Early Biomarkers in Sepsis: Can We Diagnose Before It’s Too Late? – A Review on CRP, Procalcitonin, Presepsin, IL-6, and Novel Biomarkers

Authors

Sakthi Shree B

Student, III BSc Physician assistant, MMM College of Health Sciences (Chennai)

A Amal Rickey

Student, III BSc Physician assistant, MMM College of Health Sciences (Chennai)

Bharathi B

Associate Professor- Microbiology, MMM College of Health Sciences (Chennai)

Deepa C. Philip

Principal, MMM College of Health Sciences (Chennai)

Article Information

DOI: 10.51244/IJRSI.2025.1210000189

Subject Category: Microbiology

Volume/Issue: 12/10 | Page No: 2133-2137

Publication Timeline

Submitted: 2025-10-07

Accepted: 2025-10-13

Published: 2025-11-14

Abstract

Sepsis remains a leading cause of morbidity and mortality worldwide, with early diagnosis critical for improving outcomes. Conventional biomarkers such as C-reactive protein (CRP) and procalcitonin (PCT) aid in diagnosis but lack sufficient sensitivity and specificity, particularly in culture-negative cases. Emerging biomarkers, including interleukin-6 (IL-6), pentraxin 3 (PTX3), suPAR, and soluble triggering receptor expressed on myeloid cells-1 (sTREM-1), provide additional insight but are limited when used alone. Presepsin (sCD14-ST), a cleavage fragment of CD14, rises within 2–3 hours of infection and shows strong diagnostic and prognostic value. Evidence from emergency department studies demonstrates higher sensitivity and specificity for presepsin compared to PCT, especially in culture-negative sepsis. Combined use of presepsin with PCT enhances diagnostic yield and supports a multimarker strategy. Despite promising findings, assay variability and influence of renal dysfunction remain challenges. Future multicenter studies are needed to establish standardized cut-offs and validate its integration into clinical practice.

Keywords

Sepsis, Biomarkers, Presepsin, Procalcitonin

Downloads

References

1. Bone RC. Sepsis: the new concepts. Chest. 1992;101:1644–1655. [Google Scholar] [Crossref]

2. Evans L, Rhodes A, Alhazzani W, Antonelli M, Coopersmith CM, French C, Machado FR, McIntyre L, Ostermann M, Prescott HC, Schorr CA, Simpson SQ, Wiersinga WJ, Alshamsi F, Angus DC, Arabi YM, Azevedo LCP, Beale R, Beilman G, Belley-Cote E, Beuret P, et al. Surviving sepsis campaign: international guidelines for management of sepsis and septic shock 2021. Intensive Care Med. 2021;47:1181–1247. [Google Scholar] [Crossref]

3. Rudd KE, Johnson SC, Agesa KM, Shackelford KA, Tsoi D, Kievlan DR, Colombara DV, Ikuta KS, Kissoon N, Finfer S, Fleischmann-Struzek C, Machado FR, Reinhart KK, Seymour CW, Watson RS, West TE, Marinho F, Hay SI, Lozano R, Murray CJL. Global, regional, and national sepsis incidence and mortality, 1990–2017. Lancet. 2020;395:200–211. [Google Scholar] [Crossref]

4. Takeuchi O, Akira S. Pattern recognition receptors and inflammation. Cell. 2010;140:805–820. [Google Scholar] [Crossref]

5. Bone RC. The pathogenesis of sepsis. Ann Intern Med. 1991;115:457–469. [Google Scholar] [Crossref]

6. Bone RC. Immunologic dissonance: a continuing evolution in our understanding of the systemic inflammatory response syndrome [SIRS] and the multiple organ dysfunction syndrome [MODS]. Ann Intern Med. 1996;125:680–687. [Google Scholar] [Crossref]

