Sepsis Biomarkers In Early Onset Neonatal Infections: A Review

摘要

The septic response is an extremely complex chain of events involving inflammatory and anti-inflammatory processes, humoral and cellular reactions and circulatory abnormalities (1, 2). The diagnosis of sepsis and evaluation of its severity is complicated by the highly variable and non-specific nature of the signs and symptoms of sepsis (3). However, the early diagnosis and stratification of the severity of sepsis is very important, increasing the possibility of starting timely and specific treatment (4, 5). Biomarkers can have an important place in this process because they can indicate the presence or absence or severity of sepsis (6, 7), and can differentiate bacterial from viral and fungal infection, and systemic sepsis from local infection. With this background in mind, we reviewed the literature on sepsis biomarkers that have been used in clinical or experimental studies to help better evaluate their utility. Introduction The septic response is an extremely complex chain of events involving inflammatory and anti-inflammatory processes, humoral and cellular reactions and circulatory abnormalities (1, 2). The diagnosis of sepsis and evaluation of its severity is complicated by the highly variable and non-specific nature of the signs and symptoms of sepsis (3). However, the early diagnosis and stratification of the severity of sepsis is very important, increasing the possibility of starting timely and specific treatment (4, 5). Biomarkers can have an important place in this process because they can indicate the presence or absence or severity of sepsis (6, 7), and can differentiate bacterial from viral and fungal infection, and systemic sepsis from local infection. Other potential uses of biomarkers include roles in prognostication, guiding antibiotic therapy, evaluating the response to therapy and recovery from sepsis, differentiating Gram-positive from Gram negative microorganisms as the cause of sepsis, predicting sepsis complications and the development of organ dysfunction (heart, kidneys, liver or multiple organ dysfunction). However, the exact role of biomarkers in the management of septic patients remains undefined (8) C-reactive protein (CRP) has been used for many years (9, 10) but its specificity has been challenged (11). Procalcitonin (PCT) has been proposed as a more specific (12) and better prognostic(13) marker than CRP, although its value has also been challenged(14). It remains difficult to differentiate sepsis from other noninfectious causes of systemic inflammatory response syndrome(15), and there is a continuous search for better biomarkers of sepsis. With this background in mind, we reviewed the literature on sepsis biomarkers that have been used in clinical or experimental studies to help better evaluate their utility. The Ideal Diagnostic Marker Of Infection As most infection markers are essential mediators of the inflammatory cascade, their concentrations are likely to be influenced by infective as well as non-infective inflammatory stimuli such as toxic and tissue damaging processes. Establishing a statistically significant correlation between the concentration of a circulating marker and the severity of infection, or showing a significant increase or decrease in the marker’s concentration in an infected infant, is not sufficient to qualify the diagnostic test as being competent or suitable for clinical use. Considering the high mortality and serious morbidity associated with neonatal sepsis, a diagnostic marker with a very high sensitivity (infected infants have a positive test) and negative predictive value (a negative test confidently rules out infection) approaching 100% is desirable because all septic infants with life threatening infection that is totally curable when diagnosed early should be identified and treated.(16, 17) Withholding or delaying antibiotics in false negative cases could have a fatal outcome. Conversely, the lack of reliable clinical signs often results in anticipatory antimi