Cerebrospinal Fluid and Plasma (1→3)-β- d -Glucan as Surrogate Markers for Detection and Monitoring of Therapeutic Response in Experimental HematogenousCandidaMeningoencephalitis

作者：Rūta Petraitienė, Vidmantas Petraitis, William Hope, Diana Mickiene, Amy M. Kelaher, Heidi Murray‐Smith, Christine Mya-San, Johanna E. Hughes, Margaret P. Cotton, John Bacher, Thomas J. Walsh · 发表于：Antimicrobial Agents and Chemotherapy · 年份：2008 · DOI：10.1128/aac.00674-08 · 被引用次数：63 · 研究领域：Antifungal resistance and susceptibility、Fungal Infections and Studies、Bacterial Infections and Vaccines

The treatment, diagnosis and therapeutic monitoring of hematogenous Candida meningoencephalitis (HCME) are not well understood. We therefore studied the expression of (1-->3)-beta-D-glucan (beta-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 (10(2) to 10(3) CFU/ml), spinal cord, and meninges (10 to 10(2) CFU/g), only 8.1% of UC CSF cultures were positive. By comparison, all 25 UC CSF samples tested for beta-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 of Candida albicans from blood cultures was not predictive of eradication of organisms from the CNS; conversely, beta-glucan levels in CSF were predictive of the therapeutic response. A significant decrease of beta-glucan concentrations in CSF, in comparison to that for UC, started at 0.5 mg/kg (P < 0.001). Levels of plasma beta-glucan were lower than levels in simultaneously...