Am J Perinatol 2014; 31(01): 021-030
DOI: 10.1055/s-0033-1334453
Original Article
Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Neutrophil CD64 with Hematologic Criteria for Diagnosis of Neonatal Sepsis

Iris Streimish
1   Division of Perinatal Medicine, Departments of Pediatrics, Yale University School of Medicine, New Haven, Connecticut
2   Section of Neonatology, Department of Pediatrics, Newton Wellesley Hospital, Special Care Nursery, Newton, Massachusetts
,
Matthew Bizzarro
1   Division of Perinatal Medicine, Departments of Pediatrics, Yale University School of Medicine, New Haven, Connecticut
,
Veronika Northrup
3   Yale Center for Analytical Sciences, New Haven, Connecticut
,
Chao Wang
4   Department of Laboratory Medicine, Yale University School of Medicine, New Haven, Connecticut
,
Sara Renna
1   Division of Perinatal Medicine, Departments of Pediatrics, Yale University School of Medicine, New Haven, Connecticut
,
Nancy Koval
1   Division of Perinatal Medicine, Departments of Pediatrics, Yale University School of Medicine, New Haven, Connecticut
,
Fang-Yong Li
3   Yale Center for Analytical Sciences, New Haven, Connecticut
,
Richard A. Ehrenkranz
1   Division of Perinatal Medicine, Departments of Pediatrics, Yale University School of Medicine, New Haven, Connecticut
,
Henry M. Rinder
4   Department of Laboratory Medicine, Yale University School of Medicine, New Haven, Connecticut
,
Vineet Bhandari
1   Division of Perinatal Medicine, Departments of Pediatrics, Yale University School of Medicine, New Haven, Connecticut
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Weitere Informationen

Publikationsverlauf

21. September 2012

14. Dezember 2012

Publikationsdatum:
01. März 2013 (online)

Abstract

Objective To assess the sensitivity and specificity of neutrophil CD64 as a diagnostic marker for clinical sepsis (based on a hematologic score) and as an additional marker with hematologic parameters for culture-proven sepsis in neonates.

Study Design Prospective observational cohort over 18 months in a single-center neonatal intensive care unit.

Results Hematologic and CD64 data were available on 1,156 sepsis evaluations done in 684 infants, of which 411 (36%) instances of positive clinical sepsis were identified. The CD64 index for clinical sepsis had an overall area under the receiver operating characteristic curve of 0.71. An optimum CD64 cut point value of 2.19 for late-onset clinical sepsis was calculated with a sensitivity of 78%, a specificity of 59%, and a negative predictive value of 81%. The birth weight–specific CD64 cut point for early onset clinical sepsis was 3.13, 2.34, and 2.05 for very low, low, and normal birth weight, respectively. Neutrophil CD64, in combination with the absolute neutrophil count or the absolute band count, had the highest sensitivity (91%) and specificity (93%), respectively, to diagnose culture-proven sepsis.

Conclusion We conclude that neutrophil CD64 index can be incorporated with specific hematologic criteria as an additional marker for diagnosis of neonatal sepsis.

