Biomarkers to diagnose sepsis

  • Anja Žargaj University Clinic of Respiratory and Allergic Diseases Golnik Faculty of Medicine Ljubljana
  • Peter Korošec Univerzitetna klinika za pljučne bolezni in alergijo, Golnik
  • Franci Šifrer Univerzitetna klinika za pljučne bolezni in alergijo, Golnik
  • Mitja Košnik 1 Univerzitetna klinika za pljučne bolezni in alergijo, Golnik2 Medicinska fakulteta v Ljubljani
Keywords: sepsis, CD 64 antigen, C-reactive protein, procalcitonin, neutrophil

Abstract

Background: Sepsis is a life-threatening organ dysfunction that arises when a host responds insufficiently to an infection as bacteria enter the bloodstream. In recent years, SOFA scoring system has been used to identify poor organ functioning. Microbiological blood tests represent a gold standard in sepsis diagnostics. Reliable biomarkers for early detection of sepsis would greatly facilitate rapid and efficient treatment of sepsis.

Methods: In a prospective non-interventional study we studied the diagnostic value of C-reactive protein (CRP), procalcitonin (PCT), neutrophil CD64 index, neutrophil granulocyte count and immature neutrophil count in patients with sepsis and patients with severe infection without sepsis. A total of 46 consecutive intensive-care-unit patients admitted for severe infection and 10 healthy controls were included. The patients were treated routinely according to the principles of good clinical practice.

Results: Statistically significant differences between the two groups of patients have been established for the CD64 index, the PCT and the immature neutrophil count, whereas the differences in the CRP and the neutrophil granulocyte count are statistically non-significant. The highest diagnostic values were measured for the immature neutrophil count (AUC 0.91) and PCT (AUC 0.84). The combination of biomarkers has been shown to have same predictive values as the immature neutrophil count and the PCT.

Downloads

Download data is not yet available.

References

Hall MJ, Williams SN, DeFrances CJ, Golosinskiy A. Inpatient care for septicemia or sepsis: a challenge for patients and hospitals. NCHS Data Brief. 2011 Jun;(62):1–8. PMID:22142805

Beovic B, Hladnik Z, Pozenel P, Siuka D; Slovenian Severe Sepsis Study Group. Epidemiology of severe sepsis in Slovenian intensive care units for adults. J Chemother. 2008 Feb;20(1):134–6. https://doi.org/10.1179/joc.2008.20.1.134 PMID:18343757

Wang JY, Chen YX, Guo SB, Mei X, Yang P. Predictive performance of quick Sepsis-related Organ Failure Assessment for mortality and intensive care unit admission in patients with infection at the ED. Am J Emerg Med. 2016 Jun;(16):30227–3.

Yeh RW, Sidney S, Chandra M, Sorel M, Selby JV, Go AS. Population trends in the incidence and outcomes of acute myocardial infarction. N Engl J Med. 2010 Jun;362(23):2155–65. https://doi.org/10.1056/NEJMoa0908610 PMID:20558366

Torio CM, Andrews RM. National Inpatient Hospital Costs: Te Most Expensive Conditions by Payer, 2011: Statistical Brief #160. Healthcare Cost and Utilization Project (HCUP) Statistical Briefs [Internet]. 2006-2013. Available from: http://www.ncbi.nlm.nih.gov/books/NBK169005/

Lever A, Mackenzie I. Sepsis: defnition, epidemiology, and diagnosis. BMJ. 2007 Oct;335(7625):879–83. https://doi.org/10.1136/bmj.39346.495880.AE PMID:17962288

Faix JD. Biomarkers of sepsis. Crit Rev Clin Lab Sci. 2013 Jan-Feb;50(1):23–36. https://doi.org/10.3109/10408363.2013.764490 PMID:23480440

Singer M, Deutschman CS, Seymour CW, Shankar-Hari M, Annane D, Bauer M, et al. Te Tird International Consensus Defnitions for Sepsis and Septic Shock (Sepsis-3. JAMA. 2016 Feb;315(8):801–10. https://doi.org/10.1001/jama.2016.0287 PMID:26903338

Vincent JL, Moreno R, Takala J, Willatts S, De Mendonça A, Bruining H, et al. Te SOFA (Sepsis-related Organ Failure Assessment) score to describe organ dysfunction/failure. On behalf of the Working Group on Sepsis-Related Problems of the European Society of Intensive Care Medicine. Intensive Care Med. 1996 Jul;22(7):707–10. https://doi.org/10.1007/BF01709751 PMID:8844239

