41 Biomarkers in sepsis 0 100 200 300 400 500 600 700 800 1980 1985 1990 1995 2000 2005 2010 2015 Numbers of publications Figure 2: Articles published on biomarkers in sepsis. An exploratory search in the PubMed database regarding “sepsis AND biomarkers” shows an increase in number of publications from 1980 to 2015. Traditional (protein) biomarkers Many protein biomarkers have been evaluated for their ability to discriminate between sepsis and non-infectious conditions. In critical care antibiotic therapy is almost invariably initiated upon (even modest) suspicion of infection. However, the infection diagnosis in critically ill patients is likely overestimated. A recent study involving > 2500 patients treated for sepsis on the Intensive Care Unit (ICU) reported that 13% had a post-hoc infection likelihood of “none”, and an additional 30% of only “possible”, as determined by well-defined criteria and making use of all clinical, radiological and microbiological information [16]. Remarkably, patients who were initially treated for sepsis but were post-hoc determined to have noninfectious disease had a higher mortality rate [16], thereby underlining the necessity for a diagnostic biomarker to correctly diagnose sepsis. By far the most studied biomarker and the only biomarker that is currently implemented in clinical sepsis guidelines is PCT. PCT levels rise in response to a proinflammatory stimulus. Because of the short time between stimulus and induction of PCT (detectable after 4 hours, peak at 6 hours)[17, 18] and its long half-life of 25 to 30 hours [19], it is a widely investigated biomarker in sepsis. A recent meta-analysis showed a pooled sensitivity of 0.77 (95% confidence intervals (CI) 0.72-0.81) and a pooled specificity of 0.79 (95% CI 0.74-0.84) of PCT to distinguish between sepsis and a systemic inflammatory response syndrome of non-infectious origin [20]. Levels of PCT between 0.1 and 0.5 ng/ml suggest presence of bacterial infection for which antimicrobial therapy is required [21], but no consensus has been reached about the correct cut-off value for 3
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