Diagnosis of neonatal sepsis: the past, present and future

Abstract

Sepsis remains a significant cause of neonatal mortality and morbidity, especially in low- and middle-income countries. Neonatal sepsis presents with nonspecific signs and symptoms that necessitate tests to confirm the diagnosis. Early and accurate diagnosis of infection will improve clinical outcomes and decrease the overuse of antibiotics. Current diagnostic methods rely on conventional culture methods, which is time-consuming, and may delay critical therapeutic decisions. Nonculture-based techniques including molecular methods and mass spectrometry may overcome some of the limitations seen with culture-based techniques. Biomarkers including hematological indices, cell adhesion molecules, interleukins, and acute-phase reactants have been used for the diagnosis of neonatal sepsis. In this review, we examine past and current microbiological techniques, hematological indices, and inflammatory biomarkers that may aid sepsis diagnosis. The search for an ideal biomarker that has adequate diagnostic accuracy early in sepsis is still ongoing. We discuss promising strategies for the future that are being developed and tested that may help us diagnose sepsis early and improve clinical outcomes. IMPACT: Reviews the clinical relevance of currently available diagnostic tests for sepsis. Summarizes the diagnostic accuracy of novel biomarkers for neonatal sepsis. Outlines future strategies including the use of omics technology, personalized medicine, and point of care tests.

Figure 1:. A Schematic on the categories of diagnostic tests available for neonatal sepsis

Traditional methods of blood cultures have changed to automated blood culture monitoring for bacterial growth by CO2 detection. Newer tests involve rapidly identifying organisms from positive cultures by fluorescent in situ hybridization techniques. Molecular microbiological diagnostics using PCR for bacterial and fungal genes can be applied directly to blood specimens. Inflammatory biomarkers including CRP, procalcitonin and cytokines are another category of adjunctive diagnostic tests. Multiomic technology enables us to scour genome wide gene expression, protein and metabolites for developing diagnostic tests and prognostic models.

Figure 2.. The relationship between host immunity and biomarkers

CD, cluster of differentiation; sTREM-1, soluble triggering receptor expressed on myeloid cells-1; ICAM, intracellular adhesion molecule; VCAM, vascular cell adhesion molecule; RNA, ribonucleic acid; DNA, deoxyribonucleic acid; DAMPs, damage associated molecular patterns; HGM-1, high mobility group box 1; LPS, lipopolysaccharide,; LTA, lipoteichoic acid; NETs, neutrophil extracellular traps; TLR, toll-like receptor; HSP, Heat shock protein; TNF-α, tumor necrosis factor-α; INF-γ, interferon-γ; IL, interleukin; MCP-1, monocyte chemoattractant protein-1; CXCL-10, chemokine ligand-10

Figure 3.. Point of care testing for diagnosis of neonatal sepsis

Blood samples are drawn on suspicion of infection on laboratory chips that are microbiology, immune, or molecular based diagnostics. The results enable us to initiate targeted therapy. The rapid results and targeted therapy will improve clinical outcomes.