collected for a case-control study so foals were not sampled longitudinally, and thus the development of the microbiota as individual foals aged could not be proven. The history of antimicrobial treatment of the dams was not collected and may have affected the microbiota of the foals., Conclusion: The ARGs in foal faeces varied concomitantly with age-related microbiota shifts. The high abundance of tetracycline resistance genes was likely due to the dominance of Bacteroides spp., (© 2020 The Authors. Equine Veterinary Journal published by John Wiley & Sons Ltd on behalf of EVJ Ltd.)

Background: Cefovecin is a long-acting third-generation cephalosporin commonly used in veterinary medicine. Third-generation cephalosporins are critically important antimicrobials that should only be used after culture and susceptibility testing. The authors describe the common indications for cefovecin use in dogs and cats, and the frequency of culture and susceptibility testing., Materials and Methods: A cross-sectional study was performed using clinical records extracted from VetCompass Australia. A previously described method was used to identify records containing cefovecin. The reason for cefovecin use was annotated in situ in each consultation text., Results: Over a six-month period (February and September 2018), 5180 (0.4 per cent) consultations involved cefovecin administration, of which 151 were excluded. Cats were administered cefovecin more frequently than dogs (1.9 per cent of cat consultations and 0.1 per cent of dog consultations). The most common reasons for cefovecin administration to cats were cat fight injuries and abscesses (28 per cent) and dermatitis (13 per cent). For dogs, the most common reasons for cefovecin administration were surgical prophylaxis (24 per cent) and dermatitis (19 per cent). Culture and susceptibility testing were reported in 16 cases (0.3 per cent)., Conclusion: Cefovecin is used in many scenarios in dogs and cats where antimicrobials may be either not indicated or where an antimicrobial of lower importance to human health is recommended., Competing Interests: Competing interests: None declared., (© British Veterinary Association 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

Chronic lung diseases (CLDs), such as chronic obstructive pulmonary disease, interstitial lung disease, and lung cancer, are among the leading causes of morbidity globally and impose major health and financial burdens on patients and society. Effective treatments are scarce, and relevant human model systems to effectively study CLD pathomechanisms and thus discover and validate potential new targets and therapies are needed. Precision-cut lung slices (PCLS) from healthy and diseased human tissue represent one promising tool that can closely recapitulate the complexity of the lung's native environment, and recently, improved methodologies and accessibility to human tissue have led to an increased use of PCLS in CLD research. Here, we discuss approaches that use human PCLS to advance our understanding of CLD development, as well as drug discovery and validation for CLDs. PCLS enable investigators to study complex interactions among different cell types and the extracellular matrix in the native three-dimensional architecture of the lung. PCLS further allow for high-resolution (live) imaging of cellular functions in several dimensions. Importantly, PCLS can be derived from diseased lung tissue upon lung surgery or transplantation, thus allowing the study of CLDs in living human tissue. Moreover, CLDs can be modeled in PCLS derived from normal lung tissue to mimic the onset and progression of CLDs, complementing studies in end-stage diseased tissue. Altogether, PCLS are emerging as a remarkable tool to further bridge the gap between target identification and translation into clinical studies, and thus open novel avenues for future precision medicine approaches.

Maintaining the three-dimensional architecture and cellular complexity of lung tissue ex vivo can enable elucidation of the cellular and molecular pathways underlying chronic pulmonary diseases. Precision-cut lung slices (PCLS) are one human-lung model with the potential to support critical mechanistic studies and early drug discovery. However, many studies report short culture times of 7-10 days. Here, we systematically evaluated poly(ethylene glycol)-based hydrogel platforms for the encapsulation of PCLS. We demonstrated the ability to support ex vivo culture of embedded PCLS for at least 21 days compared with control PCLS floating in media. These customized hydrogels maintained PCLS architecture (no difference), viability (4.7-fold increase, P  < 0.0001), and cellular phenotype as measured by SFTPC (1.8-fold increase, P  < 0.0001) and vimentin expression (no change) compared with nonencapsulated controls. Collectively, these results demonstrate that hydrogel biomaterials support the extended culture times required to study chronic pulmonary diseases ex vivo using PCLS technology.

