**7. Conclusions**

Within the last decade, a broad range of molecular biomarkers for sepsis has been reported. One of the most promising emerging biomarkers is presepsin, gaining relevance year by year. After the initial report in 2005, a strong body of literature comprised of more than 280 clinical studies, systematic reviews, and meta-analyses, indicated that presepsin could be used as a relevant routine daily clinical tool for early diagnosis, risk stratification, and predicting clinical progression, short-term and long-term outcomes, and guiding therapeutic management in adult, neonates, and pediatric sepsis patient. That presepsin is still a marker in focus, is shown by the fact that almost 70% of studies were published in the last 5 years. With the change of sepsis definition in Sepsis-3, the utility of presepsin is currently being reevaluated, with consistently encouraging results. In addition, presepsin concentration can now be routinely measured in whole blood, in approximately 15 min, using point-of-care devices in different clinical settings (ED, ICU). A potential advantage of presepsin resides in the possibility of its measuring in non-invasive biological fluids such as urine, saliva, as well as tracheal aspirate for adults, children, and infants.

Despite presepsin represents a promising biomarker, it still faces numerous challenges and criticisms that require further elucidation. The studies in favor of the use of presepsin are heterogenous in the sense they use the sepsis-2 definition, and examine clinically heterogenic patient groups at risk of sepsis in a variety of different settings, with the small sample size as a common limitation.

Inter-assay disagreement can represent a confounding factor in the interpretation of test results in different studies. The definition of an optimal cut-off is very important. Instead of using static threshold presepsin concentrations, serial monitoring of presepsin levels would prove more helpful to clinicians to follow an individual patient's response to therapy. Further prospective studies with larger and more diverse populations are required to establish the presepsin cut-off for the diagnosis and prognosis of infections. Consensus regarding time sampling strategy in infants is particularly of great importance. Also, conversion of presepsin level from pg/ml to multiple medians as measurement units will be more than justified in the assessment of perinatal sepsis. Studies that evaluated the impact of presepsin on therapeutic decisions are still limited. Specifically designed randomized clinical trials are needed to determine the usefulness and safety of early measurement of presepsin to guide early empirical antibiotic treatment, particularly in preterm newborns. Will presepsin be incorporated in antimicrobial stewardship programs that will contribute to reducing antimicrobial overuse in septic patients without compromising the clinical outcome, remains to be seen. Although, current evidence on biomarkers and pharmacokinetic optimization of antibiotics in critically ill patients is limited, maybe in the future, presepsin-based drug monitoring for dose optimization will be proposed.

As it has already been touched on in the chapter, in some clinical conditions (renal failure, burns, etc.), presepsin levels can be altered in the absence of sepsis. Presepsin levels may be higher in some physiological conditions like in preterm newborns and advanced age patients, in which concentrations reach the threshold at which the diagnosis of sepsis would be highly suspected in human beings. Presepsin is also affected by the translocation of intestinal microbial flora. Future studies are necessary, for the identification of these conditions and the determination of appropriate cut-off values based on age and associated diseases.

*Presepsin as a Diagnostic and Prognostic Biomarker in Sepsis DOI: http://dx.doi.org/10.5772/intechopen.107955*

Many studies in different clinical settings that compared the diagnostic and prognostic efficacy of presepsin with CRP and/or PCT, reported controversial results. Presepsin does not appear to be clearly superior to the biomarkers commonly used in the assessment of sepsis, although mainly performances place presepsin at the level of PCT. Compared to PCT, the significance of presepsin elevation is easy to understand, as it results from a dose–response mechanism of the host-pathogen interaction. Presepsin increases with every type of bacteria and fungi. In neonatal sepsis, presepsin compared to PCT is more effective in diagnosing and guiding therapy.

The combination of presepsin with traditional sepsis biomarkers CRP and/or PCT, or with other novel biomarkers (triggering receptor expressed on myeloid cells-1, neutrophil cluster of differentiation-64, soluble urokinase-type plasminogen activator receptor, mid-regional pro-adrenomedullin, cell-free DNA, microRNAs, interleukin-27, etc) into a bio-score, together with physician expertise and clinical judgment, may be particularly useful in the diagnosis of sepsis or the risk stratification of patients with sepsis. High-quality prospective studies with larger, diverse populations with an eye on specific subgroups are more than warranted. It seems that presepsin merits further study to delineate its specific area of utility.
