Diagnosis of late onset neonatal sepsis with cytokines, adhesion molecule, and C-reactive protein in preterm very low birthweight infants

Abstract

Aims-To evaluate the commonly used markers-namely IL-6, TNF , IL-1 , C-reactive protein and E-selectin for identification of late onset neonatal sepsis; to define the optimal cutoV value for each marker in preterm neonates; to assess whether these markers could assist in early discontinuation of antibiotics in non-infected cases; and to delineate the profile of these markers during systemic infection and in relation to successful treatment. Methods-Very low birthweight infants in whom clinical sepsis was suspected when they were >72 hours of age were eligible for study. A full sepsis screen was performed in each episode. Cytokines, C-reactive protein, and E-selectin were serially measured on days 0 (at the time of sepsis evaluation), 1, 2, 4 and 7. The optimal cutoV value for each marker was calculated after minimising the number of misclassified episodes over all possible cutoV values for days 0 and 1. The sensitivity, specificity, positive and negative predictive values for each test and combination of tests for predicting systemic infection were also determined. Results-One hundred and one episodes of suspected clinical sepsis were investigated in 68 infants. Forty five episodes were proved to be infections. The optimal cutoV values were IL-6 31 pg/ml, TNF 17 pg/ml, IL-1 1 pg/ml, C reactive protein 12 mg/l and E-selectin 174 ng/ml. IL-6 had the highest sensitivity (89%) and negative predictive value (91%) for detecting late onset infection on day 0. However, between 24 and 48 hours of onset, C-reactive protein was the best single marker, with an overall sensitivity and specificity of 84% and 96%, respectively. The use of serial and multiple markers in the first 48 hours further enhanced the sensitivity and specificity of these tests. Performing IL-6 and C-reactive protein on day 0, together with either TNF on day 1 or C-reactive protein on day 2, showed the best overall sensitivity (98%) and specificity (91%) for the diagnosis of late onset infection. Conclusions-Optimal cutoV values for these markers in detecting late onset systemic infection in very low birthweight infants have been defined. Withholding antibiotic treatment at the onset of infection could be fatal and is not recommended, but the concomitant use of IL-6 and C-reactive protein or TNF should allow antimicrobial treatment to be discontinued at 48 hours without waiting for microbiological results, provided that the infants are in good clinical condition.

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

“…Although the initial clinical signs and symptoms are subtle, the clinical course can rapidly progress and worsen, and may lead to disseminated intravascular coagulation and death within hours. 2,20 Also, noninfected infants such as those with transient tachypnea of the newborn, meconium aspiration syndrome, respiratory distress syndrome, apnea of prematurity and acute exacerbation of chronic lung disease are often clinically indistinguishable from infants who are really in the initial stages of bacterial infection. 21 If the absence Abbreviations: AUC, area under the curve; CI, confidence interval; CRP, C-reactive protein; NPV, negative predictive value; PCT, procalcitonin; PPV, positive predictive value; SAA, serum amyloid A.…”

Comparable effect of conventional ventilation versus early high-frequency oscillation on serum CC16 and IL-6 levels in preterm neonates

“…6 Moreover, in a model of neonatal lung injury, IL-6 in tracheal aspirates was significantly higher in the HFOV-treated animals only at 24 h of age but not during the following 28 days. 3 Systemic inflammatory response either in the fetus (chorioamnionitis) 28 or in the neonate (nosocomial sepsis) 31 influences circulating IL-6 greatly. In this study, subclinical chorioamnionitis cannot be ruled out, but comparable IL-6 levels are suggestive of a similar baseline inflammation in both groups.…”

Flow cytometric methods for prenatal and neonatal diagnosis

“…A reliable marker of infection or a set of markers that can quickly and accurately diagnose these infections using small volumes of peripheral blood could lead to faster, more effective treatment. A variety of biomarkers have been studied that include hematologic parameters such as immature/total neutrophil ratio (Rodwell et al, 1988 andBerger et al, 1995), C-reactive protein (Berger et al, 1995;Ng et al, 1997;Wagle et al, 1994;and Hatherill et al, 1999), procalcitonin (Hatherill et al, 1999;Gendrel et al, 1996), TNF-α (Ng et al, 1997), IL-1β (Ng et al, 1997), soluble IL-1ra (Küster et al, 1998), IL-2 receptor (Jurges and Henderson, 1996), IL-6 (Ng et al, 1997 andKüster et al, 1998), IL-8 (Franz et al, 1999 andBerner et al, 2000), IL-10 (van der Poll et al, 1997) and markers of complement activation (Zilow et al, 1993). Each of these markers offers some utility to the clinician during acute care of the infant, but they have yet to become a routine test for care of acutely ill infants in most settings.…”