Clinical Information

Invasive fungal infections (IFI) due to opportunistic fungal pathogens are a significant cause of morbidity and mortality, particularly among patients who are significantly immunosuppressed, including hematopoietic stem cell transplant recipients, solid organ transplant recipients, and those with hematologic or immune deficiencies. Patient recovery and survival following an IFI are directly related to the timely clinical recognition and prompt administration of antifungal therapy. Laboratory diagnosis of IFI is largely based on direct microscopic examination of patient specimens, histopathologic examination of tissue biopsies, isolation of fungi via culture, and, more recently, through molecular methods. However, these techniques commonly require invasive sample collection methods (eg, biopsy, bronchoalveolar lavage), which may be contraindicated in certain patients. Additionally, both microscopy and culture are frequently insensitive, with prior studies showing the sensitivity of culture for invasive Aspergillus infections ranges from 40% to 85%, and some fungi require prolonged incubation times, limiting the utility of culture in the acute patient setting. Due to these limitations, use of fungal biomarkers, including detection of (1,3)-beta-D-glucan (BDG), have emerged as useful adjunct tests available for detection of IFI.

(1,3)-beta-D-glucan is found in the cell walls of most fungi (eg, Candida, Aspergillus, Fusarium, Pneumocystis jirovecii) with the notable exception of Cryptococcus species, Blastomyces species, and the Mucorales (eg, Lichtheimia, Mucor, Rhizopus), which either lack BDG entirely or produce it in very low amounts. Elevated serum BDG levels have been associated with the presence of a fungal infection. The BDG levels may be detected prior to the development of clinical symptoms and before isolation or identification of the fungal organism via routine methods. The sensitivity and specificity of BDG detection in patients with proven or probable IFI range from 64% to 93% and 87% to 100%, respectively, among different studies.

Importantly, the BDG assay should not be used alone to diagnose an IFI but rather in conjunction with careful evaluation of patient risk factors for infection, other laboratory testing, and radiologic findings.