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Comparison of the accuracy of neutrophil CD64 and C-reactive protein as a single test for the early detection of neonatal sepsis

  • Choo, Young-Kwang (Department of Pediatrics, Kangwon National University Hospital, Kangwon National University School of Medicine) ;
  • Cho, Hyun-Seok (Department of Pediatrics, Kangwon National University Hospital, Kangwon National University School of Medicine) ;
  • Seo, In-Bum (Department of Clinical Diagnosis, Kangwon National University Hospital, Kangwon National University School of Medicine) ;
  • Lee, Hyeon-Soo (Department of Pediatrics, Kangwon National University Hospital, Kangwon National University School of Medicine)
  • Received : 2011.06.16
  • Accepted : 2011.11.12
  • Published : 2012.01.15

Abstract

Purpose: Early identification of neonatal sepsis is a global issue because of limitations in diagnostic procedures. The objective of this study was to compare the diagnostic accuracy of neutrophil CD64 and C-reactive protein (CRP) as a single test for the early detection of neonatal sepsis. Methods: A prospective study enrolled newborns with documented sepsis (n=11), clinical sepsis (n=12) and control newborns (n=14). CRP, neutrophil CD64, complete blood counts and blood culture were taken at the time of the suspected sepsis for the documented or clinical group and at the time of venipuncture for laboratory tests in control newborns. Neutrophil CD64 was analyzed by flow cytometry. Results: CD64 was significantly elevated in the groups with documented or clinical sepsis, whereas CRP was not significantly increased compared with controls. For documented sepsis, CD64 and CRP had a sensitivity of 91% and 9%, a specificity of 83% and 83%, a positive predictive value of 83% and 33% and a negative predictive value of 91% and 50%, respectively, with a cutoff value of 3.0 mg/dL for CD64 and 1.0 mg/dL for CRP. The area under the receiver-operating characteristic curves for CD64 index and CRP were 0.955 and 0.527 ($P$ <0.01), respectively. Conclusion: These preliminary data show that diagnostic accuracy of CD64 is superior to CRP when measured at the time of suspected sepsis, which implies that CD64 is a more reliable marker for the early identification of neonatal sepsis as a single determination compared with CRP.

