(1,3)-β-d-Glucan-based empirical antifungal interruption in suspected invasive candidiasis: a randomized trial

Abstract

Background (1,3)-β-d-Glucan has been widely used in clinical practice for the diagnosis of invasive Candida infections. However, such serum biomarker showed potential to guide antimicrobial therapy in order to reduce the duration of empirical antifungal treatment in critically ill septic patients with suspected invasive candidiasis. Methods This was a single-centre, randomized, open-label clinical trial in which critically ill patients were enrolled during the admission to the intensive care unit (ICU). All septic patients who presented invasive Candida infection risk factors and for whom an empirical antifungal therapy was commenced were randomly assigned (1:1) in those stopping antifungal therapy if (1,3)-β-d-glucan was negative ((1,3)-β-d-glucan group) or those continuing the antifungal therapy based on clinical rules (control group). Serum 1,3-β-d-glucan was measured at the enrolment and every 48/72 h over 14 days afterwards. The primary endpoint was the duration of antifungal treatment in the first 30 days after enrolment. Results We randomized 108 patients into the (1,3)-β-d-glucan (n = 53) and control (n = 55) groups. Median [IQR] duration of antifungal treatment was 2 days [1–3] in the (1,3)-β-d-glucan group vs. 10 days [6–13] in the control group (between-group absolute difference in means, 6.29 days [95% CI 3.94–8.65], p < 0.001). Thirty-day mortality was similar (28.3% [(1,3)-β-d-glucan group] vs. 27.3% [control group], p = 0.92) as well as the overall rate of documented candidiasis (11.3% [(1,3)-β-d-glucan group] vs. 12.7% [control group], p = 0.94), the length of mechanical ventilation (p = 0.97) and ICU stay (p = 0.23). Conclusions In critically ill septic patients admitted to the ICU at risk of invasive candidiasis, a (1,3)-β-d-glucan-guided strategy could reduce the duration of empirical antifungal therapy. However, the safety of this algorithm needs to be confirmed in future, multicentre clinical trial with a larger population. Trial registration ClinicalTrials.gov, NCT03117439, retrospectively registered on 18 April 2017

A Ten-Year Retrospective Study of Invasive Candidiasis in a Tertiary Hospital

“…Further investigation during the follow-up showed 29.7% of the false negative results were due to insu cient increase compared to the threshold, and 14.8% were due to the lag in increase. Some studies previously suggested to use the negative results of BDG to exclude IC diagnosis and allow discontinuation of the empirical therapy [30,33,34]. However, this might delay the preemptive therapy as BDG in this study reacted slowly (averagely 3 days later) and rose insu ciently, which might cause falsenegativity.…”

Performance of Repeated Measures of (1–3)-β-D-Glucan, Mannan Antigen, and Antimannan Antibodies for the Diagnosis of Invasive Candidiasis in ICU Patients: A Preplanned Ancillary Analysis of the EMPIRICUS Randomized Clinical Trial

“…However, in a subgroup of a preselected population at risk of IC, the predictive positive value of the test increased. Two studies involving patients with sepsis and fungal colonization reported that a negative BDG could avoid the initiation of an antifungal treatment without increasing the risk of IFI and death [ 36 , 37 ].…”

Letter on “(1,3)-β-d-Glucan-based empirical antifungal interruption in suspected invasive candidiasis: a randomized trial”

“…The diagnostic criteria of IC, the proportion of candidemia versus non-candidemic IC, and most importantly, the targeted population of BDG testing and prevalence of the disease could influence diagnostic performances. In the present study, the PPV of BDG for IC diagnosis was 37% for a prevalence of IC of 12% [ 1 ]. We observed comparable results in a study reporting our experience of BDG testing in ICU (PPV 36%, IC prevalence 19%) [ 4 ].…”

“…To the Editor: De Pascale et al recently reported on the potential role of (1,3)-β- d -glucan (BDG)-guided strategy as an antifungal stewardship tool in patients with sepsis/septic shock and risk factors for invasive candidiasis (IC) [ 1 ]. This raises the question of the possible drawback of false-positive results, which may lead to antifungal treatment (AF) overconsumption.…”