Novel biomarkers for distinguishing bacterial from non-bacterial infection: a systematic review
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Background
Accurately distinguishing bacterial from non-bacterial infections is essential to guide antibiotic use but remains clinically challenging. Current biomarkers such as C-reactive protein and procalcitonin have limited diagnostic accuracy.
Objective
To identify novel blood protein biomarkers with clinically acceptable performance for differentiating bacterial from non-bacterial infections.
Methods
Following PRISMA guidelines, we systematically searched Medline and prior reviews (2010–2024) for studies evaluating the diagnostic accuracy of protein biomarkers in serum or plasma for bacterial infection. Biomarkers were considered clinically useful if sensitivity ≥90%, specificity ≥80%, or AUC ≥0.9, was reported in studies with low risk of bias (assessed via modified QUADAS-2).
Results
From 2,236 records, 47 studies were included, assessing 50 individual biomarkers and 12 signatures. Two individual biomarkers (LCN2, IFN-α) and three multi-marker signatures (TRAIL+IP-10+CRP, E-selectin+IL-18+NCAM1+LCN2+IFN-γ, and E-selectin+IL-18+NCAM1+LG3BP+LCN2+IFN-γ) met pre-defined performance thresholds. TRAIL+IP-10+CRP showed consistent performance across six studies.
Conclusions
TRAIL+IP-10+CRP and LCN2 are promising host-response biomarkers for bacterial infection. Multi-marker panels may enhance diagnostic accuracy but require further validation. These tools have the potential to improve clinical decision-making and reduce unnecessary antibiotic use.
