Sepsis versus SIRS blood test shows high sensitivity

A molecular host response assay, called SeptiCyte Lab, holds promise as a tool to distinguish between sepsis and noninfectious systemic inflammation (SIRS), reported researchers in an industry-funded study.

Sepsis is a complex and hard-to-diagnose condition, noted two members of the editorial advisory board of CHEST Physician^® in interviews. To make things more complicated, there’s not even a standard definition of sepsis, explained board member Nirmal S. Sharma, MD, of the University of South Florida, Tampa.

“Although newer sepsis definitions have been proposed, all of them have pitfalls and are not used universally. Additionally, the presence of inflammatory response leading to suspicion of sepsis can be due to a new infection or underlying disease processes, thus making it difficult to identify the possible cause,” said Dr. Sharma. “Culture-negative cases due to the use of antibiotics prior to suspicion/onset of sepsis can further muddle the picture. Finally, in certain subsets of patients, such as the immunocompromised and elderly, the signs of sepsis may be delayed due to inadequate/dampened immune response, thus making early diagnosis difficult.”

Blood testing can provide information about germs that are causing an infection, but “they often take several days, and we need to start the antibiotics before we have those results,” added Daniel R. Ouellette, MD, FCCP, the other board member interviewed.

The SeptiCyte Lab assay, which was approved by the FDA for use in diagnosing sepsis in 2017, was developed to help physicians distinguish sepsis from SIRS in patients during their first day of ICU treatment, noted the authors of the new study in the American Journal of Respiratory and Critical Care Medicine.

This new tool seems to overcome some of the obstacles encountered when other diagnostic methods are used to determine if a patient has sepsis.

Russell R. Miller III, MD, FCCM, and his colleagues performed their SeptiCyte Lab assay on patients’ blood samples; this involved real-time, reverse-transcription, quantitative polymerase chain reaction screening designed to analyze the relative expression levels of four genes. The testing procedure took approximately 6 hours from the draw of the blood sample, according to the study, which was recently published online.

The predictive sensitivity of the test was 0.97 in patients unanimously considered to have sepsis by expert panels comprising three members. Negative predictive values were at least 0.89, according to the researchers.

Overall, the findings show “good reliability,” wrote Dr. Miller of the Intermountain Medical Center in Murray, Utah, and the University of Utah, Salt Lake City, and his colleagues.

The test produced scores in four bands, with scores at or above 3.1 considered to be evidence of infection. Lower levels were considered to be evidence of noninfection.

Dr. Miller and his coauthors reported that 86% of patients unanimously considered to have sepsis had scores above 3.1. In contrast, only 30% of those considered to have SIRS had such high scores.

In addition, the study authors determined that the test was more reliable than were the clinical signs and laboratory variables that are commonly used to diagnose sepsis within 24 hours of arrival at the ICU.

Reaching a definitive sepsis diagnosis is challenging based on clinical signs alone, since various conditions mimic the signs of sepsis, noted Dr. Ouellette of Henry Ford Hospital and Wayne State University School of Medicine in Detroit.

In some cases, physicians simply assume that a patient has sepsis and begin antibiotics, he said, “but that’s not a free ride. Each [antibiotic] may produce side effects with consequences for patients. The other problem is that overuse of antibiotics leads to resistance.”

The study by Dr. Miller and his colleagues combined the results of three trials conducted from during 2011-2016 in the United States and the Netherlands in 447 subjects.

One trial analyzed the experiences of 198 consecutive subjects, all critically ill, who met various criteria. (They were part of a consortium trial of 7,500 patients). The second trial had 129 participants, and the third had 120. Of the total participants, 71% were white and 20% were black.

Inclusion of procalcitonin levels in the laboratory variables didn’t appear to make a significant difference. The study authors wrote that the test “differs from, and is complementary to that of procalcitonin. The latter test is cleared for predicting progression from severe sepsis to septic shock, for predicting 28-day mortality, and for managing antibiotic de-escalation.”

According to the researchers, differences in age, sex, and race/ethnicity did not significantly affect the test.

The study concludes by noting that “future studies are warranted to determine how host gene expression could most effectively be integrated into clinical decision making to ensure susceptible patients are accurately managed early in the course of disease.”

The test is “promising new technology, but I don’t think you could say it’s definitive,” noted Dr. Ouellette.“Like any test, it’s not perfect,” he explained. “That’s important because physicians wouldn’t want to guess wrong. We might err on the side of choosing to treat with antibiotics even in the face of a test that suggested they might not have infection.”

Immunexpress and the Australian Government funded the study. Fourteen authors disclosed being current or former employees of Immunexpress and/or shareholders; others reported receiving funding from the company via their institutions. Four authors declared having filed patent applications related to the study or to the diagnosis of community-acquired pneumonia upon ICU admission. Some authors reported various other disclosures.

Dr. Ouellette and Dr. Sharma said they did not have any disclosures.

SOURCE: Miller RR et al. Am J Respir Crit Care Med. 2018 Apr 6. doi: 10.1164/rccm.201712-2472OC.

