{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T05:16:12Z","timestamp":1788412572858,"version":"build-2803163510"},"reference-count":45,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T00:00:00Z","timestamp":1788220800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100020249","name":"Immunexpress Inc.","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100020249","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Diseases"],"abstract":"<jats:p>Background: Accurate early identification of sepsis remains a major clinical challenge due to its heterogeneous presentation and overlap of clinical signs with the non-infectious systemic inflammatory response syndrome (SIRS). Timely differentiation is crucial for improving patient outcomes, meeting sepsis bundle requirements and reducing inappropriate antimicrobial use. We hypothesized that clinical\u2013laboratory data available within the first three hours of patient presentation could be used to identify patients with sepsis at a clinically useful level of diagnostic accuracy, in lieu of traditional microbiology results which would not become available until at least 12\u201324 h. Data from two independent studies were used to quantify the diagnostic value of demographic, vital, clinical\u2013laboratory, and microbiological data available at three time points for distinguishing retrospectively diagnosed critically ill patients with either sepsis or non-infectious SIRS. A particular focus of this work was an assessment of the utility of SeptiCyte RAPID (Immunexpress Inc., Seattle, WA, USA) as an aid to sepsis diagnosis, producing actionable data within one hour. Methods: Data from two independent study cohorts were analyzed. The \u201c510(k) cohort\u201d consisted of 419 adult patients in intensive care (ICU) (MARS, VENUS, and NEPTUNE studies). The \u201cAndalusian cohort\u201d consisted of 353 ICU patients from the PANGEA study. Logistic regression models, selected by a greedy search algorithm and validated by repeated cross-validation, were used to determine the contributions of different variables to diagnostic accuracy. Diagnostic performance was quantified by the area under the receiver operating characteristic curve (AUC). Results: For the 510(k) cohort, a baseline AUC of 0.69\u20130.73 was observed using five to seven vital and demographic variables assessed immediately upon presentation (time T1). The addition of clinical\u2013laboratory variables, in particular SeptiCyte RAPID, within one to three hours post-presentation (time T2) increased the AUC to 0.85\u20130.86. Finally, the addition of microbiological data 12\u201324 h post-presentation (time T3) further improved the AUC to 0.90\u20130.91. Similar results were obtained for the Andalusian cohort. AUC values at the three time points were as follows: At time T1, AUC = 0.67 based solely on vital signs and demographics; at time T2, AUC = 0.87 based on vitals + demographics + SeptiCyte RAPID \u00b1 other clinical\u2013laboratory data; at time T3, AUC = 0.93 based on vitals + demographics + SeptiCyte RAPID \u00b1 other clinical\u2013laboratory data + microbiology results. For both cohorts, the most significant variables included temperature, mean arterial pressure, respiratory rate, suspected infection site, SeptiCyte RAPID, procalcitonin, confirmed bacterial infection and positive blood culture confirmation. In summary, the AUC for diagnosing sepsis rose progressively from T1 (510(k) 0.69\u20130.73; Andalusian 0.67) to T2 (510(k) 0.85\u20130.86; Andalusian 0.87) with the addition of SeptiCyte RAPID to T3 (510(k) 0.90\u20130.91; Andalusian 0.93) as more clinical information became available over time. Conclusions: The accuracy of identification of sepsis increases markedly as demographics and vital signs are supplemented with clinical\u2013laboratory information, and ultimately with microbiological culture results. The AUC improves in the shortest time within the first three hours when laboratory data, and particularly SeptiCyte RAPID results, become available. Integrating rapid host response testing with SeptiCyte RAPID into time-based diagnostic frameworks may enhance early sepsis recognition, improve antimicrobial stewardship, and support guideline-driven clinical decisions.<\/jats:p>","DOI":"10.3390\/diseases14090319","type":"journal-article","created":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T09:48:36Z","timestamp":1788256116000},"page":"319","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Sequential Application of Time-Stratified Demographic, Vital, Clinical\u2013Laboratory, and Microbiology Variables for Accurate and Rapid Identification of Sepsis"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4751-6130","authenticated-orcid":false,"given":"Krupa Arun","family":"Navalkar","sequence":"first","affiliation":[{"name":"Immunexpress Inc., Seattle, WA 98109, USA"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"visualization","vocabulary":"credit"},{"role":"software","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2542-7601","authenticated-orcid":false,"given":"Jos\u00e9","family":"Garnacho-Montero","sequence":"additional","affiliation":[{"name":"Intensive