Contribution of Candida biomarkers and DNA detection for the diagnosis of invasive candidiasis in ICU patients with severe abdominal conditions.

BACKGROUND: To assess the performance of Candida albicans germ tube antibody (CAGTA), (1 → 3)-ß-D-glucan (BDG), mannan antigen (mannan-Ag), anti-mannan antibodies (mannan-Ab), and Candida DNA for diagnosing invasive candidiasis (IC) in ICU patients with severe abdominal conditions (SAC). METHODS: A prospective study of 233 non-neutropenic patients with SAC on ICU admission and expected stay ≥ 7 days. CAGTA (cutoff positivity ≥ 1/160), BDG (≥80, 100 and 200 pg/mL), mannan-Ag (≥60 pg/mL), mannan-Ab (≥10 UA/mL) were measured twice a week, and Candida DNA only in patients treated with systemic antifungals. IC diagnosis required positivities of two biomarkers in a single sample or positivities of any biomarker in two consecutive samples. Patients were classified as neither colonized nor infected (n = 48), Candida spp. colonization (n = 154) (low-grade, n = 130; high-grade, n = 24), and IC (n = 31) (intra-abdominal candidiasis, n = 20; candidemia, n = 11). RESULTS: The combination of CAGTA and BDG positivities in a single sample or at least one of the two biomarkers positive in two consecutive samples showed 90.3 % (95 % CI 74.2-98.0) sensitivity, 42.1 % (95 % CI 35.2-98.8) specificity, and 96.6 % (95 % CI 90.5-98.8) negative predictive value. BDG positivities in two consecutive samples had 76.7 % (95 % CI 57.7-90.1) sensitivity and 57.2 % (95 % CI 49.9-64.3) specificity. Mannan-Ag, mannan-Ab, and Candida DNA individually or combined showed a low discriminating capacity. CONCLUSIONS: Positive Candida albicans germ tube antibody and (1 → 3)-ß-D-glucan in a single blood sample or (1 → 3)-ß-D-glucan positivity in two consecutive blood samples allowed discriminating invasive candidiasis from Candida spp. colonization in critically ill patients with severe abdominal conditions. These findings may be helpful to tailor empirical antifungal therapy in this patient population.

ß-D-Glucan and Candida albicans germ tube antibody in ICU patients with invasive candidiasis.

PURPOSE: To assess the performance of (1→3)-ß-D-glucan (BDG) and Candida albicans germ tube antibody (CAGTA) for the diagnosis of invasive candidiasis (IC) in a prospective cohort of 107 unselected, non-neutropenic ICU patients. METHODS: BDG (cutoff positivity ≥80 pg/mL) and CAGTA (cutoff positivity ≥1/160) assays were performed twice a week. Confounding factors included amoxicillin-clavulanate and piperacillin-tazobactam treatments, recent surgery, Gram-positive bloodstream infection, renal replacement therapy, and enteral nutrition. Patients were classified as neither colonized nor infected (n = 29), Candida spp. colonization (n = 63) (low grade, n = 32; high grade, n = 31), and invasive candidiasis (IC) (n = 15). RESULTS: BDG levels were higher in patients with IC and high-grade colonization than in the remaining groups (p = 0.012), and two consecutive measurements ≥80 pg/mL discriminated IC from the remaining groups (sensitivity 80%, specificity 75.7%). For the discrimination between IC and Candida spp. colonization, the AUC for the maximum value of BDG was 0.667 (95% CI 0.544-0.790) and for the maximum value of CAGTA 0.545 (95% CI 0.395-0.694). Significant changes of BDG and CAGTA kinetics in IC patients treated with antifungals were not observed. In patients neither colonized nor infected or with low-grade Candida spp. colonization, none of the confounding factors was associated with a significant increase in BDG positivity. CONCLUSIONS: Two consecutive BDG levels ≥80 pg/mL allowed discrimination among IC and high-grade colonization. Systemic antifungal therapy could not be monitored with biomarker kinetics, and BDG levels were not subject to interference by confounding factors in either colonized or infected patients or with low-grade colonization.