Can presepsin be used for screening invasive fungal infections?

Invasive fungal infections are a major healthcare issue, accounting for approximately 20% of all sepsis cases. Like all other forms of sepsis, early and accurate diagnosis is pivotal for establishing timely and appropriate management, thus reversing an otherwise unfavourable outcome which is frequently characterized by multiple organ dysfunction and death. Although the gold standard for diagnosing invasive fungal infection is still represented by conventional mycological testing, including microscopic examination and/or blood culture, these methods have some well-known drawbacks. Additional investigations, such as serologic testing, measurement of 1,3-beta-D-glucan, mannan antigen or anti-mannan antibodies and molecular biology are also plagued by some technical and practical limitations, which would make the development of alternative approaches highly advisable. The clinical significance of measuring procalcitonin for diagnosing and managing bacterial sepsis is now unquestionable, whilst inconsistent evidence has been provided on its diagnostic value for invasive fungal infections. Presepsin, also known as soluble CD14 subtype, is a glycoprotein fragment mostly produced by macrophages or monocytes in response to infections. The potential usefulness of this innovative biomarker has only recently emerged in sepsis diagnostics. Some preliminary evidence suggests that its concentration is not only markedly elevated in patients with invasive fungal infections, but is more predictive of outcomes than other conventional biomarkers. These preliminary findings lead the way to developing diagnostic algorithms based on results of both procalcitonin and presepsin, which should then be validated in real life scenarios. Theoretically, concomitantly increased values of these biomarkers would be suggestive of bacterial sepsis (especially Gram-negative bacterial sepsis) or mixed infection, non-diagnostic values of both biomarkers may enable to safely rule out sepsis of bacterial or fungal origin, whilst a disproportionate increase of presepsin values combined with normal or only modestly elevated procalcitonin concentration may be suggestive of invasive fungal infections.