Table 1.
Cohorts studies of biomarkers and biomarker panelsa
| Setting and study design (reference) | Biomarker | Specificity (%) | Sensitivity (%) | Cutoffd | AUC | Direction of effect | Clinical relevance | Verification of infection (diagnostic reference standard) |
|---|---|---|---|---|---|---|---|---|
| Correlation of PCT, CRP, and IL-6 levels with infection likelihood or septicemia in emergency department patients with suspected sepsis (276) | PCT | 63–97 (infection likelihood), 38–90 (septicemia) | 68–18 (infection likelihood), 91–47 (septicemia) | 0.1–3.0 ng/ml | 0.72 (infection likelihood), 0.79 (septicemia) | ↑ | PCT, IL-6, and CRP highly correlate with several infection parameters but are inadequately discriminating to be used independently as diagnostic tools | Determined retrospectively from patient files by specialists blinded to biomarker data |
| IL-6 | 67–96 (infection likelihood), 34–89 (septicemia) | 58–14 (infection likelihood), 90–27 (septicemia) | 40–500 pg/ml | 0.69 (infection likelihood), 0.70 (septicemia) | ↑ | |||
| CRP | 33–88 (infection likelihood), 39–88 (septicemia) | 90–43 (infection likelihood), 82–31 (septicemia) | 40–100 mg/dl | 0.75 (infection likelihood), 0.67 (septicemia) | ↑ | |||
| Correlation of PCT, IL-6, and IL-8 with sepsis in 78 critically ill patients with SIRS and suspected infection (102) | PCT | 78 | 97 | 1.1 ng/ml | 0.92 | ↑ | Addition of PCT to the standard workup of critically ill patients with suspected sepsis could increase diagnostic certainty | Determined retrospectively from patient files by specialists blinded to biomarker data |
| IL-6 | 72 | 67 | 200 pg/ml | 0.75 | ↑ | |||
| IL-8 | 78 | 63 | 30 pg/ml | 0.71 | ↑ | |||
| Cohort study of 32 ICU patients undergoing cardiac surgery with cardiopulmonary bypass, 11 of these patients with SIRS and 6 of these with sepsis (69) | BPW | 93 | 100 | 0.465%T/s | 0.95 | BPW has potential clinical applications in sepsis diagnosis in the postoperative period following cardiac surgery under CPB | Sepsis was defined as SIRS associated with a documented infection, determined by 2 experts taking into account complete medical data | |
| PCT | 0.70 | ↑ | ||||||
| CRP | 0.66 | ↑ | ||||||
| Cohort study of 200 ICU patients to detect sepsis at admission and sepsis during ICU stay (308) | BPW | 92 (sepsis at admission), 76 (sepsis during ICU stay) | 79 (sepsis at admission), 81 (sepsis during ICU stay) | 0.075%T/s | 0.83 | ↑ | BPW may be useful as a simple diagnostic marker of sepsis; specificity can be increased by combing BPW with PCT; these tests may be more useful to rule out sepsis | Diagnosis of sepsis made by treating clinician (SIRS and documented or suspected infection), blinded to biomarker data |
| PCT | 79 (sepsis at admission), 75 (sepsis during ICU stay) | 83 (sepsis at admission), 83 (sepsis during ICU stay) | 1 ng/ml | ↑ | ||||
| BPW plus PCT | 95 (sepsis at admission), 94 (sepsis during ICU stay) | 79 (sepsis at admission), 81 (sepsis during ICU stay) | ↑ | |||||
| Cohort study of 161 patients with at least 2 SIRS criteria presenting to the medical emergency department and department of infectious diseases suspected of community-acquired infection (129) | suPAR | 0.67 | 0.35 | 2.7 μg/liter | 0.50 | ↑ | Measurements of suPAR, sTREM-1, and MIF had limited value as single markers, whereas PCT and CRP exhibited acceptable diagnostic characteristics; combined information from several markers improves diagnostic accuracy | Diagnosis of infection determined retrospectively by 2 infectious disease specialists based on clinical and laboratory findings, response to treatments, radiographic and other imaging procedures, and both positive and negative bacteriological, viral, and parasitic findings during the first 7 days of admission |
| sTREM-1 | 0.40 | 0.82 | 3.5 μg/liter | 0.61 | ↑ | |||
| MIF | 0.47 | 0.80 | 0.81 μg/liter | 0.63 | ↑ | |||
| PCT | 0.58 | 0.80 | 0.28 μg/liter | 0.72 | ↑ | |||
| Neutrophil count | 0.74 | 0.64 | 8.5 × 109 cells/liter | 0.74 | ↑ | |||
| CRP | 0.60 | 0.86 | 59 mg/liter | 0.81 | ↑ | |||
| Composite 6-marker test | 0.78 | 0.88 | 0.88 | ↑ | ||||
| Prospective study including inceptive and validation cohorts of unselected ICU patients to test performance of a combination biomarker (“bioscore”)b with sTREM-1, PCT, and PMN CD64 index to diagnose sepsis (91) | sTREM-1 | 86.3 | 53.2 | 755 pg/ml | 0.73 | ↑ | A bioscore of 0 excluded the presence of sepsis (101 of 105 [96.2%] patients); 129 of the 134 patients (96.3%) with a bioscore of 2 or 3 (44.6% of the cohort) were septic; bioscore of 1 was not helpful (61 patients [20.3%]) | Diagnosis of sepsis made retrospectively by 2 intensivists blinded to biomarker data |
| PCT | 84.9 | 83.1 | 1.55 ng/ml | 0.91 | ↑ | |||
| CD64 index | 95.2 | 84.4 | 1.62 | 0.95 | ↑ | |||
| Bioscore (derived from the 3 markers) | 0 = sepsis unlikely; 2 or 3 = sepsis likely | 0.95 | ↑ | |||||
| Cohort study of 293 medical ICU patients (98) | CD64 index | 89 | 63 | 2.2 | 0.8 | ↑ | As a result of its weak sensitivity, the CD64 index may not be practically recommended but may be useful in combination with a more sensitive biological marker | Bacterial infection |
| Cohort study of 109 critically ill neonates (118) | CD64 index | 88.7 | 94.6 | 1.19 | 0.94 | ↑ | The CD64 index is a useful and inexpensive test for improving the diagnosis and management of hospital patients with bacterial infection | Clinical diagnosis of sepsis and/or positive blood cultures |
| Prospective cohort study with 60 infants with 104 episodes to detect probable clinical sepsis, septicemia, or NEC (191) | ApoSAA scorec | 76 | 96 | 0.199 | 0.93 | ↑ | The ApoSAA score could potentially allow early and accurate diagnosis of sepsis/NEC and helps to guide antibiotic therapy | Clinical diagnosis of sepsis and/or positive blood cultures |
a
AUC, area under the concentration-time curve; PCT, procalcitonin; CRP, C-reactive protein; IL-6, interleukin-6; BPW, biphasic waveform derived from activated partial thromboplastin time; suPAR, soluble urokinase-type plasminogen activator receptor; sTREM-1, soluble triggering receptor expressed on myeloid cells 1; MIF, macrophage migration inhibitory factor; CD64 index, immunoglobulin Fc fragment receptor I (FcγRI) CD64 on neutrophils.
b
The bioscore ranged between 0 (all three markers below their respective thresholds) and 3 (all three markers above their thresholds).
c
The “ApoSAA score” is a biomarker panel identified through a proteomic approach. The ApoSAA score is computed from plasma concentrations of proapolipoprotein CII (Apo) and a desarginine variant of serum amyloid A (SAA).
d
%T/s, transmittance percentage per second.