Jump to ContentJump to Main Navigation
Show Summary Details
More options …

Clinical Chemistry and Laboratory Medicine (CCLM)

Published in Association with the European Federation of Clinical Chemistry and Laboratory Medicine (EFLM)

Editor-in-Chief: Plebani, Mario

Ed. by Gillery, Philippe / Lackner, Karl J. / Lippi, Giuseppe / Melichar, Bohuslav / Payne, Deborah A. / Schlattmann, Peter

IMPACT FACTOR 2017: 3.556

CiteScore 2017: 2.34

SCImago Journal Rank (SJR) 2017: 1.114
Source Normalized Impact per Paper (SNIP) 2017: 1.188

See all formats and pricing
More options …
Volume 51, Issue 4


Polymorphic mononuclear neutrophils CD64 index for diagnosis of sepsis in postoperative surgical patients and critically ill patients

Jeroen H. Gerrits / Pamela M.J. McLaughlin / Bert N. Nienhuis / Jan W. Smit / Bert Loef
Published Online: 2012-10-06 | DOI: https://doi.org/10.1515/cclm-2012-0279


Background: Surface neutrophil CD64 expression is upregulated in patients with bacterial infection. As it was suggested that the CD64 index could be used to detect sepsis in hospitalized patients, we questioned whether the CD64 index could discriminate between septic patients and postoperative surgical patients, defined as systemic inflammatory response syndrome (SIRS), both admitted at the intensive care unit (ICU). Furthermore, we wondered whether the CD64 index was an improved diagnostic compared to standard assays used at the laboratory. For this, outclinic (OC) patients were included as controls.

Methods: The Leuko64™ assay was used to determine the CD64 index in residual EDTA blood samples from selected septic patients (n=25), SIRS patients (n=19), and OC patients (n=24). Additionally, WBC count, neutrophilic and eosinophilic granulocyte count, C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) were measured simultaneously.

Results: The CD64 index was higher in septic patients compared to both the SIRS and OC group (p<0.0001). In addition, the WBC count, neutrophil count, ESR and CRP were also higher in septic patients than the OC group (p<0.0001). However, only the WBC count, eosinopenia, and ESR were comparable between the SIRS and the sepsis group and proved to be discriminative to the OC group (p<0.05). The CD64 index demonstrated higher sensitivity and specificity than CRP, WBC count, neutrophilic and eosinophilic granulocyte count, and ESR.

Conclusions: A high CD64 index was found in septic intensive care patients, while a low CD64 index was observed in OC and SIRS patients, demonstrating that the CD64 index can be used for routine diagnostics in the ICU setting.

Keywords: bacterial infection; CD64; diagnostic accuracy sepsis; intensive care unit; systemic inflammatory response syndrome


  • 1.

    Dellinger RP, Levy MM, Carlet JM, Bion J, Parker MM, Jaeschke R, et al. Surviving sepsis campaign: international guidelines for management of severe sepsis and septic shock: 2008. Crit Care Med 2008;36:296–327.CrossrefPubMedGoogle Scholar

  • 2.

    Stearns-Kurosawa DJ, Osuchowski MF, Valentine C, Kurosawa S, Remick DG. The pathogenesis of sepsis. Annu Rev Pathol 2011;6:19–48.CrossrefGoogle Scholar

  • 3.

    Russell JA. Management of sepsis. N Engl J Med 2006;355: 1699–713.CrossrefPubMedGoogle Scholar

  • 4.

    Hoffmann JJ. Neutrophil CD64: a diagnostic marker for infection and sepsis. Clin Chem Lab Med 2009;47:903–16.Web of ScienceGoogle Scholar

  • 5.

    Chan T, Gu F. Early diagnosis of sepsis using serum biomarkers. Expert Rev Mol Diagn 2011;11:487–96.Web of SciencePubMedCrossrefGoogle Scholar

  • 6.

    Wang P, Yang Z, He Y, Shu C. Pitfalls in the rapid diagnosis of positive blood culture. Rev Med Microbiol 2010;21:39–43.CrossrefGoogle Scholar

  • 7.