 
  • References

  • 1 Weston EJ, Pondo T, Lewis MM , et al. The burden of invasive early-onset neonatal sepsis in the United States, 2005–2008. Pediatr Infect Dis J 2011; 30: 937-941
  • 2 Stoll BJ, Hansen NI, Sánchez PJ , et al; Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network. Early onset neonatal sepsis: the burden of group B streptococcal and E. coli disease continues. Pediatrics 2011; 127: 817-826
  • 3 Shim GH, Kim SD, Kim HS , et al. Trends in epidemiology of neonatal sepsis in a tertiary center in Korea: a 26-year longitudinal analysis, 1980–2005. J Korean Med Sci 2011; 26: 284-289
  • 4 Tosson AM, Speer CP. Microbial pathogens causative of neonatal sepsis in Arabic countries. J Matern Fetal Neonatal Med 2011; 24: 990-994
  • 5 Baş AY, Demirel N, Zenciroglu A, Göl N, Tanir G. Nosocomial blood stream infections in a neonatal intensive care unit in Ankara, Turkey. Turk J Pediatr 2010; 52: 464-470
  • 6 Mangia CM, Kissoon N, Branchini OA, Andrade MC, Kopelman BI, Carcillo J. Bacterial sepsis in Brazilian children: a trend analysis from 1992 to 2006. PLoS ONE 2011; 6: e14817
  • 7 Schlapbach LJ, Aebischer M, Adams M , et al; Swiss Neonatal Network and Follow-Up Group. Impact of sepsis on neurodevelopmental outcome in a Swiss National Cohort of extremely premature infants. Pediatrics 2011; 128: e348-e357
  • 8 Paolucci M, Landini MP, Sambri V. How can the microbiologist help in diagnosing neonatal sepsis?. Int J Pediatr 2012; 2012: 120139
  • 9 Jardine LA, Sturgess BR, Inglis GD, Davies MW. Neonatal blood cultures: effect of delayed entry into the blood culture machine and bacterial concentration on the time to positive growth in a simulated model. J Paediatr Child Health 2009; 45: 210-214
  • 10 Hashemizadeh Z, Bazargani A, Davarpanah MA. Blood culture contamination in a neonatal intensive care unit in Shiraz, Southwest-Central Iran. Med Princ Pract 2011; 20: 133-136
  • 11 Guerti K, Devos H, Ieven MM, Mahieu LM. Time to positivity of neonatal blood cultures: fast and furious?. J Med Microbiol 2011; 60 (Pt 4) 446-453
  • 12 Benitz WE. Adjunct laboratory tests in the diagnosis of early-onset neonatal sepsis. Clin Perinatol 2010; 37: 421-438
  • 13 Singh SA, Dutta S, Narang A. Predictive clinical scores for diagnosis of late onset neonatal septicemia. J Trop Pediatr 2003; 49: 235-239
  • 14 Manucha V, Rusia U, Sikka M, Faridi MM, Madan N. Utility of haematological parameters and C-reactive protein in the detection of neonatal sepsis. J Paediatr Child Health 2002; 38: 459-464
  • 15 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: 60-68
  • 16 Nigro KG, O'Riordan M, Molloy EJ, Walsh MC, Sandhaus LM. Performance of an automated immature granulocyte count as a predictor of neonatal sepsis. Am J Clin Pathol 2005; 123: 618-624
  • 17 Kudawla M, Dutta S, Narang A. Validation of a clinical score for the diagnosis of late onset neonatal septicemia in babies weighing 1000–2500 g. J Trop Pediatr 2008; 54: 66-69
  • 18 Bhandari V, Wang C, Rinder C, Rinder H. Hematologic profile of sepsis in neonates: neutrophil CD64 as a diagnostic marker. Pediatrics 2008; 121: 129-134
  • 19 Waliullah SM, Islam MN, Siddika M, Hossain MA, Jahan I, Chowdhury AK. Evaluation of simple hematological screen for early diagnosis of neonatal sepsis. Mymensingh Med J 2010; 19: 41-47
  • 20 Selimovic A, Skokic F, Bazardzanovic M, Selimovic Z. The predictive score for early-onset neonatal sepsis. Turk J Pediatr 2010; 52: 139-144
  • 21 Narasimha A, Harendra Kumar ML. Significance of Hematological Scoring System (HSS) in early diagnosis of neonatal sepsis. Indian J Hematol Blood Transfus 2011; 27: 14-17