Care Unit, Hospital Universitario Virgen del Roc\u00edo, 41013 Sevilla, Spain"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"funding-acquisition","vocabulary":"credit"},{"role":"project-administration","vocabulary":"credit"},{"role":"validation","vocabulary":"credit"},{"role":"supervision","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1024-2954","authenticated-orcid":false,"given":"Mar\u00eda Luisa","family":"Cant\u00f3n-Bulnes","sequence":"additional","affiliation":[{"name":"Intensive Care Unit, Hospital Universitario Virgen Macarena, 41009 Sevilla, Spain"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"funding-acquisition","vocabulary":"credit"},{"role":"project-administration","vocabulary":"credit"},{"role":"supervision","vocabulary":"credit"},{"role":"validation","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1443-9236","authenticated-orcid":false,"given":"Jos\u00e9 Lu\u00eds","family":"Garc\u00eda-Garmendia","sequence":"additional","affiliation":[{"name":"Intensive Care Unit, Hospital San Juan de Dios del Aljarafe, 41930 Sevilla, Spain"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"validation","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0665-557X","authenticated-orcid":false,"given":"\u00c1ngel","family":"Estella","sequence":"additional","affiliation":[{"name":"Intensive Care Unit, Hospital Universitario de Jerez de la Frontera, 11407 C\u00e1diz, Spain"},{"name":"Instituto de Investigaci\u00f3n e Innovaci\u00f3n Biom\u00e9dica de C\u00e1diz (INiBICA), Department of Medicine and Surgery, University of C\u00e1diz, 11003 C\u00e1diz, Spain"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"validation","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4859-3293","authenticated-orcid":false,"given":"Adela","family":"Fern\u00e1ndez-Galilea","sequence":"additional","affiliation":[{"name":"Intensive Care Unit, Hospital Universitario Virgen del Roc\u00edo, 41013 Sevilla, 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Engl. J. Med."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1041","DOI":"10.1007\/s15010-023-02158-w","article-title":"Sepsis mimics among presumed sepsis patients at intensive care admission: A retrospective observational study","volume":"52","author":"Lengquist","year":"2024","journal-title":"Infection"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"725","DOI":"10.1097\/CCM.0000000000007089","article-title":"Surviving Sepsis Campaign: International guidelines for management of sepsis and septic shock 2026","volume":"54","author":"Prescott","year":"2026","journal-title":"Crit. Care Med."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"202","DOI":"10.1186\/s13054-019-2475-9","article-title":"In-hospital mortality associated with the misdiagnosis or unidentified site of infection at admission","volume":"23","author":"Abe","year":"2019","journal-title":"Crit. Care"},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"La Russa, R., Viola, R.V., D\u2019Errico, S., Aromatario, M., Maiese, A., Anibaldi, P., Napoli, C., Frati, P., and Fineschi, V. (2021). Analysis of Inadequacies in Hospital Care through Medical Liability Litigation. Int. J. Environ. Res. Public Health, 18.","DOI":"10.3390\/ijerph18073425"},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Liu, P., Yang, Y., and Cheng, J. (2022). Gender differences in medical errors among older patients and inequalities in medical compensation compared with younger adults. Front. Public Health, 10.","DOI":"10.3389\/fpubh.2022.883822"},{"key":"ref_7","unstructured":"(2025, March 28). OECD Health Working Papers No. 176. The Economics of Diagnostic Safety. Available online: https:\/\/www.oecd.org\/en\/publications\/the-economics-of-diagnostic-safety_fc61057a-en.html."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1515\/dx-2019-0019","article-title":"Serious misdiagnosis-related harms in malpractice claims: The \u201cBig Three\u201d\u2014Vascular events, infections, and cancers","volume":"6","author":"Schaffer","year":"2019","journal-title":"Diagnosis"},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Balk, R., Esper, A.M., Martin, G.S., Miller, R.R., Lopansri, B.K., Burke, J.P., Levy, M., Opal, S., Rothman, R.E., and D\u2019alessio, F.R. (2024). Validation of SeptiCyte RAPID to discriminate sepsis from non-infectious systemic inflammation. J. Clin. Med., 13.","DOI":"10.3390\/jcm13051194"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1605","DOI":"10.1007\/s10096-026-05431-6","article-title":"Diagnostic accuracy of SeptiCyte RAPID to discriminate sepsis from non-infectious critical illness in patients meeting sepsis criteria according to Sepsis-3 definition at ICU admission","volume":"45","author":"Estella","year":"2026","journal-title":"Eur. J. Clin. Microbiol. Infect. Dis."