Martin GS, Mannino DM, Eaton S, Moss M. Te epidemiology of sepsis in the United States from 1979 through 2000. N Engl J Med. 2003 Apr;348(16):1546–54. https://doi.org/10.1056/NEJMoa022139 PMID:12700374

Kaukonen KM, Bailey M, Suzuki S, Pilcher D, Bellomo R. Mortality related to severe sepsis and septic shock among critically ill patients in Australia and New Zealand, 2000-2012. JAMA. 2014 Apr;311(13):1308–16. https://doi.org/10.1001/jama.2014.2637 PMID:24638143

Klein Klouwenberg PM, Ong DS, Bonten MJ, Cremer OL. Classifcation of sepsis, severe sepsis and septic shock: the impact of minor variations in data capture and defnition of SIRS criteria. Intensive Care Med. 2012 May;38(5):811–9. https://doi.org/10.1007/s00134-012-2549-5 PMID:22476449

Casserly B, Phillips GS, Schorr C, Dellinger RP, Townsend SR, Osborn TM, et al. Lactate measurements in sepsis-induced tissue hypoperfusion: results from the Surviving Sepsis Campaign database. Crit Care Med. 2015 Mar;43(3):567–73. https://doi.org/10.1097/CCM.0000000000000742 PMID:25479113

Kirn TJ, Weinstein MP. Update on blood cultures: how to obtain, process, report, and interpret. Clin Microbiol Infect. 2013 Jun;19(6):513–20. https://doi.org/10.1111/1469-0691.12180 PMID:23490046

Weinstein MP, Towns ML, Quartey SM, Mirrett S, Reimer LG, Parmigiani G, et al. The clinical significance of positive blood cultures in the 1990s: a prospective comprehensive evaluation of the microbiology, epidemiology, and outcome of bacteremia and fungemia in adults. Clin Infect Dis. 1997 Apr;24(4):584–602. https://doi.org/10.1093/clind/24.4.584 PMID:9145732

Pien BC, Sundaram P, Raoof N, Costa SF, Mirrett S, Woods CW, et al. The clinical and prognostic importance of positive blood cultures in adults. Am J Med. 2010 Sep;123(9):819–28. https://doi.org/10.1016/j.amjmed.2010.03.021 PMID:20800151

Standage SW, Wong HR. Biomarkers for pediatric sepsis and septic shock. Expert Rev Anti Infect Ter. 2011 Jan;9(1):71–9. https://doi.org/10.1586/eri.10.154 PMID:21171879

Llewelyn MJ, Berger M, Gregory M, Ramaiah R, Taylor AL, Curdt I, et al. Sepsis biomarkers in unselected patients on admission to intensive or high-dependency care. Crit Care. 2013 Mar;17(2):R60. https://doi.org/10.1186/cc12588 PMID:23531337

Hatzistilianou M. Diagnostic and prognostic role of procalcitonin in infections. Sci World J. 2010 Oct;10:1941–6. https://doi.org/10.1100/tsw.2010.181 PMID:20890583

Adib M, Bakhshiani Z, Navaei F, Saheb Fosoul F, Fouladi S, Kazemzadeh H. Procalcitonin: a reliable marker for the diagnosis of neonatal sepsis. Iran J Basic Med Sci. 2012 Mar;15(2):777–82. PMID:23493845

Hoffmann JJ. Neutrophil CD64 as a sepsis biomarker. Biochem Med (Zagreb. 2011;21(3):282–90. https://doi.org/10.11613/BM.2011.038 PMID:22420242

Davis BH, Olsen SH, Ahmad E, Bigelow NC. Neutrophil CD64 is an improved indicator of infection or sepsis in emergency department patients. Arch Pathol Lab Med. 2006 May;130(5):654–61. PMID:16683883

Groselj-Grenc M, Ihan A, Derganc M. Neutrophil and monocyte CD64 and CD163 expression in critically ill neonates and children with sepsis: comparison of fluorescence intensities and calculated indexes. Mediators Inflamm. 2008;2008:202646. https://doi.org/10.1155/2008/202646 PMID:18604302

Allen E, Bakke AC, Purtzer MZ, Deodhar A. Neutrophil CD64 expression: distinguishing acute inflammatory autoimmune disease from systemic infections. Ann Rheum Dis. 2002 Jun;61(6):522–5. https://doi.org/10.1136/ard.61.6.522 PMID:12006325

