Repetitive Assessment of Biomarker Combinations as a New Paradigm to Detect Sepsis Early

For the diagnostic workup of sepsis, the 2021 Surviving Sepsis Campaign guidelines recommend to clinically search for infection while monitoring the dysregulated host response with the goal to start antibiotics and organ failure support in less than 1 h. Unfortunately, while highly sensitive, this approach lacks specificity, which might eventually result in antibiotic overuse and further contribute to the burden of antimicrobial resistance. Biomarkers, such as leukocytes, C-reactive protein (CRP), and procalcitonin (PCT), although widely used at the bedside, improve neither the sensitivity nor the specificity of this approach. Accordingly, current guidelines recommend against their use, except for antibiotic de-escalation. In such a context, a diagnostic approach that includes biomarkers with good negative predictive values—i.e., able to exclude rather than to confirm sepsis - could reduce the number of patients unnecessarily treated with antibiotics. In this chapter, we review the performance of pancreatic stone protein (PSP), a novel sepsis biomarker available for point-of-care use. In a recent meta-analysis, PSP performed better than CRP and PCT for the diagnosis of infection and its combination with CRP further improved its accuracy. Interestingly, a recent prospective multicenter study confirmed PSP’s capacity to detect nosocomial sepsis several days before clinical signs occurred. Capitalizing on the good negative predictive value of PSP and its ability to detect signals of sepsis even in the pre-symptomatic phase, we propose to integrate combined CRP and PSP measurements in patients suspected of having sepsis and to repeat them daily in those remaining at risk of developing it.