  • 22 Arnon S, Litmanovitz I, Regev R, Lis M, Shainkin-Kestenbaum R, Dolfin T. The prognostic virtue of inflammatory markers during late-onset sepsis in preterm infants. J Perinat Med 2004; 32: 176-180
  • 23 Ahmed Z, Ghafoor T, Waqar T, Ali S, Aziz S, Mahmud S. Diagnostic value of C- reactive protein and haematological parameters in neonatal sepsis. J Coll Physicians Surg Pak 2005; 15: 152-156
  • 24 Caldas JP, Marba ST, Blotta MH, Calil R, Morais SS, Oliveira RT. Accuracy of white blood cell count, C-reactive protein, interleukin-6 and tumor necrosis factor alpha for diagnosing late neonatal sepsis. J Pediatr (Rio J) 2008; 84: 536-542
  • 25 Bender L, Thaarup J, Varming K, Krarup H, Ellermann-Eriksen S, Ebbesen F. Early and late markers for the detection of early-onset neonatal sepsis. Dan Med Bull 2008; 55: 219-223
  • 26 Khair KB, Rahman MA, Sultana T, Roy CK, Rahman MQ, Ahmed AN. Early diagnosis of neonatal septicemia by hematologic scoring system, C-reactive protein and serum haptoglobin. Mymensingh Med J 2012; 21: 85-92
  • 27 Arnon S, Litmanovitz I, Regev RH, Bauer S, Shainkin-Kestenbaum R, Dolfin T. Serum amyloid A: an early and accurate marker of neonatal early-onset sepsis. J Perinatol 2007; 27: 297-302
  • 28 Cetinkaya M, Ozkan H, Köksal N, Celebi S, Hacimustafaoğlu M. Comparison of serum amyloid A concentrations with those of C-reactive protein and procalcitonin in diagnosis and follow-up of neonatal sepsis in premature infants. J Perinatol 2009; 29: 225-231
  • 29 Mannan MA, Shahidullah M, Noor MK, Islam F, Alo D, Begum NA. Utility of C-reactive protein and hematological parameters in the detection of neonatal sepsis. Mymensingh Med J 2010; 19: 259-263
  • 30 López Sastre JB, Pérez Solís D, Roqués Serradilla V , et al; Grupo de Hospitales Castrillo. Procalcitonin is not sufficiently reliable to be the sole marker of neonatal sepsis of nosocomial origin. BMC Pediatr 2006; 6: 16
  • 31 Naher BS, Mannan MA, Noor K, Shahiddullah M. Role of serum procalcitonin and C-reactive protein in the diagnosis of neonatal sepsis. Bangladesh Med Res Counc Bull 2011; 37: 40-46
  • 32 Fendler WM, Piotrowski AJ. Procalcitonin in the early diagnosis of nosocomial sepsis in preterm neonates. J Paediatr Child Health 2008; 44: 114-118
  • 33 Vouloumanou EK, Plessa E, Karageorgopoulos DE, Mantadakis E, Falagas ME. Serum procalcitonin as a diagnostic marker for neonatal sepsis: a systematic review and meta-analysis. Intensive Care Med 2011; 37: 747-762
  • 34 Ng PC, Li G, Chui KM , et al. Neutrophil CD64 is a sensitive diagnostic marker for early-onset neonatal infection. Pediatr Res 2004; 56: 796-803
  • 35 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: 137-147
  • 36 Choo YK, Cho HS, Seo IB, Lee HS. Comparison of the accuracy of neutrophil CD64 and C-reactive protein as a single test for the early detection of neonatal sepsis. Korean J Pediatr 2012; 55: 11-17
  • 37 Streimish I, Bizzarro M, Northrup V , et al. Neutrophil CD64 as a diagnostic marker in neonatal sepsis. Pediatr Infect Dis J 2012; 31: 777-781
  • 38 Rodwell RL, Leslie AL, Tudehope DI. Early diagnosis of neonatal sepsis using a hematologic scoring system. J Pediatr 1988; 112: 761-767
  • 39 Liu H, Wu HC. Estimating the area under a receiver operating characteristic (ROC) curve for repeated measures design. J Stat Softw 2003; 12: 1-18
  • 40 Ng PC, Lam HS. Biomarkers for late-onset neonatal sepsis: cytokines and beyond. Clin Perinatol 2010; 37: 599-610
