NEW YORK (360Dx) – A recently cleared blood-based test from Beckman Coulter could hasten better and more appropriate treatment of sepsis patients, according to the company.
The Early Sepsis Indicator test from Beckman Coulter was cleared by the US Food and Drug Administration in March for the routine screening of early signs of sepsis in patients entering the emergency department. The test was cleared for use on Beckman Coulter's DxH 900 hematology analyzer for marketing to US hospitals after it received CE marking for marketing in Europe last year.
Based on a hematology cellular biomarker, it identifies morphological changes within monocyte white blood cells, and could enable more appropriate and faster treatments for sepsis patients, Jeannine Holden, vice president of medical and scientific affairs and chief medical officer at Beckman Coulter, the test developer, said last week on the sidelines of the European Congress of Clinical Microbiology & Infectious Diseases (ECCMID) in Amsterdam.
Clinicians have already used this type of analyzer to calculate white blood cell count with differential, which determines the percentage of each type of white blood cell in the blood, to assess the health of patients entering the emergency department. Using the new analyzer, they can get test results in about one hour, according to Beckman Coulter.
"It's called the Early Sepsis Indicator not just because we're looking at something that happens early in the sepsis process but because it happens so early in the emergency care pathway," Holden said.
The sepsis indicator is based on a monocyte-distribution-width (MDW) biomarker, which clinicians can use to discriminate sepsis from similar conditions when they combine the marker with the current standard-of-care, which is a combination of standard clinical measurements, Holden said.
Hematology analyzers already measure the volume of neutrophils — white blood cells that are part of the innate immune system and that increase in response to infections, providing a warning that the patient could have sepsis as well as other similar conditions, Holden said.
Beckman Coulter and its clinical investigators decided to investigate the behavior of monocyte white blood cells that are also part of the innate immune system. "It turned out that monocyte volumes change as they undergo immunophenotypic changes," Holden said, adding that those functional and immunophenotypic changes are reflective of their being associated with sepsis.
To produce a monocyte distribution width measurement, the instrument performs a statistical analysis associated with the distribution of cell sizes.
Clinicians can connect the indicator, which only works on Beckman Coulter analyzers, with the firm's Remisol Advance middleware, which itself connects laboratory information systems and the results of instrumentation that spans multiple disciplines, including hematology, clinical chemistry, immunoassay, microbiology, and urinalysis, Holden said. That's important, she noted, because clinicians' analyses can benefit from being able to combine results of the early sepsis indicator with information from other tests and clinical inputs.
Being able to identify sepsis so quickly should prove vital for care of patients whose health can deteriorate rapidly and who can experience organ shut down, loss of limbs, and death if they are not quickly given an appropriate treatment.
Currently, patients suspected of having sepsis or a similar condition upon entering the ED often undergo a clinical evaluation involving measurement of their rate of breathing, temperature, heart rate, and white blood cell count. If clinicians suspect that sepsis is present, they apply a sepsis bundle that includes administering a broad spectrum antibiotic.
Despite the use and availability of early clinical parameters, sepsis is still difficult to properly diagnose, and patients can frequently have systemic inflammatory response syndrome (SIRS), a condition that might involve sepsis or might not, Elliott Crouser, principal investigator in the pivotal clinical trial for the Early Sepsis Indicator and a physician in the intensive care unit at the Ohio State University Wexner Medical Center, said in an interview. When SIRS is not accompanied by sepsis, clinicians need to administer a different treatment.
Additionally, the clinician must also decide whether an infection specific to one part of the body has become severe and systemic, and certain parts of the patient population, such as young adults, are particularly difficult to diagnose, Holden noted.
In clinical studies, the time to treatment from admission in the emergency department to administration of treatment for sepsis was delayed by an average of four hours when clinicians were applying standard of care testing and treatment, Crouser said.
With the Early Sepsis Indicator, "ideally, we want to get the time to detect sepsis down to less than two hours," he said.
In the clinical trial led by Crouser, 2,158 patients were enrolled from April 2017 through January 2018. Test results from the University of Pittsburgh Medical Center and Hackensack University Medical Center were also included, and findings from the trial are expected to be be published soon in the journal Critical Care Medicine, Crouser said.
According to Beckman Coulter, a positive result in the trial signaled a higher probability of sepsis and enabled physicians to initiate lifesaving treatments faster, and a negative reading indicated a lower probability of sepsis. Compared to reviewing white blood cell count alone, the sepsis indicator strengthens a clinician’s suspicion of sepsis by 43 percent. When the results are combined with clinical signs and symptoms, a clinician's confidence in helping to rule out sepsis improves by 63 percent, the firm said.
Crouser noted that the FDA clearance is for use of the Early Sepsis Indicator with adults in the ED "because that was the clinical setting used in the clinical trial."
Holden noted that clinicians would use the Early Sepsis Indicator prior to performing other tests to confirm or rule out sepsis, including procalcitonin biomarkers, molecular tests, and antimicrobial susceptibility tests.
Many diagnostic companies already market procalcitonin and molecular tests to diagnose bloodstream infections, including sepsis. Beckman Coulter itself has developed a new procalcitonin immunoassay that has received CE marking and is pending an FDA decision for clearance in the US, Holden said.
In April, GenMark Diagnostics received 510(k) clearance from the US Food and Drug Administration for a panel to detect gram-negative bacteria in blood cultures. It completes GenMark's suite of multiplex panels to detect bloodstream infections that can cause sepsis.
French diagnostics firm Novacyt said recently that its molecular testing division Primerdesign has extended its sepsis assay development contract with Immunexpress.
In February, Immunexpress said it received a funding commitment of $744,739 from the US Department of Health and Human Services (HHS) for the development and commercialization of its SeptiCyte sample-to-result sepsis assay.