Using data to tackle antimicrobial resistance: Insights from the Small Animal Veterinary Surveillance Network (SAVSNET). Guest blog by David Singleton
Using data to tackle antimicrobial resistance: Insights from the Small Animal Veterinary Surveillance Network (SAVSNET)
The world certainly does not seem lacking in doom-laden scenarios right now. Dire climate change predictions being made by climatologists at the COP-26 in Glasgow, made worse by seemingly lacklustre responses from the world’s politicians, the threat of terrorism once more on the rise, and more domestically, questions as to whether there will be enough toys on the shelves for Christmas… all of course presided over by the spectre of COVID-19 that continues to haunt us, potentially for years to come. It might therefore seem not particularly welcome that this article discusses yet another potentially apocalyptic topic: antimicrobial resistance (AMR). However, as we approach the season of good cheer, there are at least some recent developments in this area that are worthy of raising a glass or two come the festive period!
The solution and the resulting problem
Antimicrobials are arguably the most important group of medicines developed in the 20th century, enabling previously fatal bacterial infections to be easily and cheaply treated across the globe, also heralding a new era in surgical possibilities, from hip replacements to heart transplants. This medical marvel has, however, been tempered by the evolutionary response by the bacteria we are seeking to destroy. Simply put, the more we use antibiotics, the greater the ‘selection pressure’ we place on bacteria, encouraging evolution of bacteria capable of resisting the effects of antimicrobials… in other words, the more we use these important drugs, the less effective they become. Unfortunately, resistant infections have now become a feature of clinical reality, with clinicians being forced to use so-called ‘last resort’ antimicrobials, which themselves have been associated with mounting resistance.
AMR is of course a true ‘one health’ issue. Use of antimicrobials in people and animals provides the driver for resistance development and dissemination into the environment, thereby increasing the probability of humans and animals suffering from resistant infections. Thankfully, in response, countries around the world have joined in efforts to, in essence, develop interventions that seek to ‘out run’ the bacterial evolutionary process. Many of these efforts are ambitious, including developing new antimicrobials or vaccines, and do carry promise for providing sustainable solutions to the issue of AMR. However, such developments also take considerable time and money, so for now much work has centred around ‘antimicrobial stewardship’, a general term used to describe any efforts to preserve the efficacy of the antimicrobials we already possess.
It would be easy to view AMR as one amorphous blob. However, in reality there are many, many bacterial species capable of causing infections in people or animals, and many antimicrobials already developed to treat such infections. While all antimicrobials and bacterial infections are important, there are some that are causing particular concern now, so much so that the World Health Organization has created a list of the ‘highest priority critically important antimicrobials’ (HPCIAs), which are considered the most important antimicrobials we have, whose efficacy must be preserved at all costs (WHO, 2019). The WHO has also produced a comparative list for resistant infections, hopefully focusing minds on what particularly needs tackling right now (WHO, 2021).
So, what about veterinary data?
To recap, we know that AMR is a ‘one health’ problem. We know that countries around the world are joined in developing solutions to the problem. We also know that some antibiotics are considered of greater importance in terms of preserving their efficacy, and that some resistance trends are particularly worrying to us at the moment. We haven’t, however, talked about how all this impacts on veterinary practice, nor how we can survey the current landscape for new AMR threats, or assess the impact of new stewardship interventions on clinical practice. Even more simply, how do we even know if there is an AMR problem in veterinary species in general, and specifically in companion animals?
Over recent years, access to and use of veterinary electronic health data for research and surveillance has encountered somewhat of a revolution, with projects such as SAVSNET (liverpool.ac.uk/savsnet/) and Vet Compass (rvc.ac.uk/vetcompass) leading the way in harnessing large volumes of veterinary practice and diagnostic laboratory data across the UK and other countries too. These projects have outlined a number of revelations, revealing that antimicrobials are commonly prescribed in up to 20% of appointments at primarily first-opinion clinics (Buckland et al, 2016; Singleton et al, 2017), with such prescriptions frequently being made with limited justification being recorded in clinical notes (Burke et al, 2017), for a diverse range of conditions for which the justification for prescribing antimicrobials is limited (Singleton et al, 2019). Most troublingly, however, it has been found that antimicrobials which are considered of critical importance by the WHO, are also routinely prescribed in companion animals. In fact, in cats, cefovecin (a 3rd generation cephalosporin) has been identified as the single most commonly-prescribed antimicrobial agent (Buckland et al, 2016; Singleton et al, 2017), raising real questions about the current veterinary commitment to responsible use of antimicrobials.
One might argue that such findings are of little consequence if no impact on resistant infections is being seen in practice. However, recently published evidence suggests that multi-drug resistance is being commonly encountered in practice, including resistance to such ‘last resort’ antimicrobials as discussed earlier (Singleton et al, 2021). It is likely that as AMR continues to disseminate that, much like the rising tides associated with climate change, if practitioners are not already experiencing issues with resistant infections, such problems are only just around the corner.
