Testing of Cerebrospinal Fluid 1,3 Beta-D-Glucan for the Diagnosis of Fungal Meningitis Associated with Contaminated Methylprednisolone Injections

Background:

The prompt diagnosis and treatment of fungal meningitis is critical, but culture is insensitive.  (1,3)-beta-D-glucan (BDG) is FDA-cleared for serologic diagnosis of invasive fungal disease.  (Fungitell assay, Associates of Cape Cod Incorporated).  However, BDG is not cleared for testing cerebrospinal fluid (CSF) and the appropriate cutoff is unknown.  We aim to validate the accuracy of CSF BDG for the diagnosis of fungal meningitis among patients exposed to contaminated methylprednisolone acetate (MPA).        

Methods:

A case-control study was conducted at St. Joseph Mercy Hospital and Vanderbilt University from November, 2013 – February, 2014.  Patients were included if they received a contaminated MPA injection.  Cases were classified as probable or confirmed meningitis according to Centers for Disease Control and Prevention guidelines.  Controls were defined as persons exposed but not diagnosed with disease.  CSF BDG testing was performed according to the package insert for serum and validated using Clinical Laboratory Standards Institute procedures (MiraVista Diagnostics).

Results:

Of 233 patients, 45 had meningitis (28 confirmed), 53 had spinal/paraspinal infection (19 confirmed), and 135 did not develop disease.  The figure depicts CSF BDG results from those with confirmed meningitis, probable meningitis, and controls.  Using the manufacturer's cutoff (BDG ≥ 80 pg/mL), the sensitivity and specificity were 96% (95% CI 80-100%) and 93% (95% CI 87-97%) for confirmed meningitis and 84% (95% CI 70-93%) and 93% (95% CI 87-97%) for probable meningitis.  The Receiver Operating Characteristic analysis identified the optimal cutoff for confirmed meningitis to be ≥ 500 pg/mL (sensitivity 93% [95% CI 76-99%], specificity 100% [95% CI 97-100%]); for probable meningitis to be 66 pg/mL (sensitivity 91% [95% CI 79-98%],specificity 92% [95% CI 87-96%]).

Conclusion:

Our results suggest that CSF BDG is both a highly sensitive and specific test for diagnosis of fungal meningitis associated with contaminated MPA injections.  Further study is needed on the diagnostic utility of CSF BDG for other types of fungal meningitis.