    Carrol ED, Thomson AP, Hart CA. Procalcitonin as a marker of sepsis. Int J Antimicrob Agents 2002;20:1–9.CrossrefPubMedGoogle Scholar

  • 8.

    Schuerholz T, Marx G. Management of sepsis. Minerva Anestesiol 2008;74:181–95.PubMedGoogle Scholar

  • 9.

    Eissa D, Carton EG, Buggy DJ. Anaesthetic management of patients with severe sepsis. Br J Anaesth 2010;105:734–43.PubMedCrossrefGoogle Scholar

  • 10.

    Abidi K, Khoudri I, Belayachi J, Madani N, Zekraoui A, Zeggwagh AA, et al. Eosinopenia is a reliable marker of sepsis on admission to medical intensive care units. Crit Care 2008;12:R59.CrossrefGoogle Scholar

  • 11.

    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;130:654–61.Google Scholar

  • 12.

    Nuutila J, Hohenthal U, Laitinen I, Kotilainen P, Rajamaki A, Nikoskelainen J, et al. Simultaneous quantitative analysis of FcgammaRI (CD64) expression on neutrophils and monocytes: a new, improved way to detect infections. J Immunol Methods 2007;328:189–200.CrossrefWeb of ScienceGoogle Scholar

  • 13.

    Nuutila J. The novel applications of the quantitative analysis of neutrophil cell surface FcgammaRI (CD64) to the diagnosis of infectious and inflammatory diseases. Curr Opin Infect Dis 2010;23:268–74.CrossrefWeb of ScienceGoogle Scholar

  • 14.

    Levy MM, Fink MP, Marshall JC, Abraham E, Angus D, Cook D, et al. 2001 SCCM/ESICM/ACCP/ATS/SIS International Sepsis Definitions Conference. Crit Care Med 2003;31:1250–6.Google Scholar

  • 15.

    Arnon S, Litmanovitz I. Diagnostic tests in neonatal sepsis. Curr Opin Infect Dis 2008;21:223–7.CrossrefPubMedWeb of ScienceGoogle Scholar

  • 16.

    Beekmann SE, Diekema DJ, Doern GV. Determining the clinical significance of coagulase-negative staphylococci isolated from blood cultures. Infect Control Hosp Epidemiol 2005;26:559–66.Google Scholar

  • 17.

    Richter SS, Beekmann SE, Croco JL, Diekema DJ, Koontz FP, Pfaller MA, et al. Minimizing the workup of blood culture contaminants: implementation and evaluation of a laboratory-based algorithm. J Clin Microbiol 2002;40:2437–44.PubMedCrossrefGoogle Scholar

  • 18.

    Standage SW, Wong HR. Biomarkers for pediatric sepsis and septic shock. Expert Rev Anti Infect Ther 2011;9:71–9.Web of ScienceGoogle Scholar

  • 19.

    Cid J, Aguinaco R, Sanchez R, Garcia-Pardo G, Llorente A. Neutrophil CD64 expression as marker of bacterial infection: a systematic review and meta-analysis. J Infect 2010;60:313–9.Web of ScienceCrossrefGoogle Scholar

  • 20.

    Groselj-Grenc M, Ihan A, Pavcnik-Arnol M, Kopitar AN, Gmeiner-Stopar T, Derganc M. Neutrophil and monocyte CD64 indexes, lipopolysaccharide-binding protein, procalcitonin and C-reactive protein in sepsis of critically ill neonates and children. Intensive Care Med 2009;35:1950–8.Web of ScienceGoogle Scholar

  • 21.

    Fjaertoft G, Hakansson LD, Pauksens K, Sisask G, Venge P. Neutrophil CD64 (FcgammaRI) expression is a specific marker of bacterial infection: a study on the kinetics and the impact of major surgery. Scand J Infect Dis 2007;39: 525–35.CrossrefGoogle Scholar

  • 22.

