Cerebrospinal Fluid and Plasma (1-3)-β-D-Glucan as Surrogate Markers for Detection and Monitoring of Therapeutic Response in Experimental Hematogenous Candida Meningoencephalitis

• author:yirui
• date:2015-12-16
• click:

The treatment, diagnosis and therapeutic monitoring of hematogenous Candida meningoencephalitis (HCME) are not well understood. Scientist therefore studied the expression of (1-3)-β-D-glucan (BG) in cerebrospinal fluid (CSF) and plasma in a nonneutropenic rabbit model of experimental HCME treated with micafungin and amphotericin B. Groups studied consisted of micafungin (0.5 to 32 mg/kg) and amphotericin B (1 mg/kg) treatment groups and the untreated controls (UC). Despite well-established infection in the cerebrum, cerebellum, choroid, vitreous humor (102 to 103 CFU/ml), spinal cord, and meninges (10 to 102 CFU/g), only 8.1% of UC CSF cultures were positive. By comparison, all 25 UC CSF samples tested for BG were positive (755 to 7,750 pg/ml).
The therapeutic response in CNS tissue was site dependent, with significant decreases of the fungal burden in the cerebrum and cerebellum starting at 8 mg/kg, in the meninges at 2 mg/kg, and in the vitreous humor at 4 mg/kg.
A dosage of 24 mg/kg was required to achieve a significant effect in the spinal cord and choroid. Clearance of Candida albicans from blood cultures was not predictive of eradication of organisms from the CNS; conversely, BG levels in CSF were predictive of the therapeutic response. A significant decrease of BG concentrations in CSF, in comparison to that for UC, started at 0.5 mg/kg (P < 0.001). Levels of plasma BG were lower than levels in simultaneously obtained CSF (P < 0.05). CSF BG levels correlated in a dose-dependent pattern with therapeutic responses and with Candida infection in cerebral tissue (r=0.842). Micafungin demonstrated dose-dependent and site-dependent activity against HCME. CSF BG may be a useful biomarker for detection and monitoring of therapeutic response in HCME.