Increased presepsin levels are associated with the severity of fungal bloodstream infections

Abstract

BackgroundPresepsin is a widely recognized biomarker for sepsis. However, little is known about the usefulness of presepsin in invasive fungal infection. The aim of this study was to determine the plasma levels of presepsin in fungal bloodstream infections and to investigate whether it reflects the disease severity, similar to its utility in bacterial infections.MethodsWe prospectively measured presepsin in plasma samples from participants with fungemia from April 2016 to December 2017. The associations of C-reactive protein, procalcitonin, and presepsin concentrations with the severity of fungemia were statistically analyzed. In vitro assay was performed by incubating Escherichia coli, Candida albicans, and lipopolysaccharide to whole blood cells collected from healthy subjects; after 3 h, the presepsin concentration was measured in the supernatant and was compared among the bacteria, fungi, and LPS groups.ResultsPresepsin was increased in 11 patients with fungal bloodstream infections. Serial measurement of presepsin levels demonstrated a prompt decrease in 7 patients in whom treatment was effective, but no decrease or further increase in the patients with poor improvement. Additionally, presepsin concentrations were significantly correlated with the Sequential Organ Failure Assessment score (r = 0.89, p < 0.001). In vitro assay with co-incubation of C. albicans and human whole blood cells indicated that the viable cells of C. albicans caused an increase in presepsin, as seen with E. coli.ConclusionsPlasma presepsin levels increased in patients with fungal bloodstream infection, with positive association with the disease severity. Presepsin could be a useful biomarker of sepsis secondary to fungal infections.

The Pathogenesis of Sepsis and Potential Therapeutic Targets

“…Interestingly, there are an increasing number of studies illustrating the function of presepsin (sCD14-ST) in the diagnosis of sepsis and prediction of the severity and mortality of the disease [142,143,144]. The serum level of presepsin (sCD14-ST) in the healthy human body is very low when it is not infected, and it is almost undetectable, but the serum level is sharply increased when the microorganisms such as bacteria and fungal are infected [145,146]. Yaegashi et al performed a comparative analysis of plasma presepsin concentrations in 75 healthy volunteers, 80 SIRS patients, and 66 patients with sepsis.…”

Can presepsin be used for screening invasive fungal infections?

“…The preliminary albeit intriguing findings of the two studies investigating the role of presepsin in invasive fungal infections (22,23), along with some notable technical advantages ( Table 1), conceivably pave the way to developing algorithms based on results of both PCT and presepsin testing (measured in combination for screening and differential diagnosis of patients with sepsis), which should then be validated in real life scenarios. Concomitantly increased values of PCT and presepsin would thus appear 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 both bacterial or fungal origin, whilst a disproportionate increase of presepsin values combined with normal or only modestly elevated PCT concentration would be suggestive for invasive fungal infection.…”

“…Although it is hence conceivable that the predictably larger diffusion of presepsin immunoassays would assist filling this gap, two important studies have recently contributed to provide interesting insights on the use of this biomarker for diagnosing invasive fungal infections. Bamba et al studied 11 consecutive patients with fungal sepsis, in whom they measured the concentration of both PCT and presepsin (22). Interestingly, although PCT values were only found to be elevated (i.e., >0.5 ng/mL) in 5/11 patients (diagnostic accuracy, 0.45; 95% CI, 0.17-0.77), two of whom with concomitant bacterial infection, presepsin level was found to be higher than the diagnostic cut-off (i.e., >500 pg/mL) in 10/11 patients (diagnostic accuracy, 0.90; 95% CI, 0.59-1.00).…”

Presepsin as a Diagnostic and Prognostic Biomarker in Sepsis

“…A single prospective study evaluated whether presepsin elevation could be predictive of mortality in disseminated fungal infection with fungemia as it is in bacterial sepsis. The authors noted pronounced presepsin elevation with normal procalcitonin, challenging the notion that presepsin is in fact specific for bacterial infection [ 53 ]. The degree of presepsin elevation appeared to correlate with clinical severity and mortality in patients with disseminated fungemia.…”