Karimollah Hajian-Tilaki, Receiver Operating Characteristic (ROC) Curve Analysis for Medical Diagnostic Test Evaluation. Caspian J Intern Med. 2013;4(2):627–35. PMID:24009950

Zeitoun AA, Gad SS, Attia FM, Abu Maziad AS, Bell EF. Evaluation of neutrophilic CD64, interleukin 10 and procalcitonin as diagnostic markers of early- and late-onset neonatal sepsis. Scand J Infect Dis. 2010 Apr;42(4):299–305. https://doi.org/10.3109/00365540903449832 PMID:20085423

Li S, Huang X, Chen Z, Zhong H, Peng Q, Deng Y, et al. Neutrophil CD64 expression as a biomarker in the early diagnosis of bacterial infection: a meta-analysis. Int J Infect Dis. 2013 Jan;17(1):e12–23. https://doi.org/10.1016/j.ijid.2012.07.017 PMID:22940278

Gerrits JH, McLaughlin PM, Nienhuis BN, Smit JW, Loef B. Polymorphic mononuclear neutrophils CD64 index for diagnosis of sepsis in postoperative surgical patients and critically ill patients. Clin Chem Lab Med. 2013 Apr;51(4):897–905. https://doi.org/10.1515/cclm-2012-0279 PMID:23045384

Cardelli P, Ferraironi M, Amodeo R, Tabacco F, De Blasi RA, Nicoletti M, et al. Evaluation of neutrophil CD64 expression and procalcitonin as useful markers in early diagnosis of sepsis. Int J Immunopathol Pharmacol. 2008 Jan-Mar;21(1):43–9. https://doi.org/10.1177/039463200802100106 PMID:18336730

Patil VK, Morjaria JB, De Villers F, Babu SK. Associations between procalcitonin and markers of bacterial

sepsis. Medicina (Kaunas. 2012;48(8):383–7. PMID:23128457

Gibot S, Béné MC, Noel R, Massin F, Guy J, Cravoisy A, et al. Combination biomarkers to diagnose sepsis in the critically ill patient. Am J Respir Crit Care Med. 2012 Jul;186(1):65–71. https://doi.org/10.1164/rccm.201201-0037OC PMID:22538802

Tang BM, Eslick GD, Craig JC, McLean AS. Accuracy of procalcitonin for sepsis diagnosis in critically ill patients: systematic review and meta-analysis. Lancet Infect Dis. 2007 Mar;7(3):210–7. https://doi.org/10.1016/S1473-3099(07)70052-X PMID:17317602

Gros A, Roussel M, Sauvadet E, Gacouin A, Marqué S, Chimot L, et al. Te sensitivity of neutrophil CD64 expression as a biomarker of bacterial infection is low in critically ill patients. Intensive Care Med. 2012 Mar;38(3):445–52. https://doi.org/10.1007/s00134-012-2483-6 PMID:22310872

Hsu KH, Chan MC, Wang JM, Lin LY, Wu CL. Comparison of Fcγ receptor expression on neutrophils with procalcitonin for the diagnosis of sepsis in critically ill patients. Respirology. 2011 Jan;16(1):152–60. https://doi.org/10.1111/j.1440-1843.2010.01876.x PMID:20946336

Gámez-Díaz LY, Enriquez LE, Matute JD, Velásquez S, Gómez ID, Toro F, et al. Diagnostic accuracy of HMGB-1, sTREM-1, and CD64 as markers of sepsis in patients recently admitted to the emergency department. Acad Emerg Med. 2011 Aug;18(8):807–15. https://doi.org/10.1111/j.1553-2712.2011.01113.x PMID:21762470

Icardi M, Erickson Y, Kilborn S, Stewart B, Grief B, Scharnweber G. CD64 index provides simple and predictive testing for detection and monitoring of sepsis and bacterial infection in hospital patients. J Clin Microbiol. 2009 Dec;47(12):3914–9. https://doi.org/10.1128/JCM.00628-09 PMID:19846647

Published
2018-01-30
How to Cite
1.
Žargaj A, Korošec P, Šifrer F, Košnik M. Biomarkers to diagnose sepsis. TEST ZdravVestn [Internet]. 30Jan.2018 [cited 25Apr.2024];86(11-12):481-92. Available from: http://vestnik-dev.szd.si/index.php/ZdravVest/article/view/2022
Section
Original article