  • 41 Mishra UK, Jacobs SE, Doyle LW, Garland SM. Newer approaches to the diagnosis of early onset neonatal sepsis. Arch Dis Child Fetal Neonatal Ed 2006; 91: F208-F212
  • 42 Mahale R, Dutta S, Ahluwalia J, Kishore SS, Narang A. Baseline illness severity does not alter accuracy of neonatal sepsis screen. Am J Perinatol 2010; 27: 327-332
  • 43 Ng PC, Li K, Wong RP, Chui KM, Wong E, Fok TF. Neutrophil CD64 expression: a sensitive diagnostic marker for late-onset nosocomial infection in very low birthweight infants. Pediatr Res 2002; 51: 296-303
  • 44 Ganatra HA, Stoll BJ, Zaidi AK. International perspective on early-onset neonatal sepsis. Clin Perinatol 2010; 37: 501-523
  • 45 Wirtschafter DD, Padilla G, Suh O, Wan K, Trupp D, Fayard EE. Antibiotic use for presumed neonatally acquired infections far exceeds that for central line-associated blood stream infections: an exploratory critique. J Perinatol 2011; 31: 514-518
  • 46 Cotten CM, Taylor S, Stoll B , et al; NICHD Neonatal Research Network. Prolonged duration of initial empirical antibiotic treatment is associated with increased rates of necrotizing enterocolitis and death for extremely low birth weight infants. Pediatrics 2009; 123: 58-66
  • 47 Alexander VN, Northrup V, Bizzarro MJ. Antibiotic exposure in the newborn intensive care unit and the risk of necrotizing enterocolitis. J Pediatr 2011; 159: 392-397
  • 48 Kuppala VS, Meinzen-Derr J, Morrow AL, Schibler KR. Prolonged initial empirical antibiotic treatment is associated with adverse outcomes in premature infants. J Pediatr 2011; 159: 720-725
  • 49 Bizzarro MJ, Gallagher PG. Antibiotic-resistant organisms in the neonatal intensive care unit. Semin Perinatol 2007; 31: 26-32
  • 50 Couto RC, Barbosa JA, Pedrosa TM, Biscione FM. C-reactive protein-guided approach may shorten length of antimicrobial treatment of culture-proven late-onset sepsis: an intervention study. Braz J Infect Dis 2007; 11: 240-245
  • 51 Cantey JB, Sánchez PJ. Prolonged antibiotic therapy for “culture-negative” sepsis in preterm infants: it's time to stop!. J Pediatr 2011; 159: 707-708
  • 52 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: 254-259
  • 53 Buhimschi CS, Bhandari V, Hamar BD , et al. Proteomic profiling of the amniotic fluid to detect inflammation, infection, and neonatal sepsis. PLoS Med 2007; 4: e18
  • 54 Buhimschi CS, Buhimschi IA, Abdel-Razeq S , et al. Proteomic biomarkers of intra-amniotic inflammation: relationship with funisitis and early-onset sepsis in the premature neonate. Pediatr Res 2007; 61: 318-324
  • 55 Dulay AT, Buhimschi IA, Zhao G , et al. Nucleated red blood cells are a direct response to mediators of inflammation in newborns with early-onset neonatal sepsis. Am J Obstet Gynecol 2008; 198: e1-e9
  • 56 Buhimschi CS, Abdel-Razeq S, Cackovic M , et al. Fetal heart rate monitoring patterns in women with amniotic fluid proteomic profiles indicative of inflammation. Am J Perinatol 2008; 25: 359-372
  • 57 Buhimschi CS, Bhandari V, Dulay AT , et al. Proteomics mapping of cord blood identifies haptoglobin “switch-on” pattern as biomarker of early-onset neonatal sepsis in preterm newborns. PLoS ONE 2011; 6: e26111
  • 58 Hornik CP, Benjamin DK, Becker KC , et al. Use of the complete blood cell count in early-onset neonatal sepsis. Pediatr Infect Dis J 2012; 31: 799-802
  • 59 Hornik CP, Benjamin DK, Becker KC , et al. Use of the complete blood cell count in late-onset neonatal sepsis. Pediatr Infect Dis J 2012; 31: 803-807
  • 60 Christensen RD, Rothstein G. Pitfalls in the interpretation of leukocyte counts of newborn infants. Am J Clin Pathol 1979; 72: 608-611