Cerebrospinal Fluid and Plasma (1→3)-β-d-Glucan as Surrogate Markers for Detection and Monitoring of Therapeutic Response in Experimental Hematogenous Candida Meningoencephalitis▿
| Autor: | Diana Mickiene, John Bacher, William W. Hope, Vidmantas Petraitis, Margaret P. Cotton, Christine Mya-San, Johanna E. Hughes, Ruta Petraitiene, Thomas J. Walsh, Amy M. Kelaher, Heidi A. Murray |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2008 |
| Předmět: |
Pathology
medicine.medical_specialty Antifungal Agents beta-Glucans Biology Pharmacology Echinocandins Lipopeptides Cerebrospinal fluid Meningoencephalitis Amphotericin B Blood plasma medicine Animals Pharmacology (medical) Experimental Therapeutics Mycosis medicine.diagnostic_test Dose-Response Relationship Drug Micafungin Candidiasis medicine.disease Meningitis Fungal Disease Models Animal Infectious Diseases Therapeutic drug monitoring Female Rabbits Drug Monitoring Meningitis Biomarkers medicine.drug |
| Popis: | The treatment, diagnosis and therapeutic monitoring of hematogenousCandidameningoencephalitis (HCME) are not well understood. We therefore studied the expression of (1→3)-β-d-glucan (β-glucan) 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 (102to 103CFU/ml), spinal cord, and meninges (10 to 102CFU/g), only 8.1% of UC CSF cultures were positive. By comparison, all 25 UC CSF samples tested for β-glucan were positive (755 to 7,750 pg/ml) (P< 0.001). 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 ofCandida albicansfrom blood cultures was not predictive of eradication of organisms from the CNS; conversely, β-glucan levels in CSF were predictive of the therapeutic response. A significant decrease of β-glucan concentrations in CSF, in comparison to that for UC, started at 0.5 mg/kg (P< 0.001). Levels of plasma β-glucan were lower than levels in simultaneously obtained CSF (P< 0.05). CSF β-glucan levels correlated in a dose-dependent pattern with therapeutic responses and withCandidainfection in cerebral tissue (r= 0.842). Micafungin demonstrated dose-dependent and site-dependent activity against HCME. CSF β-glucan may be a useful biomarker for detection and monitoring of therapeutic response in HCME. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|