Sepsis – The innovation gap

Sepsis Awareness Month takes place every September. It was established in 2012 by the Global Sepsis Alliance to raise awareness of the condition and provide an opportunity for the world to unite in the fight against it.

Sepsis is a life-threatening organ dysfunction, caused by over activation of the body’s immune system in response to infection¹.

A study by the Global Burden of Disease estimated that one in five deaths were attributable to sepsis in 2017², and of the 49 million cases, almost half occurred in children under five².

Time is of the essence

Effective treatment of sepsis requires a rapid response. Currently available diagnostic tests are limited in their ability to provide a timely diagnosis, and so antibiotics are typically administered prior to a confirmed diagnosis in cases of suspected sepsis.

The over- and mis-prescription of antimicrobials is a key factor contributing to rising antimicrobial resistance (AMR)³ globally.

Rising rates of AMR have a direct impact on the successful treatment of sepsis⁴, but there also remain distinct diagnostic barriers to advancing the clinical management of sepsis.

Antimicrobials should be given within one hour of diagnosis

Diagnosing sepsis is clinically challenging⁵. Sepsis patients typically have an underlying disease-causing infection and therefore symptom severity and type can vary, making it difficult to reliably ascribe symptoms to sepsis.

Current guidelines can lack the level of specificity needed for reliable detection⁶. As well as physical symptoms, sepsis can also elicit a complex physiological response. In short, there is not an isolated inflammatory biomarker indicative of diagnosis⁷.

The Sepsis Campaign

The Sepsis Campaign guidelines recommend the administration of antibiotics within one hour of diagnosis or suspicion of sepsis⁸. For every hour that treatment is delayed, patient mortality rate is estimated to increase by almost 8 percent⁹.

Currently, the most common method for diagnosing sepsis is by sending blood samples to a laboratory for pathogen identification¹⁰. This approach, with an average processing time of 72 hours, is limited in its effectiveness at informing rapid treatment decisions.

AMR Voices Report

The required response of rapid administration of antibiotics threatens further complications to patient health and rising AMR.

In our AMR voices report, we heard from Ronda Windsor, a patient whose surgery for endometriosis led to a urinary tract infection (UTI) that developed into urosepsis¹¹.

Ronda’s urosepsis was treated with broad-spectrum antimicrobials however Ronda now has a chronic, multidrug resistant UTI.

This highlights the importance of rapid detection and response whilst highlighting the implications of non-targeted treatment.

85% sepsis cases and deaths occur in LMICs

The majority of sepsis cases and related deaths occur in low- and middle-income countries (LMICs), and a higher prevalence of AMR is seen in these regions ^2,4.

Despite this, most research on sepsis and its diagnosis is focused on high-income countries with limited relevance elsewhere^12,13.

For example, the higher prevalence of sepsis in some LMIC settings has been linked to a high number of HIV and immunocompromised patients in these regions¹⁴. Current diagnostic approaches and clinical guidelines however do not reflect these patient pathogen profiles and therefore have limited applicability to these populations¹⁵.

Understanding epidemiological and contextual factors across use settings is key for diagnostic innovators looking to advance the clinical management of sepsis in an equitable manner.

Innovation in sepsis diagnostic tests shows promise

Despite the significant barriers innovators face in developing equitable, accurate and rapid diagnostic tests, recent innovations show high potential for improving sepsis diagnosis and treatment.

Rapid molecular diagnostic tests are being developed that focus on detection of specific innate response and cytokine biomarkers, with the aim of offering an immediate snapshot of a patient’s immune state¹⁶. Triage tests are also being developed that aim to map the genotypic profile of a patient’s condition¹⁶.

Nanotech biosensors

Further advances come in the form of nanotechnology-based biosensors that can generate signals based on biochemical markers within patient samples. Biosensors have the potential for monitoring an array of biomarkers, as well as the patient’s immune response in real time¹⁷.

Equitable access to future innovative diagnostic tools focused on timely diagnosis and targeted treatment is paramount to advance the clinical management of the condition where this is most needed.

Sepsis Awareness Month activities and resources

• What is Sepsis? – Sepsis Alliance
• Things you should know – Sepsis Alliance
• FAQs – Sepsis Alliance
• Professional Resources – The UK Sepsis Trust
• Surviving Sepsis Campaign Guidelines 2021 – Society of Critical Care Medicine

More for Sepsis Awareness Month

Dr Ben Morton is a Senior Clinical Lecturer and Honorary Consultant in Critical Care Medicine at the Liverpool School of Tropical Medicine,

He speaks with us about his experience of diagnosing and treating sepsis and the key challenges diagnostic innovators face in tackling the global burden.