New Approaches to Sepsis: Molecular Diagnostics and Biomarkers

Abstract

SUMMARY Sepsis is among the most common causes of death in hospitals. It arises from the host response to infection. Currently, diagnosis relies on nonspecific physiological criteria and culture-based pathogen detection. This results in diagnostic uncertainty, therapeutic delays, the mis- and overuse of antibiotics, and the failure to identify patients who might benefit from immunomodulatory therapies. There is a need for new sepsis biomarkers that can aid in therapeutic decision making and add information about screening, diagnosis, risk stratification, and monitoring of the response to therapy. The host response involves hundreds of mediators and single molecules, many of which have been proposed as biomarkers. It is, however, unlikely that one single biomarker is able to satisfy all the needs and expectations for sepsis research and management. Among biomarkers that are measurable by assays approved for clinical use, procalcitonin (PCT) has shown some usefulness as an infection marker and for antibiotic stewardship. Other possible new approaches consist of molecular strategies to improve pathogen detection and molecular diagnostics and prognostics based on transcriptomic, proteomic, or metabolic profiling. Novel approaches to sepsis promise to transform sepsis from a physiologic syndrome into a group of distinct biochemical disorders and help in the development of better diagnostic tools and effective adjunctive sepsis therapies.

The role of CRP, PCT, IL-6 and presepsin in early diagnosis of bacterial infectious complications in paediatric haemato-oncological patients

“…Moreover, we found out poor sensitivity for ability to identify bacteraemia, moderate sensitivity and low PPV for discrimination of sepsis symptomatology. CRP level is also elevated during non-infectious inflammatory states including patients with malignancy, during oncology treatment or after surgery [3,11]. This is another documented limitation.…”

“…Cytokines are detected in serum in the early stages of infection, and particularly in bacterial infections, they may be higher than CRP in early disease [4,11,12,35]. IL-6, IL-8, and IL-10 have been shown to have good negative predictive value for bacteraemia in adult and paediatric oncology patients [4,6,13].…”

Procalcitonin as diagnostic biomarker of sepsis

“…2,10,11 Although by defi nition these might indicate the pattern of diagnosed infections, the focus on the Middle East would have led to individuals with this viral infection in other geographical regions being missed. Latest WHO guidelines now recommend universal screening to defi ne the epidemiology of this novel coronavirus.…”

“…2,[7][8][9][10][11][12][13] Another lesson was that although laboratory testing is important to confi rm infection, it does not replace accurate case defi nitions, regular updates as information…”

“…1 At present, procalcitonin is a biomarker for infection most used in hospitals and seems to have a higher diagnostic accuracy than other traditional biomarkers of infl ammation. 2 Particularly, procalcitonin has attracted a great deal of attention as a potential means to guide antibiotic stewardship, reducing inappropriate antimicrobial use and associated resistance. 3 Several meta-analyses have assessed procalcitonin as a marker of sepsis.…”