IMPORTANCE Infection in neonates remains a substantial problem. Advances for this population are hindered by the absence of a consensus definition for sepsis. In adults, the Sequential Organ Failure Assessment (SOFA) operationalizes mortality risk with infection and defines sepsis. The generalizability of the neonatal SOFA (nSOFA) for neonatal late-onset infection-related mortality remains unknown. OBJECTIVE To determine the generalizability of the nSOFA for neonatal late-onset infection-related mortality across multiple sites.

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These data highlight the potential of biosignatures in the host's CSF for diagnostic applications and for improving our understanding of the pathogenesis of TBM to discover strategies to prevent immunopathological sequelae.

Background Early diagnosis of bacterial sepsis in neonates is hampered by non-specific symptoms and the lack of rapid responding laboratory measures. The biomarker soluble CD14 subtype (sCD14-ST) seems promising in the diagnostic process of neonatal sepsis. In order to evaluate the differences in diagnostic accuracy of sCD14-ST between early onset sepsis (EOS) and late onset sepsis (LOS) we assessed this systematic review and meta-analysis. Results Twelve articles were included in the systematic review and 10 in the meta-analysis. There was a high risk of bias on patient selection, index test and/or flow and timing. The overall quality of the included studies was moderate. At sepsis onset a consequently higher level of sCD14-ST was found in septic neonates compared to healthy controls with significant higher levels in LOS compared to EOS. In the first 24 h after sepsis onset a significant increase in pooled means of plasma sCD14-ST levels was seen in EOS (t(71.6) = 7.3, p < .0001) while this was not seen in LOS or healthy controls. Optimal cut-off values ranged from 305 to 672 ng/l for EOS cases versus healthy controls. The pooled sensitivity was 81% (95%CI: 0.76–0.85), the pooled specificity was 86% (0.81–0.89) with an AUC of 0.9412 (SE 0.1178). In LOS optimal cut-off values ranged from 801 to 885 ng/l with a pooled sensitivity of 81% (0.74–0.86) and a pooled specificity of 100% (0.98–1.00). An AUC and SROC was not estimable in LOS because of the low number of studies. Conclusions sCD14-ST is a promising and rapid-responding diagnostic biomarker for EOS and LOS. The difference in pooled means between EOS and LOS underlines the importance to consider EOS and LOS as two different disease entities, requiring separate analysis in original articles and systematic reviews. Electronic supplementary material The online version of this article (10.1186/s12865-019-0298-8) contains supplementary material, which is available to authorized users.

Although commercial nucleic-acid amplification tests performed on CSF revealed incrementally improved diagnostic accuracy, providing rapid microbiological confirmation, they cannot serve as a rule-out test.

Multidrug-resistant TBM in children has poor clinical outcome and is associated with death. We did not find any difference in the outcomes between children with isoniazid monoresistant TBM and those with drug-susceptible TBM. One explanation could be the local treatment regimen. Further investigation of this regimen is indicated.

Absolute CSF glucose values of <2.2 mmol/L and protein values of >1 g/L differentiated between TBM and non-bacterial meningitis with good specificity, although sensitivity was poor. A CSF to serum glucose ratio is more informative than the absolute value.

The neonatal early onset sepsis (EOS) calculator is a novel tool for antibiotic stewardship in newborns, associated with a reduction of empiric antibiotic treatment for suspected EOS. We studied if implementation of the EOS calculator results in less healthcare utilization and lower financial costs of suspected EOS. For this, we compared two single-year cohorts of hospitalizations within 3 days after birth in a Dutch nonacademic teaching hospital, before and after implementation of the EOS calculator. All admitted newborns born at or after 35 weeks of gestation were eligible for inclusion. We analyzed data from 881 newborns pre-implementation and 827 newborns post-implementation. We found significant reductions in EOS-related laboratory tests performed and antibiotic days, associated with implementation of the EOS calculator. Mean length of hospital stay was shorter, and EOS-related financial costs were lower after implementation among term, but not among preterm newborns.Conclusion: In addition to the well-known positive impact on antibiotic stewardship, implementation of the EOS calculator is also clearly associated with reductions in healthcare utilization related to suspected EOS in late preterm and term newborns and with a reduction in associated financial costs among those born term.What is Known: • The early-onset sepsis (EOS) calculator is a novel tool for antibiotic stewardship in newborns, associated with a reduction in empiric antibiotic treatment for suspected EOS. What is New:• In newborns at risk for EOS, EOS calculator implementation is associated with a significant reduction in laboratory investigations related to suspected EOS and significantly shorter stay in those born term. • EOS calculator implementation in term newborns is associated with a mean reduction of €207 in costs for EOS-related care per admitted newborn.