Efficacy of Cerebrospinal Fluid Beta-d-Glucan Diagnostic Testing for Fungal Meningitis: a Systematic Review

Background: Several case reports and cohort studies have examined the use of (1, 3) beta-D-glucan in cerebrospinal fluid to diagnose fungal meningitis. This systematic review aims to characterize the evidence regarding cerebrospinal fluid (1, 3) beta-D-glucan measurement to detect fungal meningitis. Methods: We searched PubMed for (1, 3) beta-D-glucan and each of several distinct fungi, cerebrospinal fluid, and meningitis. Summary data including diagnostic performance (where applicable) was recorded. Findings: 939 records were examined via PubMed search. 118 remained after duplicates were removed and 104 records were excluded as they did not examine cerebrospinal fluid, included animals, or focused on non-fungal infections. 14 studies were included in this systematic review. A variety of fungi including Candida, Aspergillus, Exserohilum, Cryptococcus, Histoplasma, and Coccidioides were studied, although most were case reports. Diagnostic accuracy was examined in 5 studies. CSF (1, 3) beta-D-glucan showed > 95% sensitivity in the corticosteroid injection related outbreak of Exserohilum rostratum. One study in Histoplasma meningitis found 53% (53/87) sensitivity and 87% (133/153) specificity while another study of Cryptococcus meningitis found 89% (69/78) sensitivity and 85% (33/39) specificity. Interpretation: CSF (1, 3) beta-D-glucan testing may be useful, primarily as a non-specific marker of fungal meningitis. Although the FDA black box warning states that Cryptococcus does not make (1, 3) beta-D-glucan, the current evidence shows that (1, 3) beta-D-glucan is detectable in cryptococcal meningitis. Organism specific testing should be used in conjunction with (1, 3) beta-D-glucan. Funding: National Institute of Neurologic Disorders and Stroke of the National Institutes of Health Award Numbers K23NS110470 and R01NS086312.