The Australian Veterinary Prescribing Guidelines for antimicrobial prophylaxis for surgery on dogs and cats are evidence-based guidelines for veterinary practitioners. Validation of these guidelines is necessary to ensure quality and implementability. Two validated tools, used for medical guideline appraisal, were chosen to assess the guidelines. The terminology from the GuideLine Implementability Appraisal (GLIA) and the Appraisal of Guidelines for Research and Evaluation version 2 (AGREE II) were adapted for use by veterinarians. A two-phase evaluation approach was conducted. In the first phase of the evaluation, the GLIA tool was used by two specialist veterinary surgeons in clinical practice. The results of this phase were then used to modify the guidelines. In the second phase, the AGREE II tool was used by 6 general practitioners and 6 specialists to appraise the guidelines. In phase 1, the specialist surgeons either agreed or strongly agreed that the guidelines were executable, decidable, valid and novel, and that the guidelines would fit within the process of care. The surgeons were neutral on flexibility and measurability. Additional clarity around one common surgical procedure was added to the guidelines, after which the surgeons agreed that the guidelines were sufficiently flexible. In phase 2, 12 veterinarians completed the assessment using the AGREE II tool. In all sections the scaled domain score was greater than 70%. The overall quality of the guidelines was given a global scaled score of 76%. This assessment has demonstrated that the guidelines for antimicrobial prophylaxis for companion animal surgery are valid and appear implementable., (© 2019 Australian Veterinary Association.)

Background: To enable better antimicrobial stewardship, it is important to know what the patterns of prescribing behaviour are and what diseases or reasons antibiotics are being prescribed. A prescribing guideline (i.e. recommended best practice for writing prescriptions) developed by the Australian poultry veterinarians exists. However, it is not a prescribing guideline detailing treatments for the commonly observed bacterial diseases in commercial poultry., Methods: An online survey was deployed to all registered veterinarians and members of the Australian Veterinary Poultry Association to identify prescribing behaviours for the most frequently observed bacterial diseases of poultry., Results: A total of 39 survey responses were received. Most surveys were started but not completed; 13 (33%) were completed with 18 (46%) containing some information on prescribing. The most frequent treatment responses were for Escherichia coli in both layers and broilers, chronic respiratory disease (CRD), fowl cholera and spotty liver in layers and necrotic enteritis in broilers. Treatments described were for products registered for poultry use, within the recommended label dose and duration of treatment (Tables 1, 2). Unsurprisingly, tetracyclines and amoxycillin, followed by lincomycin and trimethoprim sulfonamide products were the most frequently reported treatment options. Inappropriate treatments were reported for salmonellosis and one veterinarian recommended the use of enrofloxacin for the treatment of fowl cholera., Conclusion: Information provided by respondents will enable the initial development of prescribing guidelines for both commercial and small poultry flocks. Importantly, it identified less than optimal prescribing behaviour for some diseases, a reliance on one class of antibiotic more than others and a failure to utilise all antimicrobial classes potentially available for treatment. Critically, the survey identified a lack of treatment options for bacterial disease in poultry. The most important bacterial diseases of poultry remain the same; effective alternatives for antibiotic treatment are required and old diseases, thought once gone, are reinventing themselves as problems for the future. Surveys of prescribing behaviours are essential for identifying diseases of high priority, changes in treatments and response to treatment and to identify areas for targeted antimicrobial stewardship, and research needs., (© 2019 Australian Veterinary Association.)

Background: Appropriate dosing with antimicrobial agents is critical for effective treatment and to prevent the development of antimicrobial resistance., Methods: A review was undertaken of equine journal articles (Equine Veterinary Journal, Equine Veterinary Education, Australian Veterinary Journal, Australian Equine Veterinarian, Journal of Veterinary Internal Medicine and Journal of Equine Veterinary Science) between January 2015 and August 2018. Those with dosing regimens for procaine penicillin G, gentamicin or trimethoprim-sulfonamide in adult horses were examined and evaluated. Pharmacokinetics and -dynamics of these drugs were also reviewed., Results & Conclusion: The most frequently reported doses for penicillin, gentamicin and trimethoprim-sulfonamide were 20-25,000 IU/kg, 6.6 mg/kg and 30 mg/kg, respectively. Veterinarians treating equine patients in Australia should be aware of the current recommended doses and inter-dosing intervals to ensure efficacy in therapy and to preserve the usefulness of these antimicrobials for the future., (© 2019 Australian Veterinary Association.)

