Early Inflammatory Markers for the Diagnosis of Late-Onset Sepsis in Neonates: The Nosodiag Study

Abstract

Background: Early diagnosis is essential to improve the treatment and prognosis of newborn infants with nosocomial bacterial infections. Although cytokines and procalcitonin (PCT) have been evaluated as early inflammatory markers, their diagnostic properties have rarely been compared.Objectives: This study evaluated and compared the ability of individual inflammatory markers available for clinician (PCT, semi-quantitative determination of IL-8) and of combinations of markers (CRPi plus IL-6 or quantitative or semi-quantitative determination of IL-8) to diagnose bacterial nosocomial infections in neonates.Methods: This prospective two-center study included neonates suspected of nosocomial infections from September 2008 to January 2012. Inflammatory markers were measured initially upon suspicion of nosocomial infection, and CRP was again measured 12–24 h later. Newborns were retrospectively classified into two groups: those who were infected (certainly or probably) and uninfected (certainly or probably).Results: The study included 130 infants of median gestational age 28 weeks (range, 24–41 weeks). Of these, 34 were classified as infected and 96 as uninfected. The sensitivity, specificity, positive and negative predictive values (PPV and NPV), and positive and negative likelihood ratios (LR+ and LR-) for PCT were 59.3% (95% confidence interval [CI], 38.8–77.6%), 78.5% (95% CI, 67.8–86.9%), 48.5% (95% CI, 30.8–66.5%), 84.9% (95% CI, 74.6–92.2%), 2.7 (95% CI, 1.6–4.9), and 0.5 (95% CI, 0.3–0.8), respectively. Semi-quantitative IL-8 had the highest specificity (92.19%; 95% CI, 82.70–97.41%), PPV (72.22%; 95% CI, 46.52–90.30%) and LR+ (6.17, 95% CI, 2.67–28.44), but had low specificity (48.15%; 95% CI, 28.67–68.05%). Of all markers tested, the combination of IL-6 and CRPi had the highest sensitivity (78.12%; 95% CI, 60.03–90.72%), NPV (91.3%; 95% CI, 82.38–96.32%) and LR- (0.29; 95% CI, 0.12–0.49). The combination of IL-6 and CRPi had a higher area under the curve than PCT, but with borderline significance (p = 0.055).Conclusions: The combination of IL-6 and CRPi was superior to other methods, including PCT, for the early diagnosis of nosocomial infection in neonates, but was not sufficient for sole use. The semi-quantitative determination of IL-8 had good diagnostic properties but its sensitivity was too low for use in clinical practice.

Clinical and Microbiological Features of Early-Onset Neonatal Sepsis in Preterm Infants

“…The low level of bacteremia, as well as the insufficient volume taken for blood tests, especially in children with extremely low body weight, may be one of the explanations for a large number of cases of culture-negative sepsis. In addition, antibiotic treatment in the mother before or during childbirth may in some cases mask the detection of bacteremia in the newborn [15]. In cases where the blood cultures and other sterile cultures are negative, but the child shows signs that correspond to the implementation of the infectious process, they can be considered "clinical" sepsis [16].…”

Dynamic changes and clinical significance of LXA4 in the perioperative period of cardiopulmonary bypass

“…In this study, it was also found that WBC, N% and hs-CRP were transiently increased at T0 and were most significantly increased at T1, which is consistent with the results of a number of experiments ( 14 , 15 ). CRP is an acute-phase reactive protein and an important inflammatory marker, which will obviously increase in the case of acute inflammation and trauma in the body ( 16 ). With the application of anti-inflammatory and anti-infective drugs after operation and inflammation control, CRP gradually declines, and the body temperature also gradually drops to normal.…”

Protective effect of Apelin/APJ system on lipopolysaccharide-related cardiac dysfunction

“…TNF-α increased sharply after the injection of LPS, followed by the increase of IL-6, while TNF-α decreased rapidly in vivo (Michie et al 1988;Fong and Lowry 1990). However, the level of IL-6 in plasma is considered to be more valuable for the prediction of mortality (Sullivan et al 1992) and nosocomial infection (Dillenseger et al 2018). Kumar et al (1999) found that TNF-α, IL-6 and other inflammatory factors had inhibitory effect on the contraction of cardiomyocytes, which was positively correlated with the dose.…”