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"903","DOI":"10.1164\/rccm.201712-2472OC","article-title":"Validation of a Host Response Assay, SeptiCyte LAB, for Discriminating Sepsis from Systemic Inflammatory Response Syndrome in the ICU","volume":"198","author":"Miller","year":"2018","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1177\/0025817220926915","article-title":"Thromboinflammatory response in SARS-CoV-2 sepsis","volume":"88","author":"Maiese","year":"2020","journal-title":"Med. Leg. J."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1186\/s40560-019-0368-2","article-title":"Physician agreement on the diagnosis of sepsis in the intensive care unit: Estimation of concordance and analysis of underlying factors in a multicenter cohort","volume":"7","author":"Lopansri","year":"2019","journal-title":"J. Intensive Care"},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Jakobsen, J.C., Gluud, C., Wetterslev, J., and Winkel, P. (2017). When and how should multiple imputation be used for handling missing data in randomised clinical trials\u2014A practical guide with flowcharts. BMC Med. Res. Methodol., 17.","DOI":"10.1186\/s12874-017-0442-1"},{"key":"ref_15","first-page":"1","article-title":"FactoMineR: An R Package for Multivariate Analysis","volume":"25","author":"Josse","year":"2008","journal-title":"J. Stat. Softw."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1016\/S0140-6736(18)30696-2","article-title":"Sepsis and septic shock","volume":"392","author":"Cecconi","year":"2018","journal-title":"Lancet"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1186\/s40364-021-00329-1","article-title":"Multifaced roles of PLAC8 in cancer","volume":"9","author":"Mao","year":"2021","journal-title":"Biomark. Res."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"308","DOI":"10.1038\/s41420-024-02012-4","article-title":"Plac8-ERK pathway modulation of monocyte function in sepsis","volume":"10","author":"Zhang","year":"2024","journal-title":"Cell Death Discov."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1038\/s41392-022-01052-5","article-title":"PLA2G7: A new player in shaping energy metabolism and lifespan","volume":"7","author":"Candels","year":"2022","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1080\/09629350020002921","article-title":"Platelet-activating factor acetylhydrolase and haemophagocytosis in the sepsis syndrome","volume":"9","author":"Trimoreau","year":"2000","journal-title":"Mediat. Inflamm."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"2172","DOI":"10.1007\/s12094-024-03413-8","article-title":"Logistic regression and other statistical tools in diagnostic biomarker studies","volume":"26","author":"Elkahwagy","year":"2024","journal-title":"Clin. Transl. Oncol."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Robin, X., Turck, N., Hainard, A., Tiberti, N., Lisacek, F., Sanchez, J.-C., and M\u00fcller, M. (2011). pROC: An open-source package for R and S+ to analyze and compare ROC curves. BMC Bioinform., 12.","DOI":"10.1186\/1471-2105-12-77"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1364","DOI":"10.1109\/TKDE.2003.1245278","article-title":"Dimensionality Reduction in Automatic Knowledge Acquisition: A Simple Greedy Search Approach","volume":"15","author":"Huang","year":"2003","journal-title":"IEEE Trans. Knowl. Data Eng."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"837","DOI":"10.2307\/2531595","article-title":"Comparing the areas under two or more correlated receiver operating characteristic curves: A nonparametric approach","volume":"44","author":"DeLong","year":"1988","journal-title":"Biometrics"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"2577","DOI":"10.1002\/sim.5328","article-title":"Misuse of DeLong test to compare AUCs for nested models","volume":"31","author":"Demler","year":"2012","journal-title":"Stat. Med."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Hastie, T., Tibshirani, R., and Friedman, J. (2009). The Elements of Statistical Learning: Data Mining, Inference, and Prediction, Springer. [2nd ed.].","DOI":"10.1007\/978-0-387-84858-7"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"104529","DOI":"10.1016\/j.ijnurstu.2023.104529","article-title":"Evaluation of evolving sepsis screening criteria to identify sepsis","volume":"145","author":"Rincon","year":"2023","journal-title":"Int. J. Nurs. Stud."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"2441","DOI":"10.1007\/s10096-024-04961-1","article-title":"Validation of MEWS, NEWS, NEWS-2 and qSOFA for different infection foci at the emergency department, the acutelines cohort","volume":"43","author":"Postma","year":"2024","journal-title":"Eur. J. Clin. Microbiol. Infect. Dis."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1007\/s11908-021-00765-y","article-title":"Diagnostic challenges in sepsis","volume":"23","author":"Duncan","year":"2021","journal-title":"Curr. Infect. Dis. Rep."