Direct from blood
Direct-from-blood multiplex PCR targeting 95% of sepsis-causing pathogens
Early detection represents our best chance of reducing the significant morbidity and mortality associated with sepsis. At deepull we are developing technology to empower hospitals to do something never done before: provide 50 reportable results identifying pathogens and antibiotic resistance markers directly from blood in about 1 hour.
Product under development. Not currently available for diagnostic use.
What is sepsis?
Early detection represents our best chance of reducing the significant morbidity and mortality associated with sepsis. At deepull we are developing technology to empower hospitals to do something never done before: provide 50 reportable results identifying pathogens and antibiotic resistance markers directly from blood in about 1 hour.
Sepsis is hard to define and even harder to diagnose. The most current literature defines sepsis as a life-threatening organ dysfunction caused by a dysregulated host response to infection1. If untreated, this can lead to septic shock which is a dramatic drop in blood pressure that damages organs. In severe cases this can lead to death.
Every year about 49 million people are diagnosed with sepsis and about 11 million die across the globe2. The U.S. CDC estimates that sepsis contributes to 1 of every 3 hospital deaths3.
Early detection and effective antibiotic treatment are key to combatting sepsis. However, early diagnosis remains a challenge as the early symptoms of sepsis are non-specific and easy to miss such as: fever, increased heart rate, confusion, and low-blood pressure. Furthermore, confirming and identifying the underlying infection is a complicated and time-consuming task for the hospital laboratory.
The need for faster, more sensitive diagnostic technology has been a recognized unmet medical need for decades. This is the challenge that inspired the inception of deepull.
1) Definition of Sepsis: Singer, et al. The Third International Consensus Definition for Sepsis and Septic Shock (Sepsis-3). JAMA February 2016
2) Rudd, et al. Global, regional, and national sepsis incidence and mortality, 1990-2017: analysis for the Global Burden of Disease Study. Lancet (London, England). 2020;395(10219):200-11
Blood culture-based pathogen identification has demonstrated limitations
Current sepsis guidelines recommend 1-hour and 3-hour bundles. Compliance with these guidelines, however, remains a significant challenge because blood culture-based pathogen identification can take days and only detects viable organisms.
Critical patient management decisions must be made during this time of "diagnostic blindness."
- Should the patient be admitted? Transferred to ICU?
- Should antibiotics be started? Which ones?
Diagnostic delays
contribute to poor patient
outcomes
Studies have shown:
- Initial therapy is inadequate for 1 out of 5 septic patients1
- Sepsis contributes to 1 out of 3 hospital deaths2
- Mortality rate of 30-40% for patients with septic shock3,4,5
- Overuse use of antibiotics drives antimicrobial resistance6,7,8
- Overtreatment may be associated with a 20% increase in odds of death1
- Undertreatment may be associated with a 40% increase in odds of death1
The Surviving Sepsis Campaign 2021 guidelines
The Surviving Sepsis Campaign 2021 guidelines1 contain the following recommendations:
- Antimicrobials should be administered within 1 hour of recognition of patients with definite or probable sepsis.
- Antimicrobials should be administered within 1 hour of recognition of patients with possible sepsis if shock is present.
- Antimicrobials should be administered within 3 hours of recognition of patients with possible sepsis if shock is absent and if concerns for infection persist.
- Rapid assessment of infectious vs. non-infectious causes for patients with possible sepsis if shock is absent should be completed within 3 hours of presentation.
- Use of procalcitonin plus clinical evaluation to decide when to start antimicrobials is not recommended for patients with suspected sepsis or septic shock.
1) https://www.sccm.org/Clinical-Resources/Guidelines/Guidelines/Surviving-Sepsis-Guidelines-2021
References
1) Rhee et al. Prevalence of Antibiotic-Resistant Pathogens in Culture-Proven Sepsis and Outcomes Associated with Inadequate and Broad-Spectrum Empiric Antibiotic Use. JAMA April 2020
2) https://www.cdc.gov/sepsis/about/?CDC_AAref_Val=https://www.cdc.gov/sepsis/what-is-sepsis.html (March 2024)
3) Paoli et al. Epidemiology and Costs of Sepsis in the United States-An Analysis Based on Timing of Diagnosis and Severity Level. CCM December 2018
4) Schoenberg et al. Outcome of patients with sepsis and septic shock after ICU treatment. Langenbecks Arch Surg. March 1998
5) Bauer et al. Mortality in sepsis and septic shock in Europe, North America and Australia between 2009 and 2019— results from a systematic review and meta-analysis. Critical Care May 2020
6) Wonderink, et al. Antibiotic Stewardship in the Intensive Care Unit. An Official American Thoracic Society Workshop Report in Collaboration with the AACN, CHEST, CDC, and SCCM. Ann Am Thorac Sox May 2020
8) Levy, et al. Antibacterial resistance worldwide: causes, challenges and responses. Nature Medicine. November 2004
Standard of care blood culture testing lacks sensitivity
The diagnostic value of blood culture is limited to viable organisms. This restricts positive results to blood samples that contain bacteria and yeast capable of reproduction in incubated blood culture media.
