Considering the microbial etiology, PCT resulted increase in gram-negative sepsis and septic shock diagnosis but lower in the case of gram-positive and fungal etiologies. This difference could be referred to the different Toll-like receptor signaling pathways activation producing different pro-inflammatory cytokines: gram-negative bacteria lipopolysaccharides (LPS) is recognized by toll-like receptor 4 (TLR4), while Grampositive lipoteichoic acid (LTA) by toll-like receptor 2 (TLR2).Fungal pathogens are recognized by C-type lectin receptors (CLRs) inducing cytokines' release as IL-1β, IL-10, and IL-6, resulting in moderately elevated PCT levels that are influenced by Interferon (IFN)-γ inhibition and its relative levels.In gram-positive bloodstream infection, the highest PCT values were detected in the case of S. aureus and Enterococcus spp.These factors probably contributed to the observed differences in PCT values reported in gram-negative, gram-positive and fungal sepsis.Conversely, MR-proADM values are homogeneously distributed within the different microbial classes, but median values tend to increase significantly when sepsis is complicated towards septic shock. These data, published by the Spoto et al.'s study [67] , confirm this marker's prognostic role in septic patients regardless of microbiological etiology.In case of gram-negative, PCT values were significantly different between sepsis and septic shock only in case of E. coli and S. maltophilia, whereas MR-proADM was significantly higher in septic shock also in K. pneumoniae and P. aeruginosa. This could suggest that while PCT is an excellent diagnostic marker, it is not useful enough for prognostic purposes being influenced by the microbial etiology.In fact, sepsis by Enterobacteriaceae is characterized by the highest PCT values, especially in the case of Proteus mirabilis.Contrariwise, MR-proADM was not different between Enterobacteriaceae and other gramnegative pathogens, but its values were significantly higher in the case of Citrobacter spp. and Klebsiella spp. suggesting that these pathogens could induce more severe sepsis, as well as Candida albicans and Candida tropicalis. MR-proADM showed homogenous values distribution between different gram-positive isolates, but with significantly higher values in septic shock from S. aureus, Enterococcus spp. and Streptococcus spp.These results confirm the prognostic role of MR-proADM in disease progression towards septic shock and organ failure; especially in gram-positive and fungal infection where PCT is not specific enough.In case of polymicrobial etiology, PCT median values were significantly higher when gram-negative isolates were present. This is in agreement with the suggestion that gramnegative isolates generally stimulate PCT release more than other microorganisms.Conversely, even if MR-proADM values were higher in the presence of gram-negative isolates, no significant difference was found between the various polymicrobial associations having values homogeneously distributed.In conclusion, in gram-negative sepsis, PCT and MR-proADM could give complementary information to be used at diagnostic and prognostic purposes.PCT's etiological diagnostic role represents an advantage to provide early tailored antimicrobial therapy since the first hours of the septic event. PCT accuracy was lower in gram-positive and fungal sepsis discrimination, because of the lower PCT ability to identify these etiologies, as previously reported.MR-proADM discriminating cut-offs were homogeneously distributed in Gram-negative and Gram-positive sepsis and higher in septic shock. These data agree with the prognostic role of this biomarker; in fact, values are not influenced by the different pathogen etiologies but are increased in case of disease severity progression and in case of fungal sepsis that generally underlines severe clinical conditions. MR-proADM combination with PCT could aid in predicting sepsis patient's progression towards septic shock and multiorgan failure.The combination of both markers could help predict the etiology and the severity of sepsis:PCT and MR-proADM combination represents an advantage for sepsis diagnosis and prognosis to provide early tailored therapy and risk stratification for 90-days mortality. [17] support the prognostic role of MR-proADM and PCT, particularly in respiratory tract infections, urinary tract infection, and sepsis. Also of interest is the possibility that the combined use of the two biomarkers can predict a subsequent hospitalization of febrile patients accessing the ED.