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1097\/SHK.0000000000000411","article-title":"The utility of inflammatory and endothelial markers to identify infection in emergency department patients","volume":"44","author":"Day","year":"2015","journal-title":"Shock"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"104751","DOI":"10.1016\/j.idnow.2023.104751","article-title":"Diagnostic uncertainty in infectious diseases: Advocacy for a nosological framework","volume":"53","author":"Roger","year":"2023","journal-title":"Infect. Dis. Now"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"e2138596","DOI":"10.1001\/jamanetworkopen.2021.38596","article-title":"Association between implementation of the SEP-1 bundle and outcomes in patients with suspected sepsis in US hospitals","volume":"4","author":"Rhee","year":"2021","journal-title":"JAMA Netw. Open"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"174","DOI":"10.1017\/S1481803500009891","article-title":"Incorporation bias in studies of diagnostic tests: How to avoid being biased","volume":"10","author":"Worster","year":"2008","journal-title":"Can. J. Emerg. Med."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1194","DOI":"10.1111\/acem.12255","article-title":"Understanding the direction of bias in Studies of diagnostic test accuracy","volume":"20","author":"Kohn","year":"2013","journal-title":"Acad. Emerg. Med."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1016\/j.jclinepi.2016.03.022","article-title":"Partial verification bias and incorporation bias affected accuracy estimates of diagnostic studies for biomarkers that were part of an existing composite gold standard","volume":"74","author":"Karch","year":"2016","journal-title":"J. Clin. Epidemiol."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Navalkar, K.A., Wani, P., Davis, R.F., Cermelli, S., Dietrich, M., von der Forst, M., Becker, S.L., Benthien, S., Baumann, E., and Zeiner, C. (2026). Ruling In and Ruling Out Sepsis Using Likelihood Ratios of a Host Response Assay. Diagnostics, 16.","DOI":"10.64898\/2026.05.29.26354374"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"703","DOI":"10.1001\/jama.1994.03510330081039","article-title":"Users\u2019 guides to the medical literature. III. How to use an article about a diagnostic test. B. What are the results and will they help me in caring for my patients?","volume":"271","author":"Jaeschke","year":"1994","journal-title":"JAMA"},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"McHugh, L.C., Snyder, K., and Yager, T.D. (2019). The effect of uncertainty in patient classification on diagnostic performance estimations. PLoS ONE, 14.","DOI":"10.1371\/journal.pone.0218492"},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Vincent, J.-L. (2016). The Clinical Challenge of Sepsis Identification and Monitoring. PLoS Med., 13.","DOI":"10.1371\/journal.pmed.1002022"},{"key":"ref_40","unstructured":"Bion, J., Barton, G., Boyle, A., Carlson, G., Carrol, E., Christian, W., Crossland, S., Faust, S., Gabbay, F., and Gent, N. (2022). Academy of Medical Royal Colleges Statement on the Initial Antimicrobial Treatment of Sepsis, Version 2.0, Academy of Medical Royal Colleges. Available online: https:\/\/www.aomrc.org.uk\/wp-content\/uploads\/2022\/10\/Statement_on_the_initial_antimicrobial_treatment_of_sepsis_V2_1022.pdf."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1001\/jama.2023.0340","article-title":"The Importance of Shifting Sepsis Quality Measures From Processes to Outcomes","volume":"329","author":"Klompas","year":"2023","journal-title":"JAMA"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"505","DOI":"10.1093\/cid\/ciad447","article-title":"Improving Sepsis Outcomes in the Era of Pay-for-Performance and Electronic Quality Measures: A Joint IDSA\/ACEP\/PIDS\/SHEA\/SHM\/SIDP Position Paper","volume":"78","author":"Rhee","year":"2024","journal-title":"Clin. Infect. Dis."},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Mancini, B., Liu, J., Samuelsen, A., Howrylak, J.A., Schultz, L., and Bonavia, A.S. (2023). Comparing long-term prognosis in chronic critically ill patients: A case series study of medical versus surgical sepsis. Medicina, 59.","DOI":"10.3390\/medicina59091617"},{"key":"ref_44","first-page":"1","article-title":"Searching for highly sensitive and specific biomarkers for sepsis: State-of-the-art in post-mortem diagnosis of sepsis through immunohistochemical analysis","volume":"33","author":"Maiese","year":"2019","journal-title":"Int. J. Immunopathol. Pharmacol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"763","DOI":"10.1016\/0895-4356(91)90128-V","article-title":"Likelihood ratios with confidence: Sample size estimation for diagnostic test studies","volume":"44","author":"Simel","year":"1991","journal-title":"J. Clin. Epidemiol."}],"container-title":["Diseases"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2079-9721\/14\/9\/319\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T04:30:24Z","timestamp":1788409824000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2079-9721\/14\/9\/319"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,1]]},"references-count":45,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2026,9]]}},"alternative-id":["diseases14090319"],"URL":"https:\/\/doi.org\/10.3390\/diseases14090319","relation":{},"ISSN":["2079-9721"],"issn-type":[{"value":"2079-9721","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,1]]}}}