Antimicrobial resistance (AMR) is an increasing worldwide public health problem that can lead to increased morbidity, use of healthcare, mortality, and cost. The UN estimates that AMR could cause 10 million deaths a year by 2050, with costs in the hundreds of billions. A driving force behind AMR is the non-prudent use of antibiotics, so reducing their unnecessary consumption can have an impact on resistance. A variety of actions have been proposed to deal with this, including global awareness campaigns, increasing financial resources for infectious disease in the healthcare sector, the development of new antibiotics, policies aimed at reducing the use of antibiotics, and – as we saw in the last blog of this series – improved diagnostics. The WHO currently considers AMR to be one of the three greatest threats to human health for the next decades.
According to the CDC, antibiotic stewardship is ‘the effort to measure and improve how antibiotics are prescribed by clinicians and used by patients. Improving antibiotic prescribing and use is critical to effectively treat infections, protect patients from harms caused by unnecessary antibiotic use, and combat antibiotic resistance.’
Alongside stewardship, we must also focus on precision antimicrobial prescribing, which will move clinical decision-making from its current one-size-fits-all approach towards tailoring the type and dose of antibiotic given to an individual. To improve antibiotic prescribing, effective strategies must be implemented and aligned with evidence-based recommendations for diagnosis and management. Improved prescribing will lead to better individual outcomes and preserve the effectiveness of existing agents whilst reducing the negative consequences of antibiotic therapy on the individual and society.
In the second blog of our AMR series, we focus on precision prescribing and antibiotics decision-making. We speak to Dr Timothy Rawson, an Honorary Clinical Lecturer in the Department of Infectious Disease, who is also the Research Lead for the Precision Prescribing Theme at the NIHR Health Protection Research Unit in Healthcare Associated Infections and Antimicrobial Resistance (HPRU in HCAI and AMR) and a researcher within the Centre for Antimicrobial Optimisation. We also speak to Dr Nina Zhu (Department of Infectious Disease), who is the Research Lead for the Population Health & Policy Theme in the HPRU in HCIA and AMR.
Tell me about yourself and your research
TR: I am an Infectious Diseases and Medical Microbiology Specialist Trainee in the NHS and Precision Prescribing Research Theme Lead for the HPRU in HCAI and AMR at Imperial College London. I am an affiliate of the Institute for Molecular Science & Engineering, and this year a Reform Scholar for the Think Tank, Reform. I completed my PhD in 2018 on precision approaches to antimicrobial prescribing in secondary care. I have been fortunate to work across medicine, bioengineering, and electrical engineering. I have an interest in optimising antimicrobial prescribing and antimicrobial resistance and the development of technology. This has included working on new artificial intelligence and biosensor technology for precision antimicrobial prescribing and first-in-human medical device studies, implementation of technology in the NHS, and clinical trials of investigatory medicinal products.
NZ: I am the research lead of the Population Health and Policy theme of the HPRU HCAI AMR. My background covers bioengineering, epidemiology, and health economics. My research focuses heavily on improving surveillance for infections and AMR and using data intelligently to assess the impact of health interventions.
What are the key challenges in your research area?
TR: Despite knowing that drug concentration varies widely between patients receiving one-size-fits-all antibiotic dosing in clinical practice, we have very limited ways of routinely measuring and correcting antibiotic concentration in patients. This means that we don’t truly appreciate drug variation and its impact on clinical outcomes and AMR in the real-world.
Within the HPRU’s Precision Prescribing Theme and the Centre for Antimicrobial Optimisation (CAMO), we have developed a study, called DATA-TDM, that aims to address this. DATA-TDM will collect drug concentration data from patients with infection across our NHS hospitals and link this data to the patients’ medical records. This will allow us to apply AI-supported algorithms that can begin identifying patient factors (such as vital signs or blood tests) that describe the patient’s response to observed concentrations of antibiotic being achieved. This will provide insight into who may benefit most from individualised therapy and help us develop new AI-based and biosensor tools to address the most urgent needs. We also hope that this model will facilitate direct patient benefit within the NHS through the information that it generates.
NZ: The key challenges are from the surveillance gaps in resource-limited settings and populations that are socially deprived, with low health literacy or less access to healthcare. These population groups are more vulnerable and have higher risk of contracting infections but there less data is available to help understand what might work for them in terms of interventions and policies.
Where do you see your research going in 5 years’ time?
TR: The goal of our research is to develop evidence and interventions to facilitate the precise and individualised use of antibiotics. Hopefully, by improving the precision of antibiotic prescribing, we can improve patient outcomes, limit side effects, and minimise the impact of antibiotic use on the development of antimicrobial resistance.
Within the precision prescribing theme we aim to:
- Bridge current gaps in our understanding of how variation in drug exposure within individual patients influences treatment outcomes, toxicity, and antimicrobial resistance.
- Develop and implement interventions to support individualised approaches to antimicrobial prescribing (e.g. selection of drug, route, dose, duration).
- Create evidence that can support policy decisions and drive clinical practice.
Within five years, I hope that we will have a clear understanding of how observed drug concentration affects treatment response. This will provide a clear roadmap of patient populations that will most benefit from individualised treatments and the implementation of technology. I hope that we will have validated – and be using in clinical practice – tools and predictive models to help us make individualised treatment decisions around antibiotic treatment. Through the development of evidence and technology to support precision prescribing, I hope that we will have the ability to design clinical trials to evaluate the impact of these approaches on problems like AMR. This will support the UK government’s national action plan on AMR and the WHO AMR research agenda, which have both placed an important focus on the optimisation of antimicrobial use over the next 5 years.
