Validation of a Host Response Assay, SeptiCyte LAB, for Discriminating Sepsis from Systemic Inflammatory Response Syndrome in the ICU.

Abstract

RATIONALE:

A molecular test to distinguish between sepsis and systemic inflammation of noninfectious etiology could potentially have clinical utility.

OBJECTIVES:

This study evaluated the diagnostic performance of a molecular host response assay (SeptiCyte LAB) designed to distinguish between sepsis and noninfectious systemic inflammation in critically ill adults.

METHODS:

The study employed a prospective, observational, noninterventional design and recruited a heterogeneous cohort of adult critical care patients from seven sites in the United States (n = 249). An additional group of 198 patients, recruited in the large MARS (Molecular Diagnosis and Risk Stratification of Sepsis) consortium trial in the Netherlands ( www.clinicaltrials.gov identifier NCT01905033), was also tested and analyzed, making a grand total of 447 patients in our study. The performance of SeptiCyte LAB was compared with retrospective physician diagnosis by a panel of three experts.

MEASUREMENTS AND MAIN RESULTS:

In receiver operating characteristic curve analysis, SeptiCyte LAB had an estimated area under the curve of 0.82-0.89 for discriminating sepsis from noninfectious systemic inflammation. The relative likelihood of sepsis versus noninfectious systemic inflammation was found to increase with increasing test score (range, 0-10). In a forward logistic regression analysis, the diagnostic performance of the assay was improved only marginally when used in combination with other clinical and laboratory variables, including procalcitonin. The performance of the assay was not significantly affected by demographic variables, including age, sex, or race/ethnicity.

CONCLUSIONS:

SeptiCyte LAB appears to be a promising diagnostic tool to complement physician assessment of infection likelihood in critically ill adult patients with systemic inflammation. Clinical trial registered with www.clinicaltrials.gov (NCT01905033 and NCT02127502).

• Authors: Russell R Miller 3rd, Bert K Lopansri, John P Burke, Mitchell Levy, Steven Opal, Richard E Rothman, Franco R D'Alessio, Venkataramana K Sidhaye, Neil R Aggarwal, Robert Balk, Jared A Greenberg, Mark Yoder, Gourang Patel, Emily Gilbert, Majid Afshar, Jorge P Parada, Greg S Martin, Annette M Esper, Jordan A Kempker, Mangala Narasimhan, Adey Tsegaye, Stella Hahn, Paul Mayo, Tom van der Poll, Marcus J Schultz, Brendon P Scicluna, Peter Klein Klouwenberg, Antony Rapisarda, Therese A Seldon, Leo C McHugh, Thomas D Yager, Silvia Cermelli, Dayle Sampson, Victoria Rothwell, Richard Newman, Shruti Bhide, Brian A Fox, James T Kirk, Krupa Navalkar, Roy F Davis, Roslyn A Brandon, Richard B Brandon
• Journal: American journal of respiratory and critical care medicine (Am J Respir Crit Care Med) Vol. 198 Issue 7 Pg. 903-913 (10 01 2018) ISSN: 1535-4970 [Electronic] United States
• PMID: 29624409 (Publication Type: Journal Article, Multicenter Study, Observational Study, Research Support, Non-U.S. Gov't, Validation Study)

Topics

• Adult
• Aged
• Cohort Studies
• Critical Care (methods)
• Critical Illness
• Diagnosis, Differential
• Female
• Humans
• Intensive Care Units
• Male
• Middle Aged
• Netherlands
• Prospective Studies
• ROC Curve
• Retrospective Studies
• Sensitivity and Specificity
• Sepsis (blood, diagnosis)
• Serum Bactericidal Test (methods)
• Systemic Inflammatory Response Syndrome (blood, diagnosis)
• United States