Title NMR-based metabolic profiling provides diagnostic and prognostic information in critically ill children with suspected infection.

Sepsis, defined as life-threatening organ dysfunction caused by infection is difficult to distinguish clinically from infection or post-operative inflammation. We hypothesized that in a heterogeneous group of critically ill children, there would be different metabolic profiles between post-operative inflammation, bacterial and viral infection and infection with or without organ dysfunction. 1D 1H nuclear magnetic resonance spectra were acquired in plasma samples from critically ill children. We included children with bacterial (n = 25) and viral infection (n = 30) and controls (n = 58) (elective cardiac surgery without infection). Principal component analysis was used for data exploration and partial least squares discriminant analysis models for the differences between groups. Area under receiver operating characteristic curve (AUC) values were used to evaluate the models. Univariate analysis demonstrated differences between controls and bacterial and viral infection. There was excellent discrimination between bacterial and control (AUC = 0.94), and viral and control (AUC = 0.83), with slightly more modest discrimination between bacterial and viral (AUC = 0.78). There was modest discrimination (AUC = 0.73) between sepsis with organ dysfunction and infection with no organ dysfunction. In critically ill children, NMR metabolomics differentiates well between those with a post-operative inflammation but no infection, and those with infection (bacterial and viral), and between sepsis and infection.

Bloodstream infections in pediatric ECLS: usefulness of daily blood culture monitoring and predictive value of biological markers. The British Columbia experience.

INTRODUCTION: The incidence of bloodstream infection (BSI) in extracorporeal life support (ECLS) is reported between 0.9 and 19.5%. In January 2006, the Extracorporeal Life Support Organization (ELSO) reported an overall incidence of 8.78% distributed as follows: respiratory: 6.5% (neonatal), 20.8% (pediatric); cardiac: 8.2% (neonatal) and 12.6% (pediatric). METHOD: At BC Children's Hospital (BCCH) daily surveillance blood cultures (BC) are performed and antibiotic prophylaxis is not routinely recommended. Positive BC (BC+) were reviewed, including resistance profiles, collection time of BC+, time to positivity and mortality. White blood cell count, absolute neutrophile count, immature/total ratio, platelet count, fibrinogen and lactate were analyzed 48, 24 and 0 h prior to BSI. A univariate linear regression analysis was performed. RESULTS: From 1999 to 2005, 89 patients underwent ECLS. After exclusion, 84 patients were reviewed. The attack rate was 22.6% (19 BSI) and 13.1% after exclusion of coagulase-negative staphylococci (n = 8). BSI patients were significantly longer on ECLS (157 h) compared to the no-BSI group (127 h, 95% CI: 106-148). Six BSI patients died on ECLS (35%; 4 congenital diaphragmatic hernias, 1 hypoplastic left heart syndrome and 1 after a tetralogy repair). BCCH survival on ECLS was 71 and 58% at discharge, which is comparable to previous reports. No patient died primarily because of BSI. No BSI predictor was identified, although lactate may show a decreasing trend before BSI (P = 0.102). CONCLUSION: Compared with ELSO, the studied BSI incidence was higher with a comparable mortality. We speculate that our BSI rate is explained by underreporting of "contaminants" in the literature, the use of broad-spectrum antibiotic prophylaxis and a higher yield with daily monitoring BC. We support daily surveillance blood cultures as an alternative to antibiotic prophylaxis in the management of patients on ECLS.

Common human Toll-like receptor 4 polymorphisms--role in susceptibility to respiratory syncytial virus infection and functional immunological relevance.

Evidence suggests that Toll-like receptor 4 (TLR4) contributes to immune recognition of respiratory syncytial virus (RSV). The TLR4 gene harbours a polymorphism-Asp299Gly-previously associated with reduced TLR4 signalling. To understand of how host genetic variation influences the outcome of RSV infection in children, we examined the association between the TLR4 299Gly allele and severe RSV disease. By genotyping 236 children with RSV infection and 219 healthy controls we found no association between the risk of severe RSV infection and Asp299Gly polymorphisms (P>0.05), and we demonstrate that the TLR4 Asp299Gly genotype does not influence susceptibility to either RSV serotype A or B (P>0.05). Finally, examining the functional impact of the TLR4 Asp299Gly polymorphism (n=58), we demonstrate that proinflammatory cytokine production following TLR4 activation was indistinguishable between homozygous (Asp/Asp) and heterozygous (Asp/Gly) subjects. We conclude that the Asp299Gly TLR4 polymorphism does not alter receptor function and does not influence the risk of severe RSV infection.