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Diagnostic Performance of Triggering Receptor Expressed on Myeloid Cells-1 and CD64 Index as Markers of Sepsis in Preterm Newborns

Mazzucchelli, Iolanda PhD1,2; Garofoli, Francesca PhD1; Ciardelli, Laura PhD3; Borghesi, Alessandro MD4; Tzialla, Chryssoulla MD4; Di Comite, Amelia MD4; Angelini, Micol PhD1; Tinelli, Carmine MD5; Merlini, Giampaolo MD3; Stronati, Mauro MD4

Pediatric Critical Care Medicine:
doi: 10.1097/PCC.0b013e31826e726d
Neonatal Intensive Care
Abstract

Objective: CD64 index and triggering receptor expressed on myeloid cells-1 are biomarkers on neutrophil polymorphonuclear cells with crucial role in sepsis. The study aim is to assess diagnostic performance, individually and combined, of CD64 index and triggering receptor expressed on myeloid cells-1 (surface marker/soluble form), in late-onset sepsis of preterm infants.

Design: Observational study.

Setting: Neonatal ICU.

Patients: Sixteen septic and 16 control preterm infants, gestational age younger than 32 weeks and/or birth weigh less than 1500 g.

Measurement and Main Results: Seventy preterm infants, free of sepsis were enrolled into the study. CD64 index and triggering receptor expressed on myeloid cells-1 were measured once between day 5 and 15 of life (T0) and once between day 16 and 25 (T1). At T1, 16 infants were assigned to septic group because of reported signs of sepsis and positive blood culture. From the remaining 54 infants, 16 of them who always remained free of sepsis had a blood sample at T1 and constituted the control group (n = 16). Comparing T1 vs T0, triggering receptor expressed on myeloid cells-1 polymorphonuclear cells percentage was significantly lower (p = 0.002) in septic group but not in control group; soluble triggering receptor expressed on myeloid cells-1 concentration did not show significant differences in both groups; CD64 index significantly increased (p = 0.0004) in septic group, while no difference was found in control group. Comparing septic with control group at T0, no differences were found in any markers. At T1, triggering receptor expressed on myeloid cells-1 polymorphonuclear cells percentage was significantly lower (p = 0.003) and CD64 index was higher (p = 0.00019) in septic infants. Triggering receptor expressed on myeloid cells-1 polymorphonuclear cells receiver operating characteristic curve indicated cutoff 62.12%, sensitivity 56.2%, specificity 93.5%, and area under the curve 0.8. CD64 index receiver operating characteristic curve indicated cutoff 2.85, sensitivity 87.5%, specificity 100%, and area under the curve 0.95. Combination of the two indexes was not useful in increasing individual diagnostic power.

Conclusions: Despite limited sample size, CD64 index demonstrated to be a promising biomarker, with high specificity, to diagnose late-onset sepsis. Further investigations are needed to substantiate these findings. Triggering receptor expressed on myeloid cells-1 showed less valuable diagnostic role.

Author Information

1 Laboratory of Neonatal Immunology, Neonatal Intensive Care Unit, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy.

2 Department of Internal Medicine and Therapeutics, University of Pavia, Italy.

3 Clinical Chemistry Laboratories, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy.

4 Neonatal Unit and Neonatal Intensive Care Unit, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy.

5 Biometric Unit, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy.

Drs. Mazzucchelli and Garofoli contributed equally to the study.

The authors declare that the article is not under consideration elsewhere, none of the article’s contents have been previously published, they have no commercial association (e.g., consultancies, stock ownership, equity interest, patent/licensing, arrangements) that may pose a conflict of interest in connection with the submitted article, moreover, they have no competing interest, no industry relationship, no study sponsor, and received no funding for this work from any organizations. The study comply with the Declaration of Helsinki and the study was approved by the Bioethic Committee of the Fondazione IRCCS Policlinico San Matteo, Pavia, Italy, written informed consent was obtained from all parents before the enrolment. They have seen and approved the content and have contributed significantly to the work.

For information regarding this article, E-mail: lab.immunoneo@smatteo.pv.it

©2013The Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies