(511) A Proinflammatory Cytokine Response Correlates With Protection From Candida Gut Colonization

Introduction: Candida spp. are the second most common cause of intensive care unit (ICU)-onset bloodstream infection (BSI). Candida gut colonization is a key step in the development of Candida BSI but factors that influence Candida gut colonization are unknown. We determined the relationship between Candida gut colonization and host immune response in the ICU.

Methods: We prospectively enrolled patients admitted to any ICU at a tertiary care hospital and collected stool and blood samples for up to four weeks or until ICU discharge. Stool samples were plated on CHROMagar Candida Plus. Cytokine levels from plasma collected within two days of a stool sample were determined with the MILLIPEX Human Cytokine/Chemokine/Growth Factor Panel A. Using Mann-Whitney or Wilcoxon tests we compared cytokine levels between plasma that corresponded to stool with vs. without Candida colonization.

Results: We included 13 patients (median age 64 [IQR 61-68], and 5 [38%] female). Patients were most commonly in the medical (4/13; 31%) or neurological (4/13; 31%) ICU; 4 (31%) were in shock on ICU admission; 11 (85%) required mechanical ventilation; and 2 (15%) died in the hospital. These 13 patients provided 25 paired stool/plasma samples, of which 13 (52%) stool samples had Candida colonization (most commonly with C. glabrata [69% of colonized samples]). Compared to plasma corresponding with Candida-colonized stool samples, non-colonized samples had higher median pro-inflammatory cytokine levels including IFN-γ (1.0 vs. 0.0, p=0.04), IL-12(p70) (4.2 vs. 0.4, p=0.01), and numerically higher levels of IL-1β (3.2 vs. 0.0, p=0.08), IL-6 (84.0 vs. 27.3, p=0.08), and IL-9 (33.4 vs. 10.4, p=0.06) (all in pg/mL). There was no difference in IL-17 or IL-22 levels. When restricted to 8 samples among 4 patients who gained/lost Candida colonization, IL-6 levels were numerically higher among non-colonized samples (105.0 vs. 8.6 pg/mL, p=0.11).

Conclusions: In a mixed ICU population, a pro-inflammatory cytokine signature correlated with protection from Candida gut colonization. Further research is needed to determine whether microbiome composition, Candida-immune interactions, or other factors drive these changes. These results may facilitate discovery of novel therapeutics to prevent Candida gut colonization and candidemia in ICU patients.