Mycoses in patients with septic shock

Fungi are of increasing importance in sepsis. However, culture-based diagnostic procedures are associated with relevant weaknesses. Therefore, culture- and NGS-based fungal findings as well as corresponding plasma levels of BG, INF-?, TNF-a, IL-2, -4, -6, -10, -17A and MR-proADM were evaluated in 50 septic patients at 6 consecutive time points within 28 days after sepsis onset. Moreover, immune-response patterns during infections with Candida spp. were studied in a reconstituted human epithelium model. In total, 22% (n=11) of patients suffered from a fungal infection. A NGS-based diagnostic approach appeared to be suitable for the identification of fungal pathogens in patients suffering from fungemia as well as in patients with negative blood cultures. Moreover, MR-proADM and IL-17A in plasma proved suitable for the identification of patients with a fungal infection. Using RNA-seq., adrenomedullin (ADM) was shown to be a target gene, which is upregulated early after an epithelial infection with Candida spp.. In summary, a NGS-based diagnostic approach is able to close the diagnostic gap of routinely used culture-based diagnostic procedures, which can be further facilitated by plasmatic measurements of IL-17A as well as MR-proADM. Moreover, ADM was identified as an early target gene in response to epithelial infections with Candida spp..