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by Leigh Shelford
Medical and healthcare technology is a key and growing activity at Cambridge Design Partnership, and one of our largest growth areas is diagnostics. Diagnostic techniques and devices are truly interdisciplinary, combining and integrating biological processes with science and engineering disciplines including microfluidics, optics, electronics and more. I am excited and driven by the potential for new diagnostic devices to deliver profound gains in effective and expeditious diagnosis and healthcare. One of the clearest examples of this potential is in the management and stewardship of antimicrobial treatments.
The introduction of antibiotics brought a revolution to healthcare. Infections that posed high risk of mortality became straightforward to treat and perilous medical procedures became almost routine. However, as we often hear, it’s easy to have too much of a good thing…
Bacteria and other microorganisms are adapting and evolving resistance to the very drugs formulated to destroy them. This natural process is accelerating as antimicrobial drugs are used more and more, and in some cases, unnecessarily. Antimicrobial resistance is now a massive global issue, implicated in hundreds of thousands of deaths annually with the figures expected to grow significantly if no action is taken. Antimicrobial resistance will also have a heavy financial impact, with longer hospital stays and increased healthcare costs.
In response there is a mounting global antimicrobial stewardship movement. This movement recognises that development of new antimicrobial drugs cannot provide the complete solution and does not attend to the underlying issues. A full approach requires improving education and awareness, reducing incidences of infection and increasing investment in medicines and diagnosis. New in-vitro diagnostic tools which are fast, accurate and easy to use have the potential to simultaneously make a massive contribution to patient care and to global public health.
Sepsis is a prime example where improving the diagnostic workflow could have a profound impact. Sepsis is caused when an infection in any part of the body spreads leading to systematic inflammation, organ dysfunction and ultimately organ failure. It affects 30 million people per year and causes more deaths than prostate cancer, breast cancer and HIV/AIDS combined1. Sepsis is an emergency and rapid response is essential; the survival rate after treatment in the first hour is 80% but this drops to 30% after six hours2.
The UK National Institute for Health and Care Excellence (NICE) encourages a proactive ‘think sepsis’ approach, recommending broad-spectrum intravenous antibiotics within an hour of the identification of high risk signs. Currently, the diagnosis and pathogen identification required for targeted treatment typically relies on blood culture which can take 2-5 days at a microbiology lab and may be unreliable. Ideally, antimicrobial drugs would be administered only to patients with a positive sepsis diagnosis and targeted at the sepsis-causing pathogens, but waiting for the required clinical information is not an option for a patient at risk of life changing injury, loss of limbs or death. With sepsis, the incentives currently favour rapid use of broad spectrum antimicrobials over concerns antimicrobial stewardship.
New diagnostic tools can shift the balance and simultaneously deliver improved patient care and benefits to public health. For example, rapid and reliable confirmation of the absence of a bloodstream infection could prevent unnecessary use of broad spectrum antimicrobials. Where infection is positively diagnosed reducing the time to pathogen identification (ID) and antimicrobial susceptibility testing (AST) would allow targeted antimicrobial treatment with the optimum antimicrobials as quickly as possible.
Several new sepsis diagnostic technologies are in development which promise to deliver massive benefits over the current workflows. Specific diagnostics and accelerate diagnostics are developing systems which massively speed up the process of pathogen ID and AST. Specific diagnostic’s well plate-based assay identifies microorganisms from their metabolic by-products generated during growth. Pathogen ID and AST are produced from positive blood culture in just 4 hours, reducing the total time from sample to useful clinical information to 15 hours from the current 2-5 days. The FDA-approved Accelerate’s Pheno™ system detects microorganisms optically using fluorescence in-situ hybridisation (FISH) and measures AST by tracking the division rate of individual live cells. The highly automated system requires far fewer user steps, performing automatic sample filtration and dilution. The system produces pathogen ID in 90 minutes and AST in an additional 5 hours.
Other methods may remove the need for blood culture entirely, with pathogens detected and identified by their genetic signature. A system developed by Qvella™ generates pathogen ID directly from whole blood samples in less than an hour with minimum user operation. These genotype tests are likely to be the fastest route to pathogen ID, but lack some of the functionality of the phenotype systems, particularly antimicrobial susceptibility testing.
These and other new in-vitro diagnostic tools will deliver essential clinical information much more rapidly whilst also reducing demands on microbiology staff and facilities. As the trend for increasing speed and automation continues future diagnostic tools are likely to move out of the lab, providing information where it is needed as quickly as possible. Furthermore, the ability to monitor treatment efficacy in real time will increase optimisation of antimicrobial use. New tools may also bring increased functionality; for example, no point-of-care systems currently determine whether infection is of bacterial, viral or fungal origin.
 - Global Sepsis Alliance, WSD factsheet
 - Ref 3 in WSD ‘Golden Hour’ document
15 November 2019
Clare Beddoes & Bastiaan De Leeuw, highlight some of the key learnings from this year’s Parenteral Drug Association (PDA) Europe event.
13 November 2019
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