7. Andersson U, Tracey KJ. HMGB1 in sepsis. Crit Care Med. 2011;39:1169–1171. [Google Scholar] [Crossref]

8. Ward PA. Sepsis, apoptosis and complement. Biochem Pharmacol. 2008;76:1383–1388. [Google Scholar] [Crossref]

9. Phua J, Ngerng WJ, See KC, Tay CK, Kiong T, Lim HF, Chew MY, Yip HS, Tan A, Tan CH, Mukhopadhyay A, Lee KH. Characteristics and outcomes of culture-negative versus culture-positive severe sepsis. Crit Care. 2013;17:R202. [Google Scholar] [Crossref]

10. Vincent JL, Opal SM, Marshall JC, Tracey KJ. Biomarkers in sepsis. Crit Care Clin. 2020;36:255–272. [Google Scholar] [Crossref]

11. Pierrakos C, Vincent JL. Sepsis biomarkers: a review. Crit Care. 2010;14:R15. [Google Scholar] [Crossref]

12. Assicot M, Gendrel D, Carsin H, Raymond J, Guilbaud J, Bohuon C. High serum procalcitonin concentrations in patients with sepsis and infection. Lancet. 1993;341:515–518. [Google Scholar] [Crossref]

13. Kibe S, Adams K, Barlow G. Diagnostic and prognostic biomarkers of sepsis in critical care. J Antimicrob Chemother. 2011;66[Suppl 2]:ii33–ii40. [Google Scholar] [Crossref]

14. Monneret G, Venet F, Pachot A, Lepape A. Sepsis biomarkers: time for a reappraisal. Ann Intensive Care. 2021;11:62. [Google Scholar] [Crossref]

15. Masson S, Caironi P, Spanuth E, Thomae R, Panigada M, Sangiorgi G, Fumagalli R, Mauri T, Isgrò S, Fanizza C, Romero M, Tognoni G, Pesenti A, Latini R. Circulating presepsin in severe sepsis and septic shock. Crit Care. 2015;19:400. [Google Scholar] [Crossref]

16. Ulla M, Pizzolato E, Lucchiari M, Loiacono M, Soardo F, Forno D, Morello F, Lupia E, Moiraghi C, Mengozzi G, Battista S, Lauria G, Cantaluppi V, Navalesi P, De Rosa FG. Diagnostic and prognostic value of presepsin in sepsis. BMC Infect Dis. 2013;13:282. [Google Scholar] [Crossref]

17. Nagata T, Yasuda Y, Ando M, Abe T, Katsuno T, Kato S, Maruyama S, Ito Y, Hishida A, Matsuo S. Presepsin as a biomarker in sepsis. Crit Care. 2014;18:R120. [Google Scholar] [Crossref]

18. Kweon OJ, Choi JH, Park SK, Park AJ. Presepsin as a prognostic marker for sepsis. Clin Chim Acta. 2014;436:141–147. [Google Scholar] [Crossref]

19. Behnes M, Bertsch T, Lepiorz D, Lang S, Trinkmann F, Brueckmann M, Borggrefe M, Hoffmann U. Diagnostic and prognostic utility of soluble CD14 subtype [presepsin] in sepsis and systemic inflammatory response syndrome [SIRS]. Clin Chim Acta. 2014;430:66–72. [Google Scholar] [Crossref]

20. Masson S, Caironi P, Fanizza C, Carrer S, Caricato A, Fassini P, Franzosi MG, Latini R, Tognoni G, Pesenti A, Gattinoni L. Presepsin for risk stratification in sepsis. Clin Chem Lab Med. 2014;52:123–133. [Google Scholar] [Crossref]

21. Liu B, Chen YX, Yin Q, Zhao YZ, Li CS. Diagnostic value and prognostic evaluation of Presepsin for sepsis in an emergency department. Crit Care. 2013;17:R244. [Google Scholar] [Crossref]

22. Piccioni A, Baroni S, Rozzi G, Belvederi F, Leggeri S, Spagnuolo F, Novelli M, Pignataro G, Candelli M, Covino M, Gasbarrini A, Franceschi F. Evaluation of Presepsin for Early Diagnosis of Sepsis in the Emergency Department. J Clin Med. 2025;14[7]:2480. https://doi.org/10.3390/jcm14072480. [Google Scholar] [Crossref]

Metrics

Views & Downloads

Similar Articles