Fungal Infections in Patients with Septic Shock

Sepsis is most frequently a result of a bacterial infection, with those of a fungal nature less common. Nevertheless, many patients may develop a fungal colonization during hospitalisation, resulting in a mixed bacterial and fungal infection. Indeed, Elke et al. (2018) found that close to 30% of patients upon sepsis diagnosis had some sort of fungal infection in addition to the presence of a Gram positive and/or negative bacterial infection.

Only a small proportion of affected patients show positive blood cultures, and fungal growth on culture media is known to be very slow Ref-1, with the delayed or lack of administration of antifungal therapy associated with an increased mortality rate Ref-2-4.

In a recent investigation, Decker et al. (2017) compared the diagnostic value of numerous biomarkers and cytokines in septic shock patients with a fungal infection, as well as analysing the overall host response by expression profiling of Candida spp.-infected epithelia in vitro.

Compared to established fungal biomarkers such as (1,3)-β-D-Glucan (BG) and Galactomannan (GM), MR-proADM could accurately distinguish between patients with invasive fungal infections from those with no fungal findings at all time points, with higher median concentrations in patients with invasive fungal infections compared to those with fungal colonizations.

Using reconstituted human epithelia infected with two different fungal species – C. albicans and C. dubliniensis, C. albicans immediately started forming hyphae and penetrating the epithelia whilst C. dubliniensis remained in yeast form adhering to the epithelia but not penetrating it. The adrenomedullin (ADM) gene was found to have the strongest transcriptional activation in response to both fungi, and may therefore be a far earlier diagnostic biomarker for fungal infections on epithelia compared to the other cytokines or interleukins.

Figure 1. Early transcriptional host response to a fungal colonisation of vulvovaginal reconstituted human epithelia. (A) Hierarchical clustering of 21 differentially expressed genes based on their fold changes from an uninfected control. (B) Expression values of late-stage Candida-induced cytokines compared to ADM.Figure 1. Early transcriptional host response to a fungal colonisation of vulvovaginal reconstituted human epithelia. (A) Hierarchical clustering of 21 differentially expressed genes based on their fold changes from an uninfected control. (B) Expression values of late-stage Candida-induced cytokines compared to ADM.

References Fungal infections in patients with septic shock

Ref-1: Decker SO, Sigl A, Grumaz C, et al. Immune-Response Patterns and Next Generation Sequencing Diagnostics for the Detection of Mycoses in Patients with Septic Shock-Results of a Combined Clinical and Experimental Investigation. Int J Mol Sci. 2017;18(8).

Ref-2: Bassetti M, Righi E, Ansaldi F, et al. A multicenter study of septic shock due to candidemia: outcomes and predictors of mortality. Intensive Care Med. 2014;40(6):839-845.

Ref-3: Abe M, Kimura M, Araoka H, Taniguchi S, Yoneyama A. Is initial serum (1,3)-beta-d-glucan truly associated with mortality in patients with candidaemia? Clin Microbiol Infect. 2016;22(6):576.

Ref-4: Garey KW, Rege M, Pai MP, et al. Time to initiation of fluconazole therapy impacts mortality in patients with candidemia: a multi-institutional study. Clin Infect Dis. 2006;43(1):25-31.

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