title: 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.
abstract: BACKGROUND
  The 2012 outbreak of fungal meningitis associated with contaminated methylprednisolone produced by a compounding pharmacy has resulted in >750 infections. An important question facing patients and clinicians is the duration of antifungal therapy. We evaluated (1-3)-β-d-glucan (BDG) as a marker for monitoring response to treatment.
  
  
  METHODS
  We determined sensitivity and specificity of BDG testing using the Fungitell assay, by testing 41 cerebrospinal fluid (CSF) specimens from confirmed cases of fungal meningitis and 66 negative control CSF specimens. We also assessed whether BDG levels correlate with clinical status by using incident samples from 108 case patients with meningitis and 20 patients with serially collected CSF.
  
  
  RESULTS
  A cutoff value of 138 pg/mL provided 100% sensitivity and 98% specificity for diagnosis of fungal meningitis in this outbreak. Patients with serially collected CSF were divided into 2 groups: those in whom BDG levels declined with treatment and those in whom BDG remained elevated. Whereas most patients with a decline in CSF BDG had clinical improvement, all 3 patients with continually elevated BDG had poor clinical outcomes (stroke, meningitis relapse, or development of new disease).
  
  
  CONCLUSIONS
  Our data suggest that measuring BDG in CSF is a highly sensitive test for diagnosis of fungal meningitis in this outbreak. Analysis of BDG levels in serially collected CSF demonstrated that BDG may correlate with clinical response. Routine measurement of BDG in CSF may provide useful adjunctive data for the clinical management of patients with outbreak-associated meningitis.
authors: Mycotic Diseases Branch, National Center for Emerging and Zoonotic Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia.
authors: Anastasia P
authors: AP
authors: Litvintseva
authors: Mark D
authors: MD
authors: Lindsley
authors: Lalitha
authors: L
authors: Gade
authors: Rachel
authors: R
authors: Smith
authors: Tom
authors: T
authors: Chiller
authors: Jennifer L
authors: JL
authors: Lyons
authors: Kiran T
authors: KT
authors: Thakur
authors: Sean X
authors: SX
authors: Zhang
authors: Dale E
authors: DE
authors: Grgurich
authors: Thomas M
authors: TM
authors: Kerkering
authors: Mary E
authors: ME
authors: Brandt
authors: Benjamin J
authors: BJ
authors: Park
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D019411:Clinical Laboratory Techniques / Q000379:methods*; D003955:Diagnostic Tests, Routine / Q000379:methods*; D004196:Disease Outbreaks; D016903:Drug Monitoring / Q000379:methods*; D005260:Female; D006801:Humans; D008297:Male; D016921:Meningitis, Fungal / Q000175:diagnosis* / Q000453:epidemiology*; D008875:Middle Aged; D011509:Proteoglycans; D012680:Sensitivity and Specificity; D047071:beta-Glucans / Q000134:cerebrospinal fluid*
chemical_list: D011509:Proteoglycans; D047071:beta-Glucans; C010770:polysaccharide-K
keywords: (1-3)-β-d-glucan; Exserohilum; Fungitell; fungal meningitis