The Diagnostic Performance of Interleukin-6 and C-Reactive Protein for Early Identification of Neonatal Sepsis

Abstract

Interleukin-6 (IL-6) and C-reactive protein (CRP) are being used for diagnosis of sepsis. However, studies have reported varying cut-off levels and diagnostic performance. This study aims to investigate the optimal cut-off levels and performance of IL-6 and CRP for the diagnosis of neonatal sepsis. The study was conducted at the University Hospital of Leipzig, Germany from November 2012 to June 2020. A total of 899 neonates: 104 culture proven sepsis, 160 clinical sepsis, and 625 controls were included. Blood culture was performed using BacT/ALERT 3D system. IL-6 and CRP were analyzed by electrochemiluminescent immunoassay and immunoturbidimetric assay, respectively. Data were analyzed using SPSS 20 statistical software. Among neonates with proven sepsis, the optimal cut-off value of IL-6 was 313.5 pg/mL. The optimal cut-off values for CRP in 5 days serial measurements (CRP1, CRP2, CRP3, CRP4, and CRP5) were 2.15 mg/L, 8.01 mg/L, 6.80 mg/L, 5.25 mg/L, and 3.72 mg/L, respectively. IL-6 showed 73.1% sensitivity, 80.2% specificity, 37.6% PPV, and 94.8% NPV. The highest performance of CRP was observed in the second day with 89.4% sensitivity, 97.3% specificity, 94.5% PPV, and 98.3% NPV. The combination of IL-6 and CRP showed increase in sensitivity with decrease in specificity. In conclusion, this study defines the optimal cut-off values for IL-6 and CRP. The combination of IL-6 and CRP demonstrated increased sensitivity. The CRP 2 at cut-off 8.01 mg/L showed the highest diagnostic performance for identification of culture negative clinical sepsis cases. We recommend the combination of IL-6 (≥313.5 pg/mL) and CRP1 (≥2.15 mg/L) or IL-6 (≥313.5 pg/mL) and CRP2 (≥8.01 mg/L) for early and accurate diagnosis of neonatal sepsis. The recommendation is based on increased sensitivity, that is, to minimize the risk of any missing cases of sepsis. The CRP2 alone at cut-off 8.01 mg/L might be used to identify clinical sepsis cases among culture negative sepsis suspected neonates in hospital settings.

Antibiotic Resistance Patterns of Bacterial Isolates from Neonatal Sepsis Patients at University Hospital of Leipzig, Germany

“…Newborns with positive blood cultures for CoNS organisms and low CRP concentrations, <10 mg/L were considered as potential contamination and omitted from our final analysis. Newborns were grouped as EOS cases when sepsis onset is in ≤72 h of newborns after birth, or LOS cases when sepsis onset is >72 h of newborns after birth [ 47 ].…”

“…From sepsis-suspected neonate, blood sample was collected and cultured using automated BacT/ALERT 3D system, a positive culture was sub-cultured, as described in our previously published work [ 47 ]. Pure colonies of bacteria or yeasts isolated from the blood culture were characterized to the species level with Vitek matrix-assisted laser desorption ionization time-of-flight (MALDI-TOF) mass spectrometry (BioMérieux, Marcy L’Etoile, France).…”

Comparison of Two Predictive Models of Sepsis in Critically Ill Patients Based on the Combined use of Inflammatory Markers

“…Sepsis is induced by infection, involving complex in ammatory responses during its progress, which is accompanied by pro-in ammatory and anti-in ammatory mechanisms [8,9]. Conventional in ammatory markers, such as procalcitonin (PCT), interleukin-6 (IL-6), white blood cell (WBC), and C-reactive protein (CRP), may be served as potential markers to help clinicians identify sepsis early [10][11][12][13][14]. Neutrophil-tolymphocyte ratio (NLR), an easily accessible biomarker that can be calculated from components of the differential white cell count (dividing neutrophil by lymphocyte count), has shown good predictive and prognostic performance in various disease [15][16][17][18].…”

The Potential Value of Plasma Receptor Interacting Protein 3 for Neonatal Sepsis Diagnosis

“…The early diagnosis of neonatal sepsis is challenging because its clinical features are highly variable and may be confused with non-infectious disorders [4,5] . Missed identification and delayed treatment can rapidly lead to multiple organ dysfunctions [6][7][8] . Moreover, some survivors of neonatal sepsis may have behavioral and neurocognitive dysfunction, mood disorders, and a low quality of life, which causes a huge burden to the medical system and society [2,9] .…”