Utility of (1–3)-β-d-Glucan Testing for Diagnostics and Monitoring Response to Treatment During the Multistate Outbreak of Fungal Meningitis and Other Infections

Since September 2012, the Centers for Disease Control and Prevention (CDC), together with state and local health departments, has been investigating an outbreak of fungal meningitis and other infections associated with injection of contaminated methylprednisolone acetate (MPA) produced by the New England Compounding Center (NECC). By October 2013, 751 cases were identified with 64 deaths, making this one of the largest recorded healthcare-associated outbreaks in US history [1, 2]. Although several molds were isolated from cerebrospinal fluid (CSF) and tissues of case patients, Exserohilum rostratum has been the predominant pathogen [3, 4]. Invasive infection due to E. rostratum, a fungus found in soil associated with plants [5], is rare and has previously been described only in persons with impaired immune systems [6, 7]. Furthermore, until this outbreak no cases of meningitis or encephalitis caused by this fungus had been reported. As part of the response to this public health disaster, the CDC developed a rapid polymerase chain reaction (PCR) test for detection of fungal DNA in human fluids and tissues [8]. This assay is estimated to have 29% diagnostic sensitivity and 100% specificity. (1,3)-β-d-glucan (BDG) is a glucose polymer that is part of the fungal cell wall [9]. The Fungitell assay (Associates of Cape Cod, Inc, Falmouth, Massachusetts) has been approved by the US Food and Drug Administration (FDA) for detection of BDG in human serum and used in diagnosis of fungal infections [10–12]. The potential drawbacks of this assay include (1) inability to differentiate among fungal species causing infections, (2) cross-reactivity with certain bacteria and drugs, and (3) false positivity due to specimen contamination [10]. Therefore, results of this assay must be interpreted in combination with clinical and epidemiological findings. There are few data on the Fungitell assay using CSF in patients with fungal meningitis [13, 14]; one recent report using this assay in 5 patients from this outbreak demonstrated that 3 had elevated CSF levels of BDG [15]. Here, we explore BDG as a supplemental diagnostic marker for fungal meningitis in this outbreak, and assess its utility for evaluating patients' response to treatment.