Table 3 Sepsis biomarkers that were compared with procalcitonin (PCT) and/or C-reactive protein (CRP) for sepsis diagnosis
Biomarker | Study group | Reference group | Comment [refs] |
|---|---|---|---|
Diagnostic performance similar to or worse than that of PCT and/or CRP | |||
Cell-free DNA (cfDNA) | ICU patients with sepsis | ICU patients with SIRS | |
Copeptin | ED patients with sepsis | ED patients with SIRS | No better than PCT [38] |
ICAM-1 | Patients with necrotic pancreatitis | Patients with sterile necrosis | No better than PCT [39] |
Lipopolysaccharide-binding protein | ED patients with sepsis | ED patients with infection | No better than PCT [40] |
Non-critically ill patients with sepsis | Non-critically ill patients with infection | No better than PCT [41] | |
Children with neutropenia and clinical sepsis and/or bacteremia | Children with febrile neutropenia without infection | No better than PCT [42] | |
Patients with proven bacterial lower respiratory infection | Patients with proven viral lower respiratory infection | No better than CRP [43] | |
Patients treated in internal medicine ward | Healthy control | No better than PCT [27] | |
Pancreatic stone protein | ED patients with sepsis | ED patients without infection | No better than PCT [44] |
sCD22 | Surgical patients with infection after major operation | Surgical patients with SIRS but without infection | Equal value to PCT [45] |
Interleukin (IL)-2 | ICU patients with sepsis | ICU patients with SIRS without infection | No better than CRP [46] |
IL-1β | Neonates with infection and sepsis | Neonates with infection without sepsis | No better than CRP [47] |
RANTES | Neonates with infection | Healthy neonates | No better than CRP [48] |
Neopterin | ICU patients with sepsis | ICU patients without sepsis | |
Macrophage migration inhibitory factor (MIF) | Patients with infection in medical ward or ED | No bacterial infection | No better than PCT [51] |
Adrenomedullin | Neutropenic patients with sepsis | Neutropenic patients with fever and clinically documented infection | No better than PCT [52] |
Pro-adrenomedullin | Sepsis with organ dysfunction and or shock | Patients admitted to coronary unit without infection | No better than PCT [53] |
High-mobility group-box 1 protein (HMGB1) | Infected patients admitted in the ward | Healthy individuals | No better than CRP or PCT [54] |
IL-8 | Neutropenic children with blood culture positive, and/or fever periods with a documented clinical sepsis and/or local infection | Neutropenic children with fever and no infection | No better than CRP [55] |
IL-10 | Patients with bacteremia and SIRS, | Patients with SIRS without bacteremia | Comparable with PCT [56] |
Endocan | Critically ill patients with sepsis and organ dysfunction | Critically ill patients with infection and SIRS | Comparable with PCT [57] |
Pro-atrial natriuretic peptide (ANP) | Burned patients that received antibiotics and had either microbiological confirmation of infection or antibiotics leaded to an improvement in clinical situation | Burned patients without infection | Comparable with PCT [58] |
Pentraxin 3 | Mechanically ventilated patients with ventilator associated pneumonia | Mechanically ventilated patient > 48 h without VAP | No better than CRP [59] |
Hematological patients with bacteremia and/or septic shock | Hematological patients with fever without infection | No better than CRP [60] | |
Better diagnostic value than PCT and/or CRP | |||
Thromboelastometry lysis index | Patients with severe sepsis | Patients after operation without sepsis | Better than PCT [61] |
Decoy receptor 3 | ICU patients with sepsis | ICU patients with SIRS | Positive when PCT was negative [62] |
Group II phospholipase A2 (PLA2-II) | ED patients with sepsis and organ dysfunction | ED patients with SIRS without infection | Better than CRP [63] |
Hepcidin | Infants with sepsis and or bacteremia | Infants with SIRS and not sepsis | Better than CRP [64] |
sCD163 | Patients with sepsis admitted to ICU | Patients with SIRS without sepsis | Better than PCT [65] |
CD64 | ICU patients with sepsis | ICU patients without sepsis | Better than PCT and CRP [66] |
