Since the golden age of antibiotics we have continued to underappreciate the genetic capabilities of the bacteria we have been trying to kill. The alarming rise in drug-resistant hospital and community acquired bacterial infections is a major public healthcare problem, which is fuelled by the inappropriate use of antibiotics. Antimicrobial resistance (AMR) has been at front of mind for global health leaders, with the 2016 O'Neill Report suggesting that it could cost the global economy more than 100 trillion USD in lost output by 2050 if resistance is not controlled. Professor Dame Sally Davies, the Chief Medical Officer for England, has also publicly warned that antibiotic-resistant bacteria are becoming increasingly difficult to treat.
Rapid diagnostic testing
One of the ways we can help to reduce the misuse of, and development of resistance to, antibiotics is by developing rapid diagnostic tests that not only identify the bacteria causing the infection, but also inform us of its profile.
i-sense is an EPSRC-funded Interdisciplinary Research Collaboration (IRC) engineering new tools and technologies to help track, test and treat infectious diseases. Part of i-sense research is developing mobile phone-connected diagnostic tests to improve early detection and identification of bacterial infections, including MRSA, C. difficile and E. coli.
The current landscape
Current gold standard methods to detect and identify bacterial infections have remained unchanged for decades. These methods are limited by a slow time to result and there is therefore a need for an early detection system, based on rapid diagnostic tests that require few steps to produce a result. Better diagnosis of patients will help to get the correct drug to the patient (antibiotic stewardship) and break cycles of transmission in the community, for example in care homes.
Helping combat AMR with rapid diagnostics
i-sense researchers from UCL, Newcastle University and Brighton and Sussex Medical School (BSMS) are working collaboratively across projects to deliver rapid diagnostic tests for AMR that are suitable for use at point-of-care (PoC). These projects aim to track outbreaks through real-time monitoring of infectious disease, test for bacterial infections and resistance to antibiotics faster than current gold standard, and understand the mechanism of action of new antibiotics to ensure patients are provided the right treatment. Some of these projects include:
- Harnessing the power of developments in computer technologies, particularly cloud computing, to develop 'connected' sensor technologies for PoC use. The data collected can be streamed to a PoC device over the Internet to a Cloud server where a workflow can be executed to provide a diagnosis. In the future, data from multiple sources (other PoC devices, reference laboratories, social media and web searches) can help make diagnostic decisions, which will have major implications for epidemiology, offering the scenario of real-time monitoring of infectious disease outbreaks.
- Developing novel tools to detect drug resistant bacterial infections using nanotechnology. Current methods to measure antibiotic resistance requires waiting for bacterial growth to indicate resistance/susceptibility to antibiotics. Detecting this response sooner can be aided by nanotechnology: i-sense researchers are developing devices that incorporate nanosensors to measure resistance to antibiotics faster than gold standard methods.
- Integrating sequencing technology with connectivity to detect resistance in patient samples, such as tuberculosis (TB), letting a healthcare worker know the right antibiotics to use for treatment of a patient. These tools, which are at a very early stage of research, are small and portable, which means they can be used outside of the traditional laboratory facilities.
- Understanding the mechanism of antibiotics to develop new targets that are difficult for bacteria to develop resistance against, with the hope that we can use them to treat resistant infections. This is done through the use of a high-resolution imaging technique (atomic force microscopy or AFM) that allows us to watch, in real-time, what happens to the surface of bacteria when it is attacked by antibiotics. We can then understand how they work on real bacteria and target them more efficiently. All of this information is important when trying to help fine tune their development, but ultimately you need this information to aid their transition into clinical use.
- Using nanosensors to understand the mechanism of action of new antibiotics, called oritavancin, which contributed to its approval for use in patients.
Exploring the use for i-sense tools and technologies in care homes
i-sense researchers at Newcastle University are working in collaboration with the Brighton and Sussex Medical School (BSMS) to explore the potential for use of our tools and technologies in a care home setting through qualitative research. Care homes are a focus because of their largely hidden and vulnerable population served by multiple visiting health professionals. The study is looking at the current use of PoC diagnostics to understand how these tests could potentially be used to help decision making for C. difficile and MRSA, the benefits and challenges to healthcare professionals in using such tests, and at what points in the care pathway these tests could be useful.
Why are diagnostics important for AMR?
Developing new antibiotics is very important, but using our existing armoury of antibiotics more effectively to prolong their use and reduce the emergence of resistance is equally as important.
Antibiotics are only effective when used for bacterial infections (not for viral infections) and when the right antibiotic is used. Misuse of this medication is leading to bacteria becoming resistant to treatment.
To understand the right treatment for the right patient at the right time, developing better diagnostic tools is crucial. This information is needed as fast as possible and i-sense researchers are at the forefront of developments into rapid diagnostics to help aid this process.
In the last year, the UK has further reduced the antibiotics it prescribes, but this is not necessarily the case for other countries. Reducing AMR is a global effort and it is important that public health agencies can track the emergence of resistance so that efforts can be targeted.
The future of connectivity in healthcare
i-sense places a strong emphasis on the connectivity component of diagnostic tests so that their results can be used to aid a public health effort to protect populations from the spread of AMR and monitor the emergence of resistance.
Antibiotic resistance is a serious global issue, and there is a concerted effort to tackle the issue. Developing new antibiotics and diagnostic tests remains challenging, requiring intensive research and continued funding.