Reappraisal of the Serum (1→3)‐β‐D‐Glucan Assay for the Diagnosis of Invasive Fungal Infections—A Study Based on Autopsy Cases from 6 Years

Abstract

BACKGROUND: The prevalence of invasive fungal infection is increasing. An effective diagnostic test is required to identify and treat them successfully. METHODS: All autopsy records at our hospital for the period from January 2000 through December 2005 [corrected] were reviewed for cases of invasive fungal infection. The diagnostic efficacy of a serum (1-->3)-beta-D-glucan (beta-glucan) assay was examined using only those cases in which patients had been tested for fungal infection within 2 weeks before death. RESULTS: Of 456 autopsies, 54 (11.8%) involved cases of invasive fungal infection. Leukemias were the most frequent underlying disease (in 52% of cases of invasive fungal infection), and Aspergillus species was the most frequent pathogen detected (in 70%). Of the 54 patients with invasive fungal infection, 41 had beta-glucan testing performed within 2 weeks before death, as did 63 patients without invasive fungal infection; 48 of 54 patients with invasive fungal infection had a blood culture performed. The sensitivity and specificity of the beta-glucan test for the detection of invasive fungal infection were 95.1% and 85.7%, respectively, with a cutoff value of 30 pg/mL; 85.4% and 95.2%, respectively, with a cutoff value of 60 pg/mL; and 78.0% and 98.4%, respectively, with a cutoff value of 80 pg/mL. The sensitivity of blood culture testing was 8.3%. With a prevalence of 11.8%, the positive and negative predictive values for the beta-glucan test were 47.1% and 99.2%, respectively, with a cutoff of 30 pg/mL; 70.4% and 98.0%, respectively, with a cutoff of 60 pg/mL; and 86.7% and 97.1%, respectively, with a cutoff of 80 pg/mL. During the 6-year period studied, of 21 patients with fungus-positive blood cultures that were preceded or followed by a beta-glucan test within 2 weeks, 4 had negative beta-glucan test results (beta-glucan level, <30 pg/mL), and 17 had positive results (beta-glucan level, >60 pg/mL); the concordance between culture results and beta-glucan test results was 81.0%. Contrary to the general belief, 5 of 6 cases of cryptococcemia were associated with high serum beta-glucan levels. CONCLUSION: The beta-glucan test is an effective diagnostic tool for invasive fungal infection.