Neutrophil CD11b more information could distinguish septic pediatric patients from those with possible infection with good sensitivity and specificity [33]. The sensitivity and specificity of the other 11 biomarkers used to diagnose early sepsis were not reported or were less than 90%.Biomarkers can be more useful to rule out sepsis than to rule it in. We identified three biomarkers with high negative predictive value to rule out sepsis: PCT (99% at a cut-off value of 0.2 ng/ml) [34]; activated partial thromboplastin time (aPTT) waveform (96%) [35]; and fibrin degradation products (100% for Gram-negative sepsis by ELISA assay) [36]. It is important to emphasize that culture-positive sepsis was generally used as the gold standard in all these studies, although cultures may remain negative in many patients with sepsis.

The majority of the biomarkers that we identified in our search were assessed for their ability to differentiate patients likely to survive from those likely to die. Indeed, any biomarker is expected to have some prognostic value and sepsis biomarkers are no exception; however, this is not an absolute rule because some sepsis biomarkers failed to have prognostic value [37-39]. Moreover, sensitivity and specificity were tested in only some of the proposed prognostic markers, and none had sufficient (more than 90%) sensitivity and specificity to predict which patients were at greater risk of dying due to sepsis. Other biomarkers were assessed for their ability to predict the development of multiple organ failure and to evaluate response to therapy.

It is known that the extent of infection and the severity of organ failure has a significant impact on the prognosis of patients with sepsis. Additionally, the response to therapy varies among patients. Recently, the PIRO model has been proposed as a way of stratifying septic patients according to their Predisposing condition, the severity of Infection, the Response to therapy and the degree of Organ dysfunction [20]. In the future, sepsis biomarkers may contribute to this model of classification rather than just being used as prognostic markers.No biomarker has, therefore, established itself sufficiently to be of great help to clinicians in everyday clinical practice. As each biomarker has limited sensitivity and specificity, it may be interesting to combine several biomarkers [40,41]; however, this hypothesis requires further study.

A clinical study showed that the combination of aPTT waveform with PCT increased the specificity AV-951 of the aPTT waveform in the diagnosis of sepsis [35]. Studies using panels of sepsis biomarkers have also provided encouraging results [42-44]. The cost-effectiveness of all these methods must also be evaluated.In this study, we tried to categorize the sepsis biomarkers according to their pathophysiological role in sepsis.