Sarcomeric disarray is a hallmark of gene mutations in patients with Hypertrophic Cardiomyopathy (HCM). However, it is unknown when detrimental sarcomeric changes first occur and whether they originate in the developing embryonic heart. Furthermore, Rho Kinase (ROCK) is a serine threonine protein kinase that is critical for regulating the function of several sarcomeric proteins and therefore, our aim was to determine if disruption of ROCK signalling during the earliest stages of heart development would disrupt the integrity of sarcomeres altering heart development and function. Using a mouse model in which the function of ROCK is specifically disrupted in embryonic cardiomyocytes we demonstrate a progressive cardiomyopathy that first appeared as sarcomeric disarray during cardiogenesis. This led to abnormalities in the structure of embryonic ventricular wall and compensatory cardiomyocyte hypertrophy during foetal development. This sarcomeric disruption and hypertrophy persisted throughout adult life, triggering left ventricular concentric hypertrophy with systolic dysfunction, and re-activation of foetal gene expression and cardiac fibrosis, all typical features of HCM. Taken together, our findings establish a novel mechanism for the developmental origin of the sarcomeric phenotype of HCM and suggest that variants in the ROCK genes or disruption of ROCK signalling could, in part, contribute to its pathogenesis.

Chronic pulmonary diseases, including idiopathic pulmonary fibrosis (IPF), pulmonary hypertension (PH), and chronic obstructive pulmonary disease (COPD), account for staggering morbidity and mortality worldwide but have limited clinical management options available. Although great progress has been made to elucidate the cellular and molecular pathways underlying these diseases, there remains a significant disparity between basic research endeavors and clinical outcomes. This discrepancy is due in part to the failure of many current disease models to recapitulate the dynamic changes that occur during pathogenesis in vivo. As a result, pulmonary medicine has recently experienced a rapid expansion in the application of engineering principles to characterize changes in human tissues in vivo and model the resulting pathogenic alterations in vitro. We envision that engineering strategies using precision biomaterials and advanced biomanufacturing will revolutionize current approaches to disease modeling and accelerate the development and validation of personalized therapies. This review highlights how advances in lung tissue characterization reveal dynamic changes in the structure, mechanics, and composition of the extracellular matrix in chronic pulmonary diseases and how this information paves the way for tissue-informed engineering of more organotypic models of human pathology. Current translational challenges are discussed as well as opportunities to overcome these barriers with precision biomaterial design and advanced biomanufacturing techniques that embody the principles of personalized medicine to facilitate the rapid development of novel therapeutics for this devastating group of chronic diseases.

Antimicrobial use in veterinary practice is under increasing scrutiny as a contributor to the rising risk of multidrug resistant bacterial pathogens. Surveillance of antimicrobial use in food animals is extensive globally, but population level data is lacking for companion animals. Lack of census data means cohorts are usually restricted to those attending veterinary practices, which precludes aggregating data from large cohorts of animals, independent of their need for veterinary intervention. The objective of this study was to investigate the exposure of dogs and cats to antimicrobials at a population level. A retrospective cohort study was performed using a novel data source; a pet insurance database. The rate of antimicrobial prescribing, and the rate of prescribing of critically important antimicrobials, was measured in a large population of dogs (813,172 dog-years) and cats (129,232 cat-years) from 2013 - 2017. The incidence rate of antimicrobial prescribing was 5.8 prescriptions per 10 dog years (95% CI 5.8-5.9 per 10 dog years) and 3.1 prescriptions per 10 cat years (95% CI 3.1-3.2 per 10 cat years). Critically important antimicrobials accounted for 8% of all the antimicrobials prescribed over the 4-year study. Cats were 4.8-fold more likely than dogs to be prescribed 3rd-generation cephalosporins. The level of antimicrobial exposure in dogs and cats was less than half that for the coincident human community. Data such as this provides a unique opportunity to monitor antimicrobial prescribing in veterinary medicine, which is a critical component of optimal antimicrobial stewardship., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background and Objective: Noroviruses have been recognised as a significant cause of neonatal enteritis in calves in many countries, but there has been no investigation of their occurrence in Australian cattle. This study aimed to establish whether bovine noroviruses could be detected in faecal samples from Australian dairy cattle. It also sought to determine whether bovine coronaviruses, also associated with neonatal enteritis in calves, could be detected in the same faecal samples., Methods: A selection of faecal samples that were negative for rotaviruses from dairy farms located in three geographically distinct regions of Victoria were pooled and tested by reverse transcription-PCR for the presence of noroviruses (genogroup III), neboviruses and bovine coronaviruses., Results and Conclusion: Genetically distinct genogroup III noroviruses were detected in two sample pools from different geographic regions and bovine coronavirus was detected in a third pool of samples. This is the first report of bovine norovirus infection in Australian cattle and suggests that future work is required to determine the significance of these agents as a cause of bovine enteric disease in Australia., (© 2018 Australian Veterinary Association.)

