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Next generation sepsis diagnosis

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A reliable and much faster system for sepsis diagnosis

Prompt sepsis diagnosis remains one of the biggest medical challenges, with every hour of delay in antibiotic therapy increasing mortality. A novel assay can rapidly identify microorganisms in whole blood in under 3 hours.

Health

Sepsis is the result of an exacerbated immune response to infection that may lead to multiple organ failure and death. Sepsis is responsible for 9 million deaths annually. Currently, diagnosis is made by blood culture and nucleic acid-based multiplex technologies. However, these methods are time-consuming (results are produced 1 or 2 days later) and suffer from low sensitivity. Therefore, there is an imminent need for new diagnostic tools to provide more accurate and earlier sepsis diagnosis, so that proper antimicrobial treatment can commence in time.

A new tool for the rapid diagnosis of sepsis

The EU-funded SMARTDIAGNOS project aimed to address this diagnostic gap by bringing together a multidisciplinary team of clinical microbiologists and researchers in molecular biology and nanotechnology as well as diagnostic small and medium-sized enterprises. “Our goal was to develop new systems to diagnose a wide range of pathogens and resistance mechanisms in whole blood in just 3 hours,” explains scientific coordinator Anders Wolff. Identification of the causative microorganism is paramount for administering the correct antibiotic promptly. Patients receiving the right antimicrobials within the first hours of symptom onset, have an 80 % chance of survival. However, for every hour of treatment delay, the survival rate drops by approximately 8 %. To overturn these dismal statistics, the SMARTDIAGNOS consortium had to address the main challenge in sepsis diagnosis, i.e. detection of the low number of microorganisms present in blood. For this purpose, they developed a method based on magnetic-bead-based pathogen concentration. Pathogen identification was undertaken using solid-phase polymerase chain reaction (commonly known as solid-phase PCR), performed on a supercritical angle fluorescence (SAF) microlens array embedded in a microchip. This system enabled quick and accurate detection without the need for enriching the microorganisms with culture. The resulting assay can test for and discriminate among more than 100 sepsis-causing microorganisms, resistance genes and fungi-related genes in whole blood in less than 3 hours.

Successful system evaluation in the clinic – and a versatile technology for further application

As part of the market approval strategy in Europe, the SMARTDIAGNOS system underwent clinical evaluation in a pilot study at the Department of Clinical Microbiology at Unilabs AB in Sweden. This allowed partners to further optimise the newly developed instrument, assess its analytical sensitivity and specificity, and test the study protocols. Analysis of over 400 samples demonstrated 70 % sensitivity and 99 % specificity, while in total, 96 % of the samples were correctly classified within 2 to 4 hours. This showed an obvious improvement compared to the current gold standard method of blood culturing, which required 48 to 120 hours to produce results. “Importantly, the SMARTDIAGNOS technology is scalable and versatile, and can extend beyond sepsis for the diagnosis of other diseases,” emphasises Wolff. Sepsis patients present with heterogeneous symptoms, rendering diagnosis rather difficult. It is also challenging to differentiate sepsis from non-infectious systemic inflammatory response syndrome, which has similar symptoms but requires different treatment. SMARTDIAGNOS will help considerably in achieving correct diagnoses, given its multiplexing capacity. It will also contribute to the detection of antimicrobial resistance genes, improving patient outcome and shortening ICU hospitalisation.

Keywords

SMARTDIAGNOS, sepsis, microorganism, whole blood, blood culture, solid-phase PCR, supercritical angle fluorescence

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