December 20, 2013
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Novel marker sensitive to diagnose fungal meningitis in outbreak

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Testing for (1-3)-beta-D-glucan using cerebrospinal fluid had high sensitivity and specificity for diagnosing fungal meningitis during an outbreak of the disease last year, CDC researchers reported in Clinical Infectious Diseases.

“[These data] provide a first step for evaluating the utility of [cerebrospinal fluid (1-3)-beta-D-glucan] as a marker for monitoring therapeutic response in patients affected by this outbreak,” the researchers wrote. “Our preliminary data suggest that [(1-3)-beta-D-glucan] may be a useful marker for measuring disease resolution or progression in this patient population.”

The multistate outbreak of fungal meningitis, which began in September 2012 and resulted in 751 cases and 64 deaths as of October 2013, is one of the largest recorded health care–associated outbreaks in the United States, the researchers wrote. It was linked to contaminated vials of injectable methylprednisolone acetate produced by the New England Compounding Center.

The researchers explored the use of (1-3)-beta-D-glucan (BDG) detected in cerebrospinal fluid (CSF) as a diagnostic marker and a tool to evaluate patients’ response to treatment in this outbreak. They selected a stratified random sample of 41 proven cases that had available CSF white blood cell data. The study also included 66 negative control samples of CSF. The researchers used the Fungitell assay (Associates of Cape Cod Inc.) to test CSF for BDG.

A cutoff value of 138 pg/mL had a sensitivity of 100% and a specificity of 98%. To measure the utility of BDG as a treatment response marker, levels of BDG were compared among 20 case patients who were divided into two groups. In group one, BDG levels remained >500 pg/mL, and in group two, BDG levels declined and remained <500 pg/mL.

Patients in group one had poor clinical outcomes: stroke (n=1), relapsed meningitis (n=2) or relapse with soft tissue phlegmon (n=1). Patients in group one all had a decline in BDG: Six patients remained above the 138 pg/mL cutoff and 10 declined to low levels ranging from 18 pg/mL to 128 pg/mL. Among the six who remained above the cutoff, five discontinued antifungal therapy and remain asymptomatic, and one continues to receive antifungal treatment because of white blood cell presence in CSF. Among the 10 patients who declined to low levels, nine patients discontinued antifungal therapy and remain asymptomatic.

Disclosure: The researchers report no relevant financial disclosures.