NZ: I have a strong interest in developing better metrics to measure health systems’ performance in addressing AMR, this includes quantifying AMR prevalence in different healthcare sectors and populations, and measuring health service capacity and quality.
What do you perceive as the “origins” of antimicrobial resistance?
TR: Antimicrobial resistance is just part of natural evolution. All life has evolved due to natural selection with genetic mutations / genes that confirm a survival advantage being more readily passed on through generations.
Unfortunately for humans, we create selective pressure in bacterial populations when we prescribe antibiotics to treat infections. There is not one antibiotic where we haven’t observed the emergence of resistance to it after has started being used.
Whilst we can’t stop the inevitable emergence of resistance to an antibiotic, we can develop methods of minimising and slowing down the selection of AMR to maintain the effectiveness of our antibiotic within a population. This is why precision prescribing is vital, as without a better way of treating the individual infection, we continue to overprescribe treatments, increasing the selection pressure for the emergence of drug-resistance.
NZ: I would say inappropriate use of antimicrobial drugs is one of the major drivers, this includes under-use and over-use. Also, we are exposed to antimicrobials from food and environmental sources so a One Health approach is key.
Where do you think Imperial’s strengths lie in this field?
TR: Firstly, Imperial has an incredible pedigree in infectious diseases research. Penicillin was discovered at St Mary’s Hospital by Sir Alexander Fleming and through the last century, Imperial has been at the cutting edge of infectious disease research. Currently, in the field of AMR – led by Professor Alison Holmes – we have had the HPRU in HCAI and AMR that has been running since 2014 and recently the Wellcome Trust funded Centre for Antimicrobial Optimisation Network (CAMO-NET), a multinational collaboration to develop and implement technologies to tackle AMR.
In terms of technology development and translation, Imperial’s excellence in bioengineering, electrical engineering, chemistry, and maths has allowed for collaborations to be established across disciplines with numerous joint PhD projects and programme grants facilitating a truly collaborative approach.
The Imperial College Academic Health Science Centre, a collaboration between Imperial College London and Imperial College Healthcare NHS Trust, has provided a platform for identifying clinical need and then rapidly developing and translating solutions back into the clinic. This has been further supported by the Imperial Biomedical Research Centre and its support of projects such as iCARE (Imperial Clinical Analytics, Research and Evaluation) team, which has allowed the improved use of patient data as part of research projects.
NZ: AMR is far more complex than a medical problem, the strengths of Imperial lie within the multidisciplinary capacity and close connections with policymakers and health practitioners – this means research is guided by the patient and public needs and evidence can be translated to clinical practice rapidly.
What solutions would you like to see in the future?
TR: I hope that in the future we can adopt technologies that will allow us to rapidly assess individual patient drug concentrations and response to treatment in real-time, allowing us to make personalised treatment decisions. I hope that we can create wider networks of data generation, like the DATA-TDM study, that will allow us to develop better predictive models and enhance our understanding of the impact of factors, such as drug exposure, on different aspects of treatment outcome, toxicity, and the development of AMR.
My real hope is that developing technologies and new approaches to the treatment of infections using tools that provide us with better, more real-time data will allow us to be more precise and accurate in the way that we use antibiotics. This will hopefully not only improve outcomes for patients but help us safeguard our current and future antibiotic treatments.
NZ: I definitely want to see the increased public awareness of AMR, around how each one of us in the society can help combat this serious public health threat. And more interdisciplinary research for instance, AMR and nutrition and food science, AMR and maternal and child health etc.
How important is an interdisciplinary approach to AMR research?
TR: Having worked within the HPRU and as part of CAMO over the last 8 years, I have seen the importance of interdisciplinary approaches to AMR first hand. AMR is a complex and multifaceted problem that requires interdisciplinary skills to solve. Creating environments to support truly interdisciplinary collaboration can enhance our ability to approach a problem from different points of view. It can help develop broader skills and understanding of the problem and ensure that interventions are developed grounded in a solid understanding, with expert skill, and then support implementation and adoption in the area with the greatest clinical need. I think that the environment created by Professor Holmes at Imperial and now internationally through CAMO-NET has been an incredible example of how this can be used effectively to address AMR.
NZ: Extremely, as I mentioned before, AMR is more than a clinical problem, it requires research that spans from molecular biology to understanding the resistant genes all the way to psychology to improve clinicians’ decision-making and patients’ care-seeking behaviour. In my area, good disease surveillance and data requires expertise from statistics, mathematics, computer science and engineering. For instance, mathematical modelling has been commonly used in infectious disease research for decades, but more recently, approaches from other disciplines such as systems engineering, and econometrics have also been used to develop better epidemiological models. Also, addressing AMR requires a One Health approach of which specialists from veterinary, environment, agriculture and aquaculture are just as important as the ones for human health.
Are you optimistic that we can successfully overcome the challenges posed by AMR?
TR: I think that the challenge of AMR is something that we are going to be facing in one form or another for as long as we rely on antibiotics for the prevention and treatment of infection. I am optimistic that we are moving in the right direction towards mitigating its impact. By being smarter with how we use data, developing new interventions (whether diagnostics, treatments, or tools to be more precise with how we use agents), being more individualised in our approach to treatment, and focusing on improving patient and prescriber attitudes and behaviours towards antimicrobials, I hope that we will be able to mitigate the impact of AMR on patients and maximise the efficacy of treatments that we have available to us now and in the future.
NZ: Yes, despite all the challenges, I’m optimistic. AMR has become a public health priority worldwide. The COVID-19 pandemic has slowed global progress in addressing it, but there’s increased public awareness around infection prevention, hand hygiene, genomics. Also, I have seen experts from other disciplines, particularly the younger generations, start to work in AMR. So overall, I feel optimistic.