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

Abstract

BackgroundTo 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).MethodsA 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).ResultsThe 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.ConclusionsPositive 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.

A New Age in Molecular Diagnostics for Invasive Fungal Disease: Are We Ready?

“…PCR performance data for forms of IC other than candidemia are relatively limited -for intra-abdominal candidiasis, PCR sensitivities of 86-91% have been reported for the species targeted, but specificity varies widely (33-97%) Fortún et al, 2014;León et al, 2016;Clancy and Nguyen, 2018b). Nguyen et al (2012) found a Candida real-time PCR assay to be more sensitive than the Fungitell R 1,3-β-D glucan (BDG) assay (Associates of Cape Cod, United States) for diagnosis of all IC (80 versus 56%) as well as deep seated (blood culture negative) candidiasis (89 versus 53%).…”

Evaluation of the Use of Novel Biomarkers to Augment Antimicrobial Stewardship Program Activities

“…In one study of 107 ICU patients, two or more serial BDG levels of 80 pg/ml in consecutive measurements obtained 24–48 hours apart resulted in a sensitivity of 80%, specificity of 75%, and strong negative predictive value of 95.9% (89.3%–98.5%) for candidemia . Multiple studies confirm improvement in BDG performance when serial measurements are used …”

“…Given the potential for false positive results, some investigators have proposed serial BDG measurements and use in combination with other tests to improve performance for diagnosis of IC . In one study of 107 ICU patients, two or more serial BDG levels of 80 pg/ml in consecutive measurements obtained 24–48 hours apart resulted in a sensitivity of 80%, specificity of 75%, and strong negative predictive value of 95.9% (89.3%–98.5%) for candidemia .…”

Diagnosis of Invasive Candidiasis: From Gold Standard Methods to Promising Leading-edge Technologies

“…The diagnostic performance of several human proteins involved in the immune response against infection (other than antibodies) and inflammation has also been investigated in patients at risk for IC [61,65,103,[113][114][115]. In particular, procalcitonin (PCT), serum amyloid A (SAA), interleukin 17 (IL17), interleukin 23 (IL23) and transforming growth factor ß (TGF-ß), among other acute phase proteins and pro-inflammatory cytokines, have been reported as potential diagnostic biomarkers for IC [61,103,113,115]. However, these host-derived biomarker candidates have not yet proven to be sufficiently accurate to reach widespread clinical use on their own, nor have they been validated in large multicenter clinical studies [61,65,103].…”