Novel Biomarker in Invasive Candidiasis/Candida Sepsis

Invasive fungal infections including Candida infections are serious complications in immunocompromised patients but occur also in patients treated in ICUs. Survival rate of invasive Candida infections is associated with early initiation of antifungal therapy (15% mortality rate on day 0 related to the culture date of the first blood sample positive for yeasts compared to 41% for patients with 72 hours delayed antifungal therapy). Up to date, no laboratory method or clinical decision rule is available to anticipate invasive candidiasis and initiate antifungal therapy earlier. Actually culture based methods (e.g. blood cultures) miss up to 50% of invasive candidiasis cases. Antifungal therapy is therefore often administered without clear evidence of fungal infection. This approach does not lead to survival benefit but to increased selective pressure for the development of resistance to antifungal agents, potential risk of adverse drug reactions, and increased costs (expenses for antifungal therapy now account for half of the antimicrobial medication budget in large hospitals). The aim of our study is to identify biological markers to anticipate or support the diagnosis of invasive candidiasis in ICU patients, to overcome current deficiencies in detection of invasive candidiasis and consequently to differentiate between Candida spp. colonization and invasive Candida infection. We will investigate patients with confirmed invasive fungal infection, patients with Candida colonization and compared this patients with invasive bacterial infections and healthy controls. We will examine various biomarkers in patients blood and other fluid or tissue samples derived from patients and fungi. These biomarker should subsequently allow assignment of patients with risk of invasive fungal infection to patient groups with true invasive fungal infection or not. Our study should contribute to improved assessment of ICU patients at risk for invasive candidiasis and to improved diagnosis of invasive candidiasis. In clinical practice the reliable differentiation between infection and colonization will allow more targeted antifungal therapy leading to enhanced antifungal treatment initiation on the one hand (in cases of true invasive candidiasis) and to reduction of unnecessary antifungal treatments and treatment costs on the other hand.

Invasive Candida infections are serious complications in immunocompromised patients including those undergoing treatment for cancer but occur also in patients treated in ICUs. Survival rate of invasive candidiasis is associated with early initiation of antifungal therapy (15% mortality rate for candidemic patients with antifungal therapy on day 0 related to the culture date of the first blood sample positive for yeasts compared to 41% for patients who received antifungal therapy on day 3). Up to date, no laboratory method or clinical decision rule is available for correct anticipation of invasive candidiasis which would avoid delays in appropriate antifungal therapy initiation. The aim of our study was to identify biological markers to anticipate or support the diagnosis of invasive candidiasis in ICU patients, to overcome current deficiencies in detection of invasive candidiasis and consequently to differentiate between Candida spp. colonization and invasive Candida infection. We included patients with invasive fungal infections, patients with candida colonization, and as comparators patients with invasive bacterial infections as well as healthy subjects. We measured at multiple time points several biomarkers in blood and body fluids. We were able to show, that 1.the length of ICU stay and number of antibiotics administered during the ICU stay were associated with loss of bacterial diversity in all investigated body sites and that Candida spp. dominated fungal communities of all investigated body regions (pharynx, deep tracheal/bronchial secretion, gastric secretion, stool, feces or perianal swabs in intestinal paralysis) 2. the beta- D- Glucan tests in the perioperative setting up to 5 days postsurgery seems to be limited due to beta- D- Glucan elevations from intestinal surgical procedures 3. T2Candida might be valuable as an additional tool for the detection of invasive candida infection but does not replace blood cultures 4. interleukin- 17A, an inflammatory signal molecule, has no discriminative competence between fungal and bacterial infections and may be valuable as a biomarker for either fungal or bacterial blood stream infection rather than solely for invasive Candida infection 5.TGF-ß, another inflammatory signal molecule, was significantly elevated in patients with invasive candidiasis compared to bacteremic patients, proposing a potential significance of TGF-ß for differentiation between bacterial and Candida infections 6.qPCR of human circular DNA might has potential for the detection of invasive candida infection/candida sepsis but has to be further investigated regarding the discriminative potential