    Fischer G, Schneider EM, Moldawer LL, Karcher C, Barth E, Suger-Wiedeck H, et al. CD64 surface expression on neutrophils is transiently upregulated in patients with septic shock. Intensive Care Med 2001;27:1848–52.Google Scholar

  • 23.

    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;47:3914–9.CrossrefGoogle Scholar

  • 24.

    Davis BH, Bigelow NC. Comparison of neutrophil CD64 expression, manual myeloid immaturity counts, and automated hematology analyzer flags as indicators of infection or sepsis. Lab Hematol 2005;11:137–47.CrossrefGoogle Scholar

  • 25.

    Gros A, Roussel M, Sauvadet E, Gacouin A, Marque S, Chimot L, et al. The sensitivity of neutrophil CD64 expression as a biomarker of bacterial infection is low in critically ill patients. Intensive Care Med 2012;38:445–52.Web of ScienceGoogle Scholar

  • 26.

    Mokart D, Merlin M, Sannini A, Brun JP, Delpero JR, Houvenaeghel G, et al. Procalcitonin, interleukin 6 and systemic inflammatory response syndrome (SIRS): early markers of postoperative sepsis after major surgery. Br J Anaesth 2005;94:767–73.PubMedCrossrefGoogle Scholar

  • 27.

    Oda S, Hirasawa H, Shiga H, Nakanishi K, Matsuda K, Nakamua M. Sequential measurement of IL-6 blood levels in patients with systemic inflammatory response syndrome (SIRS)/sepsis. Cytokine 2005;29:169–75.PubMedCrossrefGoogle Scholar

  • 28.

    Reinhart K, Meisner M. Biomarkers in the critically ill patient: procalcitonin. Crit Care Clin 2011;27:253–63.PubMedCrossrefGoogle Scholar

  • 29.

    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;7:210–7.Web of ScienceCrossrefPubMedGoogle Scholar

  • 30.

    Becker KL, Snider R, Nylen ES. Procalcitonin assay in systemic inflammation, infection, and sepsis: clinical utility and limitations. Crit Care Med 2008;36:941–52.CrossrefWeb of SciencePubMedGoogle Scholar

  • 31.

    Scheller J, Chalaris A, Schmidt-Arras D, Rose-John S. The pro- and anti-inflammatory properties of the cytokine interleukin-6. Biochim Biophys Acta 2011;1813:878–88.Web of ScienceGoogle Scholar

  • 32.

    Limper M, de Kruif MD, Duits AJ, Brandjes DP, van Gorp EC. The diagnostic role of procalcitonin and other biomarkers in discriminating infectious from non-infectious fever. J Infect 2010;60:409–16.CrossrefPubMedWeb of ScienceGoogle Scholar

  • 33.

    Osuchowski MF, Welch K, Siddiqui J, Remick DG. Circulating cytokine/inhibitor profiles reshape the understanding of the SIRS/CARS continuum in sepsis and predict mortality. J Immunol 2006;177:1967–74.PubMedGoogle Scholar

  • 34.

    Tschaikowsky K, Hedwig-Geissing M, Braun GG, Radespiel-Troeger M. Predictive value of procalcitonin, interleukin-6, and C-reactive protein for survival in postoperative patients with severe sepsis. J Crit Care 2011;26:54–64.CrossrefWeb of ScienceGoogle Scholar

About the article

Corresponding author: Jeroen H. Gerrits, LabNoord, Clinical Chemistry Laboratory, Martini Hospital, Room 5D106, Van Swietenplein 1, 9728 NT Groningen, The Netherlands, Phone: +31 50 5247594, Fax: +31 50 5246676

Received: 2012-05-04

Accepted: 2012-08-28

Published Online: 2012-10-06

Published in Print: 2013-04-01

Citation Information: Clinical Chemistry and Laboratory Medicine, Volume 51, Issue 4, Pages 897–905, ISSN (Online) 1437-4331, ISSN (Print) 1434-6621, DOI: https://doi.org/10.1515/cclm-2012-0279.

