Biomarkers of Neonatal Sepsis: Where We Are and Where We Are Going

Abstract

Neonatal sepsis is a bacterial bloodstream infection leading to severe clinical manifestations frequently associated with death or irreversible long-term deficits. Antibiotics are the drug of choice to treat sepsis, regardless of age. In neonates, the lack of reliable criteria for a definite diagnosis and the supposition that an early antibiotic administration could reduce sepsis development in children at risk have led to a relevant antibiotic overuse for both prevention and therapy. The availability of biomarkers of neonatal sepsis that could alert the physician to an early diagnosis of neonatal sepsis could improve the short and long-term outcomes of true sepsis cases and reduce the indiscriminate and deleterious use of preventive antibiotics. The main aim of this narrative review is to summarize the main results in this regard and to detail the accuracy of currently used biomarkers for the early diagnosis of neonatal sepsis. Literature analysis showed that, despite intense research, the diagnosis of neonatal sepsis and the conduct of antibiotic therapy cannot be at present decided on the basis of a single biomarker. Given the importance of the problem and the need to reduce the abuse of antibiotics, further studies are urgently required. However, instead of looking for new biomarkers, it seems easier and more productive to test combinations of two or more of the presently available biomarkers. Moreover, studies based on omics technologies should be strongly boosted. However, while waiting for new information, the use of the clinical scores prepared by some scientific institutions could be suggested. Based on maternal risk factors and infant clinical indicators, sepsis risk can be calculated, and a significant reduction in antibiotic consumption can be obtained.

Enhancing Early Detection of Sepsis in Neonates through Multimodal Biosignal Integration: A Study of Pulse Oximetry, Near-Infrared Spectroscopy (NIRS), and Skin Temperature Monitoring

“…Although our findings seem promising, C-reactive protein (CRP), procalcitonin (PCT), and white blood cell count provide essential information about the inflammatory response and the likelihood of sepsis, while blood cultures remain the gold standard for confirming bacterial infections by offering definitive evidence of the causative pathogens [23]. However, these methods can be limited by the time required to obtain results and the potential for false negatives, especially in cases of early or low-grade infections.…”

An Overview of Antibiotic Therapy for Early- and Late-Onset Neonatal Sepsis: Current Strategies and Future Prospects

“…Despite blood culture still being considered the gold standard for diagnosis, it has several limitations and needs from 2 to 7 days for the laboratory results to be retrieved. Unfortunately, none of the studied biomarkers that have been proposed fulfill all the criteria for becoming an ideal marker [ 15 ].…”

“…Blood culture is the gold standard for diagnosis, but has several limitations, mainly the low sensitivity and the long turnaround time that contribute to inappropriate antibiotic therapy [ 13 ]. Nonculture-based techniques, including molecular methods and mass spectrometry, may overcome some of the limitations seen with culture-based techniques [ 14 , 15 ]. Biomarkers, including hematological indices, cell adhesion molecules, interleukins, and acute-phase reactants, have been used for the diagnosis of neonatal sepsis [ 14 , 15 ].…”

“…Nonculture-based techniques, including molecular methods and mass spectrometry, may overcome some of the limitations seen with culture-based techniques [ 14 , 15 ]. Biomarkers, including hematological indices, cell adhesion molecules, interleukins, and acute-phase reactants, have been used for the diagnosis of neonatal sepsis [ 14 , 15 ]. However, the search for an ideal biomarker that has adequate diagnostic accuracy early on is still ongoing [ 14 , 15 ].…”

“…Biomarkers, including hematological indices, cell adhesion molecules, interleukins, and acute-phase reactants, have been used for the diagnosis of neonatal sepsis [ 14 , 15 ]. However, the search for an ideal biomarker that has adequate diagnostic accuracy early on is still ongoing [ 14 , 15 ]. Thus, all neonates at risk of infection, including preterm infants, are treated with large-spectrum empirical antibiotics, even in the absence of a clinical manifestation [ 16 ].…”