Invasive fungal infections and (1,3)-β- d-glucan serum concentrations in long-term intensive care patients

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Invasive fungal infections are associated with high morbidity and increased mortality. This study was performed to assess the epidemiology of fungal infections and to determine (1,3)-beta-D-glucan serum concentrations in patients admitted to intensive care units (ICUs). Overall 197 patients were admitted to nine medical and surgical intensive care units (ICUs) at a 2200-bed university hospital during a 3-month period. Retrospectively, the patients were split into three groups: group A comprised 24 patients with proven invasive fungal infections admitted for a median of 40 days. Group B comprised 58 patients who were admitted to the ICU for 30 days but without fungal infection. One hundred and fifteen post-operative patients served as controls (group C). The levels of (1,3)-beta-D-glucan were monitored in all patients twice weekly during their ICU admittance. Average (1,3)-beta-D-glucan concentrations were significantly higher in the patients with fungal infections compared to group B and group C (median 44 vs. 22 and 12.9 pg/ml, respectively; p<0.001). For a serum (1,3)-beta-D-glucan level of 40 pg/ml, the sensitivity, the specificity, the positive predictive value, the negative predictive value, the area under the curve of the receiver operating characteristics (AUC ROC) curve, the likelihood ratio (LR)+ and LR- were 52.2, 75.9, 46.2, 80, 0.7, 2.16, and 0.63, respectively, on day 7. Patients in group A had bacterial infections significantly more often than patients in group B (p=0.003). The hospitalization before ICU admittance for group A was significantly longer than for groups B and C (median 19 (group A) vs. 6 (group B) vs. 10 (group C) days; p<0.05). Longer hospitalization and multiple bacterial infections were found to be the main risk factors for invasive fungal infections. Long-term ICU patients have elevated (1,3)-beta-D-glucan levels, not only due to invasive fungal infections, but also due to the serious underlying diseases and conditions, inter-current complications, and intensive care measures. Yet, persistently high serum levels of (1,3)-beta-D-glucan in ICU patients may be indicative of invasive fungal infections and warrant additional diagnostic efforts.