Export Citation

©2013 by Walter de Gruyter Berlin Boston.Get Permission

Citing Articles

Here you can find all Crossref-listed publications in which this article is cited. If you would like to receive automatic email messages as soon as this article is cited in other publications, simply activate the “Citation Alert” on the top of this page.

Alberto García-Salido, Ana Serrano-González, Juan Casado-Flores, Montserrat Sierra-Colomina, Amelia Martínez de Azagra-Garde, María Ángeles García-Teresa, Gustavo J. Melen, and Manuel Ramírez-Orellana
Journal of Leukocyte Biology, 2018
Bethany M. Biron, Alfred Ayala, and Joanne L. Lomas-Neira
Biomarker Insights, 2015, Volume 10s4, Page BMI.S29519
Sarah Djebara, Patrick Biston, Emmanuel Fossé, Anne Daper, Marc Joris, Karim Zouaoui Boudjeltia, Christophe Lelubre, Philippe Cauchie, and Michael Piagnerelli
SHOCK, 2017, Volume 47, Number 2, Page 158
Yong Liu, Jun-huan Hou, Qing Li, Kui-jun Chen, Shu-Nan Wang, and Jian-min Wang
SpringerPlus, 2016, Volume 5, Number 1
Fabio E. Ospina, Alex Echeverri, Diana Zambrano, Juan-Pablo Suso, Javier Martínez-Blanco, Carlos A. Cañas, and Gabriel J. Tobón
Rheumatology, 2016, Page kew340
Masumeh Taheri, Jalil Mehrzad, Reza Afshari, Massoud Saleh-Moghaddam, and Mohamad Hosein Mahmudy Gharaie
Journal of Immunotoxicology, 2016, Volume 13, Number 5, Page 686
J. Burgos, I. Los-Arcos, D. Álvarez de la Sierra, V. Falcó, A. Aguiló, I. Sánchez, B. Almirante, and M. Martinez-Gallo
European Journal of Clinical Microbiology & Infectious Diseases, 2016, Volume 35, Number 9, Page 1411
Toru Doi, Tokuhide Doi, Naohiro Kawamura, Toshihiro Matsui, Akiko Komiya, Zaika Tei, Gaku Niitsuma, and Junichi Kunogi
Journal of Orthopaedic Science, 2016, Volume 21, Number 4, Page 546
Xiao Wang, Zhong-Yun Li, Ling Zeng, An-Qiang Zhang, Wei Pan, Wei Gu, and Jian-Xin Jiang
Critical Care, 2015, Volume 19, Number 1
Li Qian, Shi-Bao Li, Yan Zhou, Shi-Jie Teng, and Jing-Jing Guo
American Journal of Reproductive Immunology, 2015, Volume 74, Number 4, Page 309
J. Jämsä, V. Huotari, E.-R. Savolainen, H. Syrjälä, and T. Ala-kokko
Acta Anaesthesiologica Scandinavica, 2015, Volume 59, Number 7, Page 881
Jia-Feng Wang, Jin-Bao Li, Yan-Jun Zhao, Wen-Jing Yi, Jin-Jun Bian, Xiao-Jian Wan, Ke-Ming Zhu, and Xiao-Ming Deng
Anesthesiology, 2015, Volume 122, Number 4, Page 852
Nozomi Otsuki, Hiroshi Tsutani, Toshihiro Matsui, Hiromichi Iwasaki, and Takanori Ueda
Geriatrics & Gerontology International, 2016, Volume 16, Number 3, Page 307
B.H. Siegler, S. Weiterer, C. Lichtenstern, D. Stumpp, T. Brenner, S. Hofer, M.A. Weigand, and F. Uhle
Der Anaesthesist, 2014, Volume 63, Number 8-9, Page 678
Qingquan Chen, Heng Xue, Min Chen, Feng Gao, Jianping Xu, Qicai Liu, Xiulin Yang, Lie Zheng, and Hong Chen
Inflammation, 2014, Volume 37, Number 5, Page 1751

Comments (0)

Please log in or register to comment.
Log in