Sepsis remains a major healthcare problem despite significant investment to raise awareness about this life-threatening condition in the past two decades. The 2016 sepsis guidelines emphasized the need for early recognition and prompt treatment initiation; however, both laboratorians and physicians recognize that even today’s best biomarkers for sepsis management are not good enough for detecting sepsis in a timely manner.

The limitations of current diagnositic markers and the promise of emerging biomarkers were highlighted yesterday morning in The  Journal of Applied Laboratory Medicine Hot Topics of 2019 session. “Early detection and risk assessment of sepsis is key, just as it is in other conditions including stroke, myocardial infarction, and cancer,” emphasized Robert Christenson, PhD, The Journal of Applied Laboratory Medicine’s editor-in-chief.

Richard Sweet, MD, kicked off the session by shedding new light on the pathogenesis of sepsis. Laboratorians know sespsis as an overwheling immune response to infection that triggers widespread inflammation leading to organ damage. But much about the pathophysiology of sepsis is complicated and less well understood, hindering the development of effective diagnostics and therapeutics.

In his presentation, Sweet discussed the role of inducible nitric oxide synthase (iNOS) in initiation of secondary necrosis and sepsis, which has major implications for both sepsis diagnosis and treatment. In particular, microvesicle-associated iNOS (MV-A iNOS) kills cells and produces microperorations leading to multiple organ failure. Sweet presented data from more than 200 ICU patients where iNOS was detected only in patients with sepsis or those who developed sepsis, with earlier detection than blood culture assays.

“Like other major mortality causes, there is heterogeneity in that sepsis can be from a bacterial or viral etiology,” Christenson explained. In his talk, Christenson presented evidence for the role of human neturophil lipocalin (HNL) in distingushing bacterial and viral infections in hospitalized patients. HNL is a glycoprotein released from activated neutrophils during bacterial infections. It can distinguish between bacterial and viral infections with greater than 90% accuracy. “Compared to other biomakers, the performance of HNL holds substantial promise,” said Christenson. Researchers hope to develop a point-of-care solution that can identify acute bacterial infections in less than 10 minutes, which would be a major advance in sepsis management, he noted.   

Jessica Colon-Franco, PhD, summed up the session providing an overview of how the sepsis definitions and the scoring systems have evolved to recongnize sepsis early for prompt treatment and management. She explained the limitations and strengths of current sepsis biomarkers in clinical use, including procaclitonin. She presented evidence supporting the use of procalcitonin in certain disease contexts, while recognizing the unmet need for an ideal sepsis marker. Colon-Franco noted that while several European studies have reported reduction in antibiotic usage with procalcitonin-guided decision making, the largest U.S. multi-center study to date did not report a similar benefit.

Though the emerging biomarkers presented in the session hold great promise, extensive development and validation of these technologies will likely take time before they are incorporated into routine clinical practice. Many experts recognize that multiple biomarkers will likely be necessary for diagnosis and management of sepsis. “Utilization of novel biomarkers [and] strategies, along with multi-disciplinary collaboration between microbiology, clinical chemistry, infectious disease, and intensivists” will be the future of sepsis care and diagnosis, Christenson said.