Soluble CD14 subtype (sCD14-ST) as biomarker in neonatal early-onset sepsis and late-onset sepsis: a systematic review and meta-analysis

Abstract

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.

Inflammation and Premature Ageing in Chronic Kidney Disease

“…Possible exposure to bacterial endotoxin, which activates the immune system and contributes to systemic inflammation, can furthermore result from comorbidities, such as gingivitis and periodontitis [17]. Patients with CKD may also show signs of intestinal dysbiosis and increased gut permeability [10], which lead to the presence of bacterial DNA and elevated endotoxin levels, as well as elevated plasma levels of the macrophage-derived cluster of differentiation (CD)14 [10], a co-receptor in the recognition of bacterial endotoxin [18].…”

Relevance of Biomarkers Currently in Use or Research for Practical Diagnosis Approach of Neonatal Early-Onset Sepsis

“…Presepsin, a cleaved truncated form of soluble CD14 (sCD14), is a surface glycoprotein with a high affinity for lipopolysaccharides, and according to recent studies, it may be a better marker than CRP and PCT for the diagnosis of EOS [ 92 ]. sCD14 level not only increases in the first 24 h after the onset of infection, just before CRP and PCT, but also has a higher area under the curve (AUC, 0.97–0.99), being considered an efficient marker in diagnosing EOS [ 33 , 91 , 93 , 94 ]. In a newborn without signs of infection, the mean value of presepsin differs in term (649 ng/L) compared to premature infants (720 ng/L) [ 95 ].…”

Biomarkers for Point-of-Care Diagnosis of Sepsis

“…The lack of a pre-specified diagnostic cut-off is also apparent with presepsin, with both the meta-analyses led by Bellos [78] and Kondo [65] in neonatal and adult populations, respectively, limited due to many studies lacking such pre-specified cut-off values, which increases the risk of bias in these studies. In neonatal populations, Bellos and co-workers [78] stratified cut-off values into ≤650, 650 to 850 and ≥850pg/mL, while van Maldeghem and co-workers [82] noted a range of between 305 and 885pg/mL in the studies analysed. In older children, Yoon and co-workers [85] noted a range of cut-offs from 240 to 1014pg/mL, with higher diagnostic accuracy achieved at values greater than 650pg/mL.…”

“…It is possible that early-and late-onset sepsis should be considered separate entities when investigating possible diagnostic approaches. The differences between early-and late-onset sepsis and the use of presepsin was investigated in a meta-analysis of 10 studies by van Maldeghem and co-workers [82], who calculated an AUC of 0.9412 for diagnosis in early-onset sepsis. Unfortunately they were unable to calculate an AUC for late-onset sepsis due to a lack of data on this population, although by combining all data they were able to calculate an overall AUC 0f 0.9639 for neonatal sepsis as a whole.…”