Keywords

References

  1. Bizzarro MJ, Raskind C, Baltimore RS, Gallagher PG. Seventy-five years of neonatal sepsis at Yale: 1928-2003. Pediatrics 2005;116:595-602.
  2. Lawn JE, Wilczynska-Ketende K, Cousens SN. Estimating the causes of 4 million neonatal deaths in the year 2000. Int J Epidemiol 2006;35:706-18.
  3. Ng PC, Cheng SH, Chui KM, Fok TF, Wong MY, Wong W, et al. Diagnosis of late onset neonatal sepsis with cytokines, adhesion molecule, and C-reactive protein in preterm very low birthweight infants. Arch Dis Child Fetal Neonatal Ed 1997;77:F221-7.
  4. Stoll BJ, Holman RC, Schuchat A. Decline in sepsis-associated neonatal and infant deaths in the United States, 1979 through 1994. Pediatrics 1998;102:e18.
  5. 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.
  6. Batlivala SP. Focus on diagnosis: the erythrocyte sedimentation rate and the C-reactive protein test. Pediatr Rev 2009;30:72-4.
  7. Ng PC, Lam HS. Diagnostic markers for neonatal sepsis. Curr Opin Pediatr 2006;18:125-31.
  8. Hoffmeyer F, Witte K, Schmidt RE. The high-affinity Fc gamma RI on PMN: regulation of expression and signal transduction. Immunology 1997;92:544-52.
  9. Dilli D, Oguz SS, Dilmen U, Koker MY, Kizilgun M. Predictive values of neutrophil CD64 expression compared with interleukin-6 and C-reactive protein in early diagnosis of neonatal sepsis. J Clin Lab Anal 2010;24:363-70.
  10. Groselj-Grenc M, Ihan A, Pavcnik-Arnol M, Kopitar AN, Gmeiner- Stopar T, Derganc M. Neutrophil and monocyte CD64 indexes, lipopoly saccharide-binding protein, procalcitonin and C-reactive protein in sepsis of critically ill neonates and children. Intensive Care Med 2009;35:1950-8.
  11. Bhandari V, Wang C, Rinder C, Rinder H. Hematologic profile of sepsis in neonates: neutrophil CD64 as a diagnostic marker. Pediatrics 2008;121: 129-34.
  12. Ng PC, Li G, Chui KM, Chu WC, Li K, Wong RP, et al. Neutrophil CD64 is a sensitive diagnostic marker for early-onset neonatal infection. Pediatr Res 2004;56:796-803.
  13. Manroe BL, Weinberg AG, Rosenfeld CR, Browne R. The neonatal blood count in health and disease. I. Reference values for neutrophilic cells. J Pediatr 1979;95:89-98.
  14. Gonzalez BE, Mercado CK, Johnson L, Brodsky NL, Bhandari V. Early markers of late-onset sepsis in premature neonates: clinical, hematological and cytokine profile. J Perinat Med 2003;31:60-8.
  15. Smulian JC, Bhandari V, Campbell WA, Rodis JF, Vintzileos AM. Value of umbilical artery and vein levels of interleukin-6 and soluble intracellular adhesion molecule-1 as predictors of neonatal hematologic indices and suspected early sepsis. J Matern Fetal Med 1997;6:254-9.
  16. Morsy AA, Elshall LY, Zaher MM, Abd Elsalam M, Nassr AE. CD64 cell surface expression on neutrophils for diagnosis of neonatal sepsis. Egypt J Immunol 2008;15:53-61.
  17. Da Silva O, Ohlsson A, Kenyon C. Accuracy of leukocyte indices and C-reactive protein for diagnosis of neonatal sepsis: a critical review. Pediatr Infect Dis J 1995;14:362-6.
  18. Rodwell RL, Leslie AL, Tudehope DI. Early diagnosis of neonatal sepsis using a hematologic scoring system. J Pediatr 1988;112:761-7.
  19. Cornbleet PJ. Clinical utility of the band count. Clin Lab Med 2002;22:101-36.
  20. Newman TB, Puopolo KM, Wi S, Draper D, Escobar GJ. Interpreting complete blood counts soon after birth in newborns at risk for sepsis. Pediatrics 2010;126:903-9.
  21. Wagle S, Grauaug A, Kohan R, Evans SF. C-reactive protein as a diagnostic tool of sepsis in very immature babies. J Paediatr Child Health 1994;30:40-4.
  22. Fjaertoft G, Hakansson L, Ewald U, Foucard T, Venge P. Neutrophils from term and preterm newborn infants express the high affinity Fcgammareceptor I (CD64) during bacterial infections. Pediatr Res 1999;45:871-6.
  23. Cohen S, Burns RC. Pathways of the pulp. 8th ed. St. Louis: Mosby, 2002:465.
  24. de Haas M, Vossebeld PJ, von dem Borne AE, Roos D. Fc gamma receptors of phagocytes. J Lab Clin Med 1995;126:330-41.
  25. Sanchez-Mejorada G, Rosales C. Signal transduction by immunoglobulin Fc receptors. J Leukoc Biol 1998;63:521-33.
  26. Roitt I, Brostoff J, Male DK. Immunology. 6th ed. New York: Mosby, 2001:5.
  27. 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.
  28. Rowley AH, Wald ER. Incubation period necessary to detect bacteremia in neonates. Pediatr Infect Dis 1986;5:590-1.
  29. Janjindamai W, Phetpisal S. Time to positivity of blood culture in newborn infants. Southeast Asian J Trop Med Public Health 2006;37:171-6.
  30. Jardine L, Davies MW, Faoagali J. Incubation time required for neonatal blood cultures to become positive. J Paediatr Child Health 2006;42:797-802.

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