A molecular host response assay, called SeptiCyte Lab, holds promise as a tool to distinguish between sepsis and noninfectious systemic inflammation (SIRS), reported researchers in an industry-funded study.

Sepsis is a complex and hard-to-diagnose condition, noted two members of the editorial advisory board of CHEST Physician^® in interviews. To make things more complicated, there’s not even a standard definition of sepsis, explained board member Nirmal S. Sharma, MD, of the University of South Florida, Tampa.

“Although newer sepsis definitions have been proposed, all of them have pitfalls and are not used universally. Additionally, the presence of inflammatory response leading to suspicion of sepsis can be due to a new infection or underlying disease processes, thus making it difficult to identify the possible cause,” said Dr. Sharma. “Culture-negative cases due to the use of antibiotics prior to suspicion/onset of sepsis can further muddle the picture. Finally, in certain subsets of patients, such as the immunocompromised and elderly, the signs of sepsis may be delayed due to inadequate/dampened immune response, thus making early diagnosis difficult.”

Blood testing can provide information about germs that are causing an infection, but “they often take several days, and we need to start the antibiotics before we have those results,” added Daniel R. Ouellette, MD, FCCP, the other board member interviewed.

The SeptiCyte Lab assay, which was approved by the FDA for use in diagnosing sepsis in 2017, was developed to help physicians distinguish sepsis from SIRS in patients during their first day of ICU treatment, noted the authors of the new study in the American Journal of Respiratory and Critical Care Medicine.

This new tool seems to overcome some of the obstacles encountered when other diagnostic methods are used to determine if a patient has sepsis.

Russell R. Miller III, MD, FCCM, and his colleagues performed their SeptiCyte Lab assay on patients’ blood samples; this involved real-time, reverse-transcription, quantitative polymerase chain reaction screening designed to analyze the relative expression levels of four genes. The testing procedure took approximately 6 hours from the draw of the blood sample, according to the study, which was recently published online.

The predictive sensitivity of the test was 0.97 in patients unanimously considered to have sepsis by expert panels comprising three members. Negative predictive values were at least 0.89, according to the researchers.

Overall, the findings show “good reliability,” wrote Dr. Miller of the Intermountain Medical Center in Murray, Utah, and the University of Utah, Salt Lake City, and his colleagues.

The test produced scores in four bands, with scores at or above 3.1 considered to be evidence of infection. Lower levels were considered to be evidence of noninfection.

Dr. Miller and his coauthors reported that 86% of patients unanimously considered to have sepsis had scores above 3.1. In contrast, only 30% of those considered to have SIRS had such high scores.

In addition, the study authors determined that the test was more reliable than were the clinical signs and laboratory variables that are commonly used to diagnose sepsis within 24 hours of arrival at the ICU.

Reaching a definitive sepsis diagnosis is challenging based on clinical signs alone, since various conditions mimic the signs of sepsis, noted Dr. Ouellette of Henry Ford Hospital and Wayne State University School of Medicine in Detroit.

In some cases, physicians simply assume that a patient has sepsis and begin antibiotics, he said, “but that’s not a free ride. Each [antibiotic] may produce side effects with consequences for patients. The other problem is that overuse of antibiotics leads to resistance.”

The study by Dr. Miller and his colleagues combined the results of three trials conducted from during 2011-2016 in the United States and the Netherlands in 447 subjects.

One trial analyzed the experiences of 198 consecutive subjects, all critically ill, who met various criteria. (They were part of a consortium trial of 7,500 patients). The second trial had 129 participants, and the third had 120. Of the total participants, 71% were white and 20% were black.

Inclusion of procalcitonin levels in the laboratory variables didn’t appear to make a significant difference. The study authors wrote that the test “differs from, and is complementary to that of procalcitonin. The latter test is cleared for predicting progression from severe sepsis to septic shock, for predicting 28-day mortality, and for managing antibiotic de-escalation.”

According to the researchers, differences in age, sex, and race/ethnicity did not significantly affect the test.

The study concludes by noting that “future studies are warranted to determine how host gene expression could most effectively be integrated into clinical decision making to ensure susceptible patients are accurately managed early in the course of disease.”

The test is “promising new technology, but I don’t think you could say it’s definitive,” noted Dr. Ouellette.“Like any test, it’s not perfect,” he explained. “That’s important because physicians wouldn’t want to guess wrong. We might err on the side of choosing to treat with antibiotics even in the face of a test that suggested they might not have infection.”

Immunexpress and the Australian Government funded the study. Fourteen authors disclosed being current or former employees of Immunexpress and/or shareholders; others reported receiving funding from the company via their institutions. Four authors declared having filed patent applications related to the study or to the diagnosis of community-acquired pneumonia upon ICU admission. Some authors reported various other disclosures.

Dr. Ouellette and Dr. Sharma said they did not have any disclosures.

SOURCE: Miller RR et al. Am J Respir Crit Care Med. 2018 Apr 6. doi: 10.1164/rccm.201712-2472OC.

