Current evidence and limitation of biomarkers for detecting sepsis and systemic infection

Sepsis was recently redefined as a life-threatening disease involving organ dysfunction caused by a dysregulated host response to infection. Biomarkers play an important role in early detection, diagnosis, and prognostication. We reviewed six promising biomarkers for detecting sepsis and systemic infection, including C-reactive protein (CRP), procalcitonin (PCT), interleukin-6 (IL-6), CD64, presepsin, and sTREM-1. Among the recent studies, we found the following risks of bias: only a few studies adopted the random or consecutive sampling strategy; extensive case-control analysis, which worsened the over-estimated performance; most of the studies used post hoc cutoff values; and heterogeneity with respect to the inclusion criteria, small sample sizes, and different quantitative synthesis methods applied in meta-analyses. We recommend that CD64 and presepsin should be considered as the most promising biomarkers for diagnosing sepsis. Future studies should enroll a larger sample size with a cohort rather than a case-control study design. A random or consecutive study design with a pre-specified laboratory threshold, consistent sampling timing, and an updated definition of sepsis will also increase the reliability of the studies. Further investigations of appropriate specimens, testing assays, and cutoff levels for specific biomarkers are also warranted.