{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,11]],"date-time":"2026-02-11T02:44:43Z","timestamp":1770777883091,"version":"3.50.0"},"reference-count":35,"publisher":"American Society for Microbiology","issue":"11","license":[{"start":{"date-parts":[[2008,11,1]],"date-time":"2008-11-01T00:00:00Z","timestamp":1225497600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[2008,11]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>The treatment, diagnosis and therapeutic monitoring of hematogenous<jats:italic>Candida<\/jats:italic>meningoencephalitis (HCME) are not well understood. We therefore studied the expression of (1\u21923)-\u03b2-<jats:sc>d<\/jats:sc>-glucan (\u03b2-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<jats:sup>2<\/jats:sup>to 10<jats:sup>3<\/jats:sup>CFU\/ml), spinal cord, and meninges (10 to 10<jats:sup>2<\/jats:sup>CFU\/g), only 8.1% of UC CSF cultures were positive. By comparison, all 25 UC CSF samples tested for \u03b2-glucan were positive (755 to 7,750 pg\/ml) (<jats:italic>P<\/jats:italic>&lt; 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<jats:italic>Candida albicans<\/jats:italic>from blood cultures was not predictive of eradication of organisms from the CNS; conversely, \u03b2-glucan levels in CSF were predictive of the therapeutic response. A significant decrease of \u03b2-glucan concentrations in CSF, in comparison to that for UC, started at 0.5 mg\/kg (<jats:italic>P<\/jats:italic>&lt; 0.001). Levels of plasma \u03b2-glucan were lower than levels in simultaneously obtained CSF (<jats:italic>P<\/jats:italic>&lt; 0.05). CSF \u03b2-glucan levels correlated in a dose-dependent pattern with therapeutic responses and with<jats:italic>Candida<\/jats:italic>infection in cerebral tissue (<jats:italic>r<\/jats:italic>= 0.842). Micafungin demonstrated dose-dependent and site-dependent activity against HCME. CSF \u03b2-glucan may be a useful biomarker for detection and monitoring of therapeutic response in HCME.<\/jats:p>","DOI":"10.1128\/aac.00674-08","type":"journal-article","created":{"date-parts":[[2008,9,9]],"date-time":"2008-09-09T00:34:23Z","timestamp":1220920463000},"page":"4121-4129","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":58,"title":["Cerebrospinal Fluid and Plasma (1\u21923)-\u03b2-<scp>d<\/scp>-Glucan as Surrogate Markers for Detection and Monitoring of Therapeutic Response in Experimental Hematogenous<i>Candida<\/i>Meningoencephalitis"],"prefix":"10.1128","volume":"52","author":[{"given":"Ruta","family":"Petraitiene","sequence":"first","affiliation":[{"name":"Immunocompromised Host Section, Pediatric Oncology Branch, National Cancer Institute, Bethesda"},{"name":"Laboratory Animal Sciences Program, SAIC-Frederick, Inc., Frederick"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vidmantas","family":"Petraitis","sequence":"additional","affiliation":[{"name":"Immunocompromised Host Section, Pediatric Oncology Branch, National Cancer Institute, Bethesda"},{"name":"Laboratory Animal Sciences Program, SAIC-Frederick, Inc., Frederick"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"William W.","family":"Hope","sequence":"additional","affiliation":[{"name":"Immunocompromised Host Section, Pediatric Oncology Branch, National Cancer Institute, Bethesda"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Diana","family":"Mickiene","sequence":"additional","affiliation":[{"name":"Immunocompromised Host Section, Pediatric Oncology Branch, National Cancer Institute, Bethesda"},{"name":"Laboratory Animal Sciences Program, SAIC-Frederick, Inc., Frederick"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amy M.","family":"Kelaher","sequence":"additional","affiliation":[{"name":"Immunocompromised Host Section, Pediatric Oncology Branch, National Cancer Institute, Bethesda"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Heidi A.","family":"Murray","sequence":"additional","affiliation":[{"name":"Immunocompromised Host Section, Pediatric Oncology Branch, National Cancer Institute, Bethesda"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christine","family":"Mya-San","sequence":"additional","affiliation":[{"name":"Immunocompromised Host Section, Pediatric Oncology Branch, National Cancer Institute, Bethesda"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Johanna E.","family":"Hughes","sequence":"additional","affiliation":[{"name":"Immunocompromised Host Section, Pediatric Oncology Branch, National Cancer Institute, Bethesda"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Margaret P.","family":"Cotton","sequence":"additional","affiliation":[{"name":"Immunocompromised Host Section, Pediatric Oncology Branch, National Cancer Institute, Bethesda"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John","family":"Bacher","sequence":"additional","affiliation":[{"name":"Surgery Service, Division of Veterinary Resources, Office of Research Services, Bethesda, Maryland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thomas J.","family":"Walsh","sequence":"additional","affiliation":[{"name":"Immunocompromised Host Section, Pediatric Oncology Branch, National Cancer Institute, Bethesda"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"235","reference":[{"key":"e_1_3_1_2_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10096-005-0025-7"},{"key":"e_1_3_1_3_2","doi-asserted-by":"publisher","DOI":"10.1128\/JCM.42.1.236-238.2004"},{"key":"e_1_3_1_4_2","doi-asserted-by":"publisher","DOI":"10.1542\/peds.112.3.634"},{"key":"e_1_3_1_5_2","doi-asserted-by":"crossref","first-page":"712","DOI":"10.1542\/peds.106.4.712","volume":"106","year":"2000","unstructured":"Benjamin, D. 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