N Menestrina

Procalcitonin levels in surgical patients at risk of candidemia

OBJECTIVE Although the majority of cases of sepsis in intensive care unit (ICU) patients are due to bacterial infection, fungal infections are common and their early identification is important so that appropriate treatment can be started. Biomarkers have been used to aid diagnosis of bacterial infections, but their role in fungal infections is less defined. In this study we assessed the value of procalcitonin (PCT) levels for the diagnosis of candidemia or bacteremia in septic patients. METHODS We prospectively recorded PCT levels in 48 critically ill surgical patients with signs of sepsis and at high risk for fungal infection, and compared levels in patients with candidemia and bacteremia. RESULTS Bacterial species were isolated from blood cultures in 16 patients, Candida species in 17, and mixed bacterial and Candida species in 2 patients. PCT levels were less elevated in patients with candidemia (median 0.71 [IQR 0.5-1.1]) than in those with bacteremia (12.9 [2.6-81.2]). A PCT value less than 2 ng/ml enabled bacteremia to be ruled out with a negative predictive value of 94%, and had a similar positive predictive value for candidemia. CONCLUSIONS Our data indicate that a low PCT value in a critically ill septic patient is more likely to be related to candidemia than to bacteremia.

Circulating neutrophils of septic patients constitutively express IL-10R1 and are promptly responsive to IL-10

Previous studies have demonstrated that neutrophils isolated from the blood of healthy donors do not respond to IL-10 in terms of either activation of signal transducer and activator of transcription-3 (STAT3) tyrosine phosphorylation or induction of suppressor of cytokine signalling (SOCS)-3 protein, unlike autologous mononuclear cells. This was explained by the fact that circulating neutrophils of healthy donors express only IL-10R2, but not IL-10R1, the latter IL-10R chain being essential for mediating IL-10 responsiveness. In this study, we report that peripheral blood neutrophils of septic patients constitutively display, besides IL-10R2, also abundant levels of surface IL-10R1. Consequently, septic neutrophils are promptly responsive to IL-10 in vitro, as revealed by a direct IL-10-mediated induction of STAT3 tyrosine phosphorylation and SOCS-3 gene transcription, mRNA and protein expression. Consistent with the presence of a fully functional IL-10R, modulation of LPS-induced CXCL8, CCL4, tumour necrosis factor-alpha and IL-1ra gene expression was also rapidly induced by IL-10 in septic, but not normal, neutrophils. Collectively, these data uncover that neutrophils of septic patients are predisposed to be promptly responsive to IL-10, presumably to help limiting their pro-inflammatory state. They also fully validate our previous observations, herein in the context of a human disease, that responsiveness of human neutrophils to IL-10 is strictly dependent upon the modulation of IL-10R1 expression.