Detected by
blood culture
blood culture
Viable organisms
Non-viable organisms
Fastidious organisms
Microbial cell-free DNA
Total microbial DNA
The diagnostic value of blood culture is limited to viable organisms. This restricts positive results to blood samples that contain bacteria and yeast capable of reproduction in incubated blood culture media. However, the use of highly sensitive molecular techniques creates further diagnostic value by detecting additional bacterial elements that can be found in blood:
Non-viable organisms
Most bacterial cells in blood are dead or otherwise damaged (such as phagocytized microorganisms) and no longer capable of reproduction. Studies have shown that quantitative bacterial load measured by PCR correlates with disease severity and poor patient outcomes.1,2
Fastidious organisms
Some microbiologic species have a very complex or a very narrow set of nutritional requirements. These fastidious organisms will only grow when specific nutrients are included in the medium. These organisms can be particularly difficult to detect in blood culture systems which are inherently dependent on bacterial growth and include media designed to support growth in a broad range of bacterial species. PCR based approaches do not share this limitation.
Microbial cell-free DNA
Microbial cell-free DNA has emerged as a valuable target for identification of pathogens when traditional methods fail to identify the causative agent.3
1) Linoj Samuel, Direct-from-Blood Detection of Pathogens: a Review of Technology and Challenges, JCM 2023 Jul; 61(7): e00231-21
2) Bacconi, et al. Improved Sensitivity for Molecular Detection of Bacterial and Candida Infections in Blood. JCM. September 2014 52(9):3164-74. doi: 10.1128/JCM.00801-14
3) Thompson et. al., Utility of Plasma Microbial Cell-Free DNA Testing for Therapeutic Management and Antimicrobial Stewardship, Open Forum of Inect. Dis. 2023 Dec; 10(Suppl 2): ofad500.1059.
UllCORE System
- Extracts total microbial DNA
- Allows continuous loading for up to 8 samples
- Can prioritize STAT samples
- Handles sample volumes of 0.1 to 10 mL
- Automates sample-to-result testing
- Completes a test in about 1 hour
- Utilizes room temperature stable reagents
- Offers LIS connectivity
- 21-inch height adjustable user interface
- Footprint 100 cm X 75 cm
Product under development. Not currently available for diagnostic use.
UllCORE BSI Test
deepull is developing the UllCORE BSI Test for 8 mL of whole blood from patients with suspected infection or sepsis. Preliminary results based on prospectively obtained specimens from septic patients show:
- High concordance with positive blood culture
- Detection of more than twice as many clinically relevant pathogens compared to blood culture
~1 hr
Turnaround time
Potential clinical benefits of the UllCORE BSI Test
Inform initial therapy decisions
Early administration of appropriate therapy may reduce the risks associated with both overuse and underuse of antibiotics and lead to better patient outcomes.
Compliance with sepsis guidelines
The Surviving Sepsis Campaign 2021 guidelines recommend administration of antimicrobials within 3 hours of recognition of patients with possible sepsis if shock is absent and if concerns for infection persist.
Guide antibiotic stewardship desicions
Minimizing patient exposure to broad spectrum empiric antibiotic therapy as well as targeted therapy are foundational principles of good antibiotic stewardship.
About us
At deepull, we are inspired by the challenge of building novel diagnostic products to meet unmet medical needs.
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Our values
We are driven by integrity and respect for all our stakeholders
For our customers
We empower hospital laboratories to provide faster, more comprehensive results to healthcare providers for improved patient care. Our products must be fairly-priced to impact our communities.
For our employees
We provide an inclusive and open work environment respecting diversity and recognizing individual merit. Employees must feel free to make decisions, take action, offer suggestions and voice concerns.
For our shareholders
We are building a profitable business by promoting innovation and developing high-quality products that address unmet medical needs, are safe and environmentally clean.