A molecular host response assay, called SeptiCyte Lab, holds promise as a tool to distinguish between sepsis and noninfectious systemic inflammation (SIRS), reported researchers in an industry-funded study.

Sepsis is a complex and hard-to-diagnose condition, noted two members of the editorial advisory board of CHEST Physician^® in interviews. To make things more complicated, there’s not even a standard definition of sepsis, explained board member Nirmal S. Sharma, MD, of the University of South Florida, Tampa.

“Although newer sepsis definitions have been proposed, all of them have pitfalls and are not used universally. Additionally, the presence of inflammatory response leading to suspicion of sepsis can be due to a new infection or underlying disease processes, thus making it difficult to identify the possible cause,” said Dr. Sharma. “Culture-negative cases due to the use of antibiotics prior to suspicion/onset of sepsis can further muddle the picture. Finally, in certain subsets of patients, such as the immunocompromised and elderly, the signs of sepsis may be delayed due to inadequate/dampened immune response, thus making early diagnosis difficult.”

Blood testing can provide information about germs that are causing an infection, but “they often take several days, and we need to start the antibiotics before we have those results,” added Daniel R. Ouellette, MD, FCCP, the other board member interviewed.

The SeptiCyte Lab assay, which was approved by the FDA for use in diagnosing sepsis in 2017, was developed to help physicians distinguish sepsis from SIRS in patients during their first day of ICU treatment, noted the authors of the new study in the American Journal of Respiratory and Critical Care Medicine.

This new tool seems to overcome some of the obstacles encountered when other diagnostic methods are used to determine if a patient has sepsis.

Russell R. Miller III, MD, FCCM, and his colleagues performed their SeptiCyte Lab assay on patients’ blood samples; this involved real-time, reverse-transcription, quantitative polymerase chain reaction screening designed to analyze the relative expression levels of four genes. The testing procedure took approximately 6 hours from the draw of the blood sample, according to the study, which was recently published online.

The predictive sensitivity of the test was 0.97 in patients unanimously considered to have sepsis by expert panels comprising three members. Negative predictive values were at least 0.89, according to the researchers.

Overall, the findings show “good reliability,” wrote Dr. Miller of the Intermountain Medical Center in Murray, Utah, and the University of Utah, Salt Lake City, and his colleagues.

The test produced scores in four bands, with scores at or above 3.1 considered to be evidence of infection. Lower levels were considered to be evidence of noninfection.

Dr. Miller and his coauthors reported that 86% of patients unanimously considered to have sepsis had scores above 3.1. In contrast, only 30% of those considered to have SIRS had such high scores.

In addition, the study authors determined that the test was more reliable than were the clinical signs and laboratory variables that are commonly used to diagnose sepsis within 24 hours of arrival at the ICU.

Reaching a definitive sepsis diagnosis is challenging based on clinical signs alone, since various conditions mimic the signs of sepsis, noted Dr. Ouellette of Henry Ford Hospital and Wayne State University School of Medicine in Detroit.

In some cases, physicians simply assume that a patient has sepsis and begin antibiotics, he said, “but that’s not a free ride. Each [antibiotic] may produce side effects with consequences for patients. The other problem is that overuse of antibiotics leads to resistance.”

The study by Dr. Miller and his colleagues combined the results of three trials conducted from during 2011-2016 in the United States and the Netherlands in 447 subjects.

One trial analyzed the experiences of 198 consecutive subjects, all critically ill, who met various criteria. (They were part of a consortium trial of 7,500 patients). The second trial had 129 participants, and the third had 120. Of the total participants, 71% were white and 20% were black.

Inclusion of procalcitonin levels in the laboratory variables didn’t appear to make a significant difference. The study authors wrote that the test “differs from, and is complementary to that of procalcitonin. The latter test is cleared for predicting progression from severe sepsis to septic shock, for predicting 28-day mortality, and for managing antibiotic de-escalation.”

According to the researchers, differences in age, sex, and race/ethnicity did not significantly affect the test.

The study concludes by noting that “future studies are warranted to determine how host gene expression could most effectively be integrated into clinical decision making to ensure susceptible patients are accurately managed early in the course of disease.”

The test is “promising new technology, but I don’t think you could say it’s definitive,” noted Dr. Ouellette.“Like any test, it’s not perfect,” he explained. “That’s important because physicians wouldn’t want to guess wrong. We might err on the side of choosing to treat with antibiotics even in the face of a test that suggested they might not have infection.”

Immunexpress and the Australian Government funded the study. Fourteen authors disclosed being current or former employees of Immunexpress and/or shareholders; others reported receiving funding from the company via their institutions. Four authors declared having filed patent applications related to the study or to the diagnosis of community-acquired pneumonia upon ICU admission. Some authors reported various other disclosures.

Dr. Ouellette and Dr. Sharma said they did not have any disclosures.

SOURCE: Miller RR et al. Am J Respir Crit Care Med. 2018 Apr 6. doi: 10.1164/rccm.201712-2472OC.