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Diagnosis of bacterial sepsis: why are tests for bacteremia not sufficient?

Sepsis is a leading cause of morbidity and mortality and health system cost and is a major pain point for health systems in the United States whose payments are now partially tied to sepsis performance criteria. Although frequently used synonymously with bacteremia, sepsis was most recently redefined (‘Sepsis3ʹ) as a life-threatening dysregulated host immune response to infection [1]. Sepsis as a syndrome can be caused by bacterial, viral, fungal, or parasitic infections, and can be mimicked by non-infectious etiologies, making diagnosis particularly challenging where an infectious source is not immediately apparent. Furthermore, early treatment with appropriate antimicrobials has been shown to reduce morbidity and mortality in cases of bacterial infection. On the other hand, antibiotics can have substantial side effects (1 in 5 hospital patients treated with parenteral antibiotics has an adverse drug event, including C. difficile infection) [2] and indiscriminate and prolonged use causes antimicrobial resistance [3]. Thus, rapid diagnosis of sepsis, and its underlying cause, is of great interest: as Kibe wrote, ‘the search for a highly accurate biomarker of sepsis has become one of the holy grails of medicine’ [4].