title: (1,3)-β-d-glucan in cerebrospinal fluid for diagnosis of fungal meningitis associated with contaminated methylprednisolone injections.
abstract: Prompt diagnosis and treatment of fungal meningitis are critical, but culture is insensitive. (1,3)-β-d-Glucan (BDG) testing is FDA approved for serological diagnosis of invasive fungal disease; however, BDG testing is not approved for cerebrospinal fluid (CSF), and the appropriate cutoff value is unknown. We aimed to validate the diagnostic accuracy of CSF BDG measurements for fungal meningitis among patients exposed to contaminated methylprednisolone acetate (MPA). A retrospective observational study was conducted at St. Joseph Mercy Hospital and Vanderbilt University from November 2013 to February 2014. Patients were included if they had received a contaminated MPA injection. Cases were classified as probable or proven meningitis according to Centers for Disease Control and Prevention guidelines. CSF BDG testing was performed according to the package insert instructions for serum samples, and results were validated using Clinical and Laboratory Standards Institute procedures (MiraVista Diagnostics). Of 233 patients, 45 had meningitis (28 proven cases), 53 had spinal/paraspinal infections (19 proven cases), and 135 did not develop disease. Using the manufacturer's cutoff value (≥80 pg/ml), the sensitivity and specificity were 96% and 95%, respectively, for proven meningitis and 84% and 95% for probable or proven meningitis. Receiver operating characteristic analysis identified the optimal cutoff value for proven meningitis to be 66 pg/ml (sensitivity, 100%; specificity, 94%) and that for probable or proven meningitis to be 66 pg/ml (sensitivity, 91%; specificity, 92%). Our results suggest that CSF BDG measurements are highly sensitive and specific for the diagnosis of fungal meningitis associated with contaminated MPA injections. Further study on the utility of CSF BDG testing for other types of fungal meningitis is needed.
authors.affiliation: Department of Medicine, Section of Infectious Diseases, St. Joseph Mercy Hospital, Ann Arbor, Michigan, USA anurag.malani@stjoeshealth.org.
authors.forename: Anurag N
authors.initials: AN
authors.lastname: Malani
authors.affiliation: Department of Clinical Research, St. Joseph Mercy Hospital, Ann Arbor, Michigan, USA.
authors.forename: Bonita
authors.initials: B
authors.lastname: Singal
authors.affiliation: MiraVista Diagnostics, Indianapolis, Indiana, USA.
authors.forename: L Joseph
authors.initials: LJ
authors.lastname: Wheat
authors.affiliation: Department of Medicine, St. Joseph Mercy Hospital, Ann Arbor, Michigan, USA.
authors.forename: Ola
authors.initials: O
authors.lastname: Al Sous
authors.affiliation: MiraVista Diagnostics, Indianapolis, Indiana, USA.
authors.forename: Theresa A
authors.initials: TA
authors.lastname: Summons
authors.affiliation: MiraVista Diagnostics, Indianapolis, Indiana, USA.
authors.forename: Michelle M
authors.initials: MM
authors.lastname: Durkin
authors.affiliation: Department of Medicine, Division of Infectious Diseases, Vanderbilt University School of Medicine, Nashville, Tennessee, USA.
authors.forename: April C
authors.initials: AC
authors.lastname: Pettit
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000134:cerebrospinal fluid; D002555:Cerebrospinal Fluid / Q000737:chemistry*; D019411:Clinical Laboratory Techniques / Q000379:methods*; D004340:Drug Contamination; D005260:Female; D006801:Humans; D007267:Injections / Q000009:adverse effects; D008297:Male; D016921:Meningitis, Fungal / Q000175:diagnosis*; D008775:Methylprednisolone / Q000008:administration & dosage / Q000009:adverse effects; D008875:Middle Aged; D011509:Proteoglycans; D012372:ROC Curve; D012189:Retrospective Studies; D012680:Sensitivity and Specificity; D047071:beta-Glucans / Q000134:cerebrospinal fluid*
chemical_list: D015415:Biomarkers; D011509:Proteoglycans; D047071:beta-Glucans; C010770:polysaccharide-K; D008775:Methylprednisolone