A recent poll highlights growing interest in host response testing for sepsis. Immunexpress CEO Rollie Carlson discusses the findings and the future of rapid diagnostics.
In a recent poll conducted by Immunexpress following a Sepsis Alliance webinar, 73% of healthcare professionals and patient advocates said they believe host response testing can help guide antibiotic stewardship efforts.
The results also revealed a concern among respondents that many patients suspected of sepsis are being overdiagnosed and overtreated.
Rollie Carlson, PhD, CEO of Immunexpress, offers a perspective on what the poll results reveal about clinician attitudes, how technologies like SeptiCyte RAPID aim to support faster and more accurate diagnosis, and why improving sepsis detection remains a critical component of combating antimicrobial resistance.
Carlson also discusses where sepsis testing is headed, including the role of personalized approaches and next-generation diagnostics.
Q: What was the purpose of the online poll, and how is Immunexpress planning to use the results?
The audience for these seminars is typically highly educated, with up to 80% of respondents participating in their hospital’s sepsis program. We wanted to understand their familiarity with host response testing and, more importantly, if there was confidence that this could impact antimicrobial resistance (AMR).
Given this, the results were very encouraging as these healthcare professionals demonstrated a familiarity with host response testing. Survey respondents were open to learning more about a test like SeptiCyte RAPID and how it can enhance their sepsis programs with earlier identification of sepsis and appropriate intervention with the goal of improving antibiotic stewardship. This helps guide our outreach to hospital systems considering adopting host response tests.
Q: Were you surprised that respondents believed patients were being overtreated—meaning they were also being overdiagnosed?
We were somewhat surprised at this admission, but perhaps it occurred because the poll was anonymous. Most hospitals have sepsis alerts which are overly sensitive, which leads to many patients with suspected sepsis being worked up through the sepsis bundle, which includes administration of antibiotics.
In fact, the most recent Surviving Sepsis Campaign 2021 sepsis and septic shock clinical management guidelines are working to address overtreatment, but overtreatment still remains an issue that healthcare professionals themselves are willing to acknowledge, at least anonymously.
Q: The SeptiCyte test is designed for in-hospital use. How does this differ from other tests used in the ED, for example?
SeptiCyte RAPID is the only commercially available test that can accurately differentiate sepsis from non-infectious systemic inflammation in patients suspected of sepsis. This includes patients with challenging comorbidities, such as neutropenic, immunocompromised, post-surgery patients, or patients with burns. Other tests that are used in the ED—for example C-reactive protein, procalcitonin, and white blood cells—are non-specific.
While these tests can help in the clinical assessment of the patient, it should be noted that they cannot specifically identify sepsis or differentiate it from non-infectious systemic inflammation. Clinical evidence for SeptiCyte RAPID performance is voluminous, including a study by Balk et al comparing combinations of 14 clinical parameters and lab tests routinely used by clinicians in suspected sepsis patients versus SeptiCyte RAPID, which demonstrated superiority over other tests under Sepsis-2 and Sepsis-3 frameworks.
Newer host response tests are employed to identify the risk of sepsis as a screening tool, but they are exclusively for use in the ED and have low specificity and positive predictive value for sepsis. Since these tests use a technology to assess cell morphology, the results may be impacted in patients on certain therapies or patients who are immunocompromised or neutropenic. In contrast, SeptiCyte RAPID utilizes a robust gene expression signature specific to sepsis even in those challenging patient types.
Other tests, which are also used in the ED, attempt to determine if the patient has a bacterial or viral infection, along with its severity. These tests are not specifically looking to differentiate sepsis from non-infectious causes of an inflammatory response, potentially the greatest clinical challenge in diagnosing sepsis and a core strength of SeptiCyte RAPID.
Q: Do you think there will ever be a gold standard test that is specific, sensitive, and fast enough to use in every setting, or will we have an array of tests?
It is interesting to draw parallels with cancer where there is no gold standard test that confirms all cancers. Rather, there are specific tests for specific cancers and treatment regimens tailored to the cancer detected and its stage. Similarly, clinicians now recognize that sepsis is highly heterogeneous, with different phenotypes. Sepsis can present with different clinical manifestations and consequently various clinical courses, which has important implications for identification, treatment, and prognosis.
Researchers can now envisage personalized treatment approaches for sepsis to achieve optimal outcomes. This tailored sepsis treatment regimen will be dependent upon rapidly and correctly identifying sepsis and selecting the treatment option that best matches the patient-specific phenotype.
In the absence of a true gold standard, clinicians will continue to make a clinical assessment of sepsis, but the range of tools available will be more powerful. This includes AI algorithms that detect potential sepsis; screening or risk assessment tests based on cell morphology; and more accurate transcriptomic, proteomic, or metabolomic tests that differentiate sepsis from non-infectious systemic inflammation. Determining bacterial or viral sepsis and patient-specific endotype will allow for a personalized therapeutic regimen in confirmed cases of sepsis.
Q: Speed is of the essence when diagnosing sepsis. What have been some of the barriers slowing diagnostic speed and accuracy? How does SeptiCyte overcome these barriers?
One of the critical historical barriers to fast and accurate sepsis diagnosis is the length of time it takes to analyze a blood culture drawn from a suspected sepsis patient, which can be 12 to 24 hours. Over 90% of all blood cultures taken are negative, and only around half of patients retrospectively diagnosed with sepsis have positive blood culture results.
These are barriers that SeptiCyte RAPID can overcome with a one-hour turnaround time and actionable results for every patient sample tested. Recent data from three studies across three continents and 643 patients showed SeptiCyte RAPID had excellent correlation with sepsis blood culture positive patients, and samples with a SeptiScore of 11.0 had 100% specificity for a clinical diagnosis of sepsis. It should be noted that some of the barriers to diagnostic speed and accuracy have more to do with the hospital’s internal systems and protocols, such as delays in triaging the suspected sepsis patient and completing the sepsis bundle.
Q: What’s next for Immunexpress?
Our near-term goal is to achieve global regulatory clearances to use SeptiCyte RAPID in pediatric patients. We are also developing a SeptiCyte RAPID B/V test, which can determine if the sepsis identified is of bacterial or viral origin, which is critically important to inform subsequent treatment protocols.
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