I thought you said this wouldn’t be all doom and gloom?!
At this point things will start to take on a sunnier outlook – I promise! Gladly, such troubling findings have, so far, prompted a strong and positive reaction from the companion animal veterinary community, with several large practice-owning groups and many independent veterinary practices placing antimicrobial stewardship at the centre of their efforts to improve care quality. One such group, CVS, approached SAVSNET seeking assistance with enacting their own ideas. We quickly realised that the ideas being discussed were untested in the veterinary sector, and so a randomised controlled trial seeking to prompt voluntary changes in antimicrobial prescribing behaviour was born.
We started with CVS veterinary practices that were identified by SAVSNET as above average prescribers of HPCIAs. They were randomly placed into three trial arms: a control group, light intervention group and heavy intervention group, with 20 veterinary practices in each group. Light and heavy intervention groups were informed of their outlier status and were offered either remote (light group) or in-person (heavy group) support, in addition to their existing access to the SAVSNET portal, which offers free benchmarking for antimicrobial prescription. CVS practice teams in the heavy group were asked to reflect on their HPCIA prescription and clinical decision-making to develop their own systems to promote responsible prescribing, and were supported in enacting change over a 6-month period.
The results
In truth, the results really surprised us – it turns out that there is a massive appetite for stewardship in veterinary practice! Over 8 months following initial intervention, both intervention groups were associated with a significant post-intervention decrease in HPCIA prescription frequency in cats; the light group by 17% and the heavy group by 40%. In dogs, the only significant decrease was seen in the heavy group, which decreased HPCIA prescription frequency by 23%.
This trial shows that companion animal veterinary practitioners respond to notification of being outside of a 'social norm' (i.e. being an above average HPCIA prescriber), and are responsive to involvement in structured antimicrobial stewardship programmes. It also suggested to us that ‘friendly’ (that is, not legislative) approaches to stewardship can work, and that busy professionals are more than willing to voluntarily engage with improvement processes, even if it has significant impacts on their time. We were fortunate to publish this work in Nature Communications, which can be accessed here: https://www.nature.com/articles/s41467-021-21864-3.
What next?
Well, we certainly learnt a lot from this trial, and we hope the practitioners involved did too. Work is now ongoing, in collaboration with RCVS Knowledge, to bring these learnings to a national level – watch this space. More widely, focus on companion animal stewardship continues to reach greater levels of prominence, and the ‘Responsible Usage of Medicines in Agriculture’ Alliance (RUMA), a group credited as being a key player in encouraging significant sector-wide reductions in antimicrobial use in agriculture, has recently announced a new group, which will focus on companion animals and horses. Their newly launched website can be seen here (http://rumacae.org.uk/), and I’m excited to see what this group produces in the future. With such initiatives now starting to reach the profession, we are optimistic that positive impacts on AMR will be made.
References
Buckland, E. L. et al. (2016). Characterisation of antimicrobial usage in cats and dogs attending UK primary care companion animal veterinary practices. Vet Rec 179, 489.
Burke, S. et al. (2017). Use of cefovecin in a UK population of cats attending first-opinion practices as recorded in electronic health records. J Feline Med Surg 19, 687-92.
Singleton, D. A. et al. (2017). Patterns of antimicrobial agent prescription in a sentinel population of canine and feline veterinary practices in the United Kingdom. Vet. J. 224, 18-24.
Singleton, D. A. et al. (2019). Pharmaceutical prescription in canine acute diarrhoea: A longitudinal electronic health record analysis of first opinion veterinary practices. Front. Vet. Sci. 6,
Singleton, D.A. et al. (2021). Temporal, spatial, and genomic analyses of Enterobacteriaceae clinical antimicrobial resistance in companion animals reveals phenotypes and genotypes of one health concern. Frontiers in Microbiology 12: 2160.
WHO. (2019). Critically important antimicrobials for human medicine. https://www.who.int/publications/i/item/9789241515528
WHO. (2021). Global priority list of antibiotic-resistant bacteria to guide research, discovery, and development of new antibiotics. https://www.who.int/medicines/publications/WHO-PPL-Short_Summary_25Feb-ET_NM_WHO.pdf
David Singleton BVSc MSc PhD MRCVS, University of Liverpool.
David is a veterinary surgeon with a Master's degree and PhD in epidemiology and health informatics, currently working as a research fellow in infectious disease epidemiology at the University of Liverpool, United Kingdom. He is passionate about how data can be harnessed and safely used to revolutionise both veterinary and medical practice, and has experience of using data to motivate positive practitioner behavioural change. His particular area of interest is antimicrobial resistance. He is currently exploring the impact of vaccination on antimicrobial prescription and resistance, using routinely collected electronic health data in the UK and via vaccine implementation trials in Malawi.