Validation of SeptiCyte RAPID to Discriminate Sepsis from Non-Infectious Systemic Inflammation

Robert Balk; Annette M Esper; Greg S Martin; 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; Jared A Greenberg; Mark Yoder; Gourang Patel; Emily Gilbert; Jorge P Parada; Majid Afshar; Jordan A Kempker; Tom van der Poll; Marcus J Schultz; Brendon P Scicluna; Peter M C Klein Klouwenberg; Janice Liebler; Emily Blodget; Santhi Kumar; Krupa Navalkar; Thomas D Yager; Dayle Sampson; James T Kirk; Silvia Cermelli; Roy F Davis; Richard B Brandon

doi:10.3390/jcm13051194

Validation of SeptiCyte RAPID to Discriminate Sepsis from Non-Infectious Systemic Inflammation

J Clin Med. 2024 Feb 20;13(5):1194. doi: 10.3390/jcm13051194.

Authors

Robert Balk¹, Annette M Esper², Greg S Martin², Russell R Miller 3rd³, Bert K Lopansri^{4

5}, John P Burke^{4

5}, Mitchell Levy⁶, Steven Opal⁶, Richard E Rothman⁷, Franco R D'Alessio⁷, Venkataramana K Sidhaye⁷, Neil R Aggarwal⁸, Jared A Greenberg¹, Mark Yoder¹, Gourang Patel¹, Emily Gilbert⁹, Jorge P Parada⁹, Majid Afshar¹⁰, Jordan A Kempker², Tom van der Poll¹¹, Marcus J Schultz¹¹, Brendon P Scicluna^{12

13}, Peter M C Klein Klouwenberg¹⁴, Janice Liebler^{15

16}, Emily Blodget^{15

16}, Santhi Kumar^{15

16}, Krupa Navalkar¹⁷, Thomas D Yager¹⁷, Dayle Sampson¹⁷, James T Kirk¹⁷, Silvia Cermelli¹⁷, Roy F Davis¹⁷, Richard B Brandon¹⁷

Affiliations

¹ Rush Medical College and Rush University Medical Center, Chicago, IL 60612, USA.
² Grady Memorial Hospital and Emory University School of Medicine, Atlanta, GA 30322, USA.
³ FirstHealth of the Carolinas, Pinehurst, NC 28374, USA.
⁴ Intermountain Medical Center, Murray, UT 84107, USA.
⁵ School of Medicine, University of Utah, Salt Lake City, UT 84132, USA.
⁶ Warren Alpert Medical School, Brown University, Providence, RI 02912, USA.
⁷ School of Medicine, Johns Hopkins University, Baltimore, MD 21205, USA.
⁸ Anschutz Medical Campus, University of Colorado, Denver, CO 80045, USA.
⁹ Loyola University Medical Center, Maywood, IL 60153, USA.
¹⁰ School of Medicine and Public Health, University of Wisconsin, Madison, WI 53705, USA.
¹¹ Amsterdam UMC, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands.
¹² Centre for Molecular Medicine and Biobanking, University of Malta, Msida MSD 2080, Malta.
¹³ Department of Applied Biomedical Science, Faculty of Health Sciences, Mater Dei Hospital, University of Malta, Msida MSD 2080, Malta.
¹⁴ Fundashon Mariadal, Kralendijk, Bonaire, Netherlands Antilles.
¹⁵ Keck Hospital of University of Southern California (USC), Los Angeles, CA 90033, USA.
¹⁶ Los Angeles General Medical Center, Los Angeles, CA 90033, USA.
¹⁷ Immunexpress Inc., Seattle, DC 98109, USA.

Abstract

(1) Background: SeptiCyte RAPID is a molecular test for discriminating sepsis from non-infectious systemic inflammation, and for estimating sepsis probabilities. The objective of this study was the clinical validation of SeptiCyte RAPID, based on testing retrospectively banked and prospectively collected patient samples. (2) Methods: The cartridge-based SeptiCyte RAPID test accepts a PAXgene blood RNA sample and provides sample-to-answer processing in ~1 h. The test output (SeptiScore, range 0-15) falls into four interpretation bands, with higher scores indicating higher probabilities of sepsis. Retrospective (N = 356) and prospective (N = 63) samples were tested from adult patients in ICU who either had the systemic inflammatory response syndrome (SIRS), or were suspected of having/diagnosed with sepsis. Patients were clinically evaluated by a panel of three expert physicians blinded to the SeptiCyte test results. Results were interpreted under either the Sepsis-2 or Sepsis-3 framework. (3) Results: Under the Sepsis-2 framework, SeptiCyte RAPID performance for the combined retrospective and prospective cohorts had Areas Under the ROC Curve (AUCs) ranging from 0.82 to 0.85, a negative predictive value of 0.91 (sensitivity 0.94) for SeptiScore Band 1 (score range 0.1-5.0; lowest risk of sepsis), and a positive predictive value of 0.81 (specificity 0.90) for SeptiScore Band 4 (score range 7.4-15; highest risk of sepsis). Performance estimates for the prospective cohort ranged from AUC 0.86-0.95. For physician-adjudicated sepsis cases that were blood culture (+) or blood, urine culture (+)(+), 43/48 (90%) of SeptiCyte scores fell in Bands 3 or 4. In multivariable analysis with up to 14 additional clinical variables, SeptiScore was the most important variable for sepsis diagnosis. A comparable performance was obtained for the majority of patients reanalyzed under the Sepsis-3 definition, although a subgroup of 16 patients was identified that was called septic under Sepsis-2 but not under Sepsis-3. (4) Conclusions: This study validates SeptiCyte RAPID for estimating sepsis probability, under both the Sepsis-2 and Sepsis-3 frameworks, for hospitalized patients on their first day of ICU admission.

Keywords: SIRS; diagnosis; host response; sepsis; sepsis scoring systems.

Grants and funding

no grant number available/Immunexpress, Inc.