Patients with ventilator associated pneumonia and sepsis | Patients with ventilator associated pneumonia without sepsis | Better than PCT and CRP [67] | |
Serum amyloid A | Full term infants with sepsis | Full term infants with risk for sepsis but without sepsis | Earlier increase in neonates with early onset sepsis than CRP [68] |
Heparin-binding protein | Patients with sepsis for less than 48 h | Patients with infection without sepsis | Better than CRP and PCT [69] |
Delta-like canonical Notch ligand 1 (DLL1) | Patients with abdominal infection or surgical site associated infection | Surgical patients, trauma patients without infection, and healthy volunteers | Better than CRP and PCT [70] |
Conflicting findings | |||
IL-6 | Critically ill patients with sepsis | Patients with SIRS without infection | IL-6 was not found to have lower diagnostic utility compared to PCT (meta-analysis) [71] |
Cirrhotic patients with infection at admission to ICU | Cirrhotic patients without sepsis | IL-6 was found to increase earlier than PCT in cirrhotic patients [72] | |
sCD25 | ED patients with infection | ED patients with suspected infection but finally infection excluded | Equal diagnostic value to PCT for diagnosis of infection in ED [44] |
Patients admitted in ICU with infection and SIRS | Patients with SIRS without sepsis | Better performance than PCT to identify Sepsis I at ICU admission [73] | |
Calprotectin | ICU patients with infection | ICU patients without sepsis | Better than CRP and PCT [74] |
Patients after major operation who developed sepsis | Patients after major operation who did not develop sepsis | Similar value to PCT [75] | |
IL-27 | Critically ill children with sepsis | Children with SIRS without infection | Better than PCT [76] |
ICU patients with sepsis | ICU patients without sepsis | No better than PCT [77] | |
sTREM | ICU patients with sepsis | ICU patients with SIRS | Better than PCT [78] |
ICU patients with sepsis | ICU patients with SIRS | No better than PCT and CRP [79] | |
Presepsin (CD14) | ED patients with sepsis | ED patients with at least two criteria of SIRS without sepsis | Better than PCT in diagnosis of sepsis in ED [80] |
Critically ill patients with sepsis and organ dysfunction | Critically ill patients without infection | No better than PCT regardless of the presence or not of AKI [17] | |
Neonates with SIRS and positive blood cultures | Neonates with SIRS with negative blood cultures | Better than PCT [81] | |
Better performance when combined with PCT and/or CRP | |||
IL-6 | Neonates with infection within the first week of life | Neonates with suspicion of infection but finally excluded within the first week of sepsis | Combination with CRP in neonates with suspected sepsis [82] |
CD64 | Neonates with sepsis | Healthy controls | Combination with PCT and CRP for diagnosis of neonatal sepsis [83] |
Leptin | Patients with community acquired pneumonia with sepsis or complicated intraabdominal infection | SIRS without infection, healthy controls | Combination with CRP [84] |
Pro-adrenomedullin | Septic patients | Patients with SIRS without sepsis | |
suPAR | Septic patients admitted to ICU | Critically ill patients with SIRS without infection and healthy controls | Combination with PCT for diagnosis of sepsis on day 1 of sepsis [86] |
CD11b | Patients with Gram (+) infection | Patients with Gram (−) infection | Combination with CRP for differentiation from Gram (−) infection [87] |
Fibrinogen | Neutropenic patients with sepsis | Neutropenic patients with fever without infection | Combination with CRP for diagnosis of sepsis [88] |
BNP and antithrombin | Neutropenic patients with fever and bacteremia | Neutropenic patients with fever without infection | Combination with PCT for diagnosis of Gram (−) bacteremia [88] |
IL-27 | Pediatric patients with sepsis | Pediatric patients with SIRS without infection | Improvement of diagnostic accuracy of PCT for diagnosis of sepsis [77, 89] |
α-2 macroglobulin | Surgical patients with sepsis | Surgical patients with SIRS without sepsis | Combination with PCT to exclude sepsis in surgical patients [90] |
Decoy receptor 3 and uPAR | Patients with sepsis | Patients with SIRS without infection, healthy volunteers | Combination with PCT for diagnosis of sepsis [91] |