Abstract
BackgroundInvasive fungal infections (IFI) are difficult to diagnose, especially in critically ill patients. As the mannose receptor (MR) is shed from macrophage cell surfaces after exposure to fungi, we investigate whether its soluble serum form (sMR) can serve as a biomarker of IFI.MethodsThis is a secondary analysis of the multicentre randomised controlled trial (EPaNIC, n = 4640) that investigated the impact of initiating supplemental parenteral nutrition (PN) early during critical illness (Early-PN) as compared to withholding it in the first week of intensive care (Late-PN). Serum sMR concentrations were measured in three matched patient groups (proven/probable IFI, n = 82; bacterial infection, n = 80; non-infectious inflammation, n = 77) on the day of antimicrobial initiation or matched intensive care unit day and the five preceding days, as well as in matched healthy controls (n = 59). Independent determinants of sMR concentration were identified via multivariable linear regression. Serum sMR time profiles were analysed with repeated-measures ANOVA. Predictive properties were assessed via area under the receiver operating curve (aROC).ResultsSerum sMR was higher in IFI patients than in all other groups (all p < 0.02), aROC to differentiate IFI from no IFI being 0.65 (p < 0.001). The ability of serum sMR to discriminate infectious from non-infectious inflammation was better with an aROC of 0.68 (p < 0.001). The sMR concentrations were already elevated up to 5 days before antimicrobial initiation and remained stable over time. Multivariable linear regression analysis showed that an infection or an IFI, higher severity of illness and sepsis upon admission were associated with higher sMR levels; urgent admission and Late-PN were independently associated with lower sMR concentrations.ConclusionSerum sMR concentrations were higher in critically ill patients with IFI than in those with a bacterial infection or with non-infectious inflammation. However, test properties were insufficient for diagnostic purposes.
Highlights
Invasive fungal infections (IFI) are difficult to diagnose, especially in critically ill patients
The highest serum serum form (sMR) concentrations were observed for patients with proven invasive aspergillosis (1.20 (0.57–1.51) mg/L) and for patients with candidaemia (1.14 (0.67–1.81) mg/L) (Table 2)
The sMR serum concentrations for different sites of bacterial infections are available in the supplemental information (Additional file 1)
Summary
Invasive fungal infections (IFI) are difficult to diagnose, especially in critically ill patients. Invasive fungal infections (IFI) have emerged in this population and have been associated with an increased morbidity and mortality [1, 2]. Classical diagnostic tools such as culture and biopsy are invasive and time-consuming and show low sensitivity [4]. Biomarkers, such as serum fungal cell wall components, can be detected rapidly but have a variable sensitivity and a low specificity, especially in intensive care unit (ICU) patients [4, 5]. There is an increasing need for novel and accurate diagnostic tools for IFI during critical illness
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