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., (© 2018 Australian Veterinary Association.)

Background: Antimicrobial stewardship (AMS) programs are yet to be widely implemented in veterinary practice and medical programs are unlikely to be directly applicable to veterinary settings., Objective: To gain an in-depth understanding of the factors that influence effective AMS in veterinary practices in Australia., Methods: A concurrent explanatory mixed methods design was used. The quantitative phase of the study consisted of an online questionnaire to assess veterinarians' attitudes to antimicrobial resistance (AMR) and antimicrobial use in animals, and the extent to which AMS currently is implemented (knowingly or unknowingly). The qualitative phase used semi-structured interviews to gain an understanding of the barriers to and enablers of AMS in veterinary practices. Data were collected and entered into NVivo v.11, openly coded and analyzed according to mixed methods data analysis principles., Results: Companion animal, equine, and bovine veterinarians participated in the study. Veterinary practices rarely had antimicrobial prescribing policies. The key barriers were a lack of AMS governance structures, client expectations and competition between practices, cost of microbiological testing, and lack of access to education, training and AMS resources. The enablers were concern for the role of veterinary antimicrobial use in development of AMR in humans, a sense of pride in the service provided, and preparedness to change prescribing practices., Conclusion and Clinical Importance: Our study can guide development and establishment of AMS programs in veterinary practices by defining the major issues that influence the prescribing behavior of veterinarians., (Copyright © 2018 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.)

Background: Antimicrobials are widely used in Australian veterinary practices, but no investigation into the classes of antimicrobials used, or the appropriateness of use in horses, has been conducted., Objectives: The aim of the study was to describe antimicrobial use for surgical prophylaxis in equine practice in Australia., Study Design: Cross-sectional questionnaire survey., Methods: An online questionnaire was used to document antimicrobial usage patterns. Information solicited in the questionnaire included demographic details of the respondents, the frequency with which antimicrobials were used for specific surgical conditions (including the dose, timing and duration of therapy) and practice antimicrobial use policies and sources of information about antimicrobials and their uses., Results: A total of 337 members of the Australian veterinary profession completed the survey. Generally, the choice of antimicrobial was appropriate for the specified equine surgical condition, but the dose and duration of therapy varied greatly. While there was poor optimal compliance with British Equine Veterinary Association guidelines in all scenarios (range 1-15%), except removal of a nonulcerated dermal mass (42%), suboptimal compliance (compliant antimicrobial drug selection but inappropriate timing, dose or duration of therapy) was moderate for all scenarios (range 48-68%), except for an uninfected contaminated wound over the thorax, where both optimal and suboptimal compliance was very poor (1%). Veterinarians practicing at a university hospital had higher odds of compliance than general practice veterinarians (Odds ratio 3.2, 95% CI, 1.1-8.9, P = 0.03)., Main Limitations: Many survey responses were collected at conferences which may introduce selection bias, as veterinarians attending conferences may be more likely to have been exposed to contemporary antimicrobial prescribing recommendations., Conclusions: Antimicrobial use guidelines need to be developed and promoted to improve the responsible use of antimicrobials in equine practice in Australia. An emphasis should be placed on antimicrobial therapy for wounds and appropriate dosing for procaine penicillin., (© 2017 EVJ Ltd.)