{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,21]],"date-time":"2026-03-21T20:01:59Z","timestamp":1774123319935,"version":"3.50.1"},"reference-count":22,"publisher":"American Society for Microbiology","issue":"3","license":[{"start":{"date-parts":[[1998,3,1]],"date-time":"1998-03-01T00:00:00Z","timestamp":888710400000},"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":[[1998,3]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            Studies with animals and in vitro studies have demonstrated that flucytosine plus amphotericin B or fluconazole has significantly improved mycologic activity against meningitis caused by\n            <jats:italic>Cryptococcus neoformans<\/jats:italic>\n            compared to the activity of amphotericin B or fluconazole used alone. However, few doses have been tested in combination. This study evaluated the antifungal efficacy of amphotericin B colloidal dispersion (ABCD) combined with flucytosine with and without fluconazole in a murine model of cryptococcal meningitis. The following dosages were tested: ABCD at 0 to 12.5 mg\/kg of body weight given intravenously 3 days\/week, flucytosine at 0 to 110 mg\/kg\/day, and fluconazole at 0 to 50 mg\/kg\/day. Meningitis was established in male BALB\/c mice by intracerebral injection of\n            <jats:italic>C. neoformans<\/jats:italic>\n            . Treatment with flucytosine with or without fluconazole dissolved in the sole source of drinking water was started on day 2; animals were sacrificed at 16 days, and the numbers of fungal colonies in the brain were quantified. A survival rate of 100% was achieved with ABCD plus flucytosine without fluconazole; however, the addition of fluconazole was required to prevent weight loss (\n            <jats:italic>P<\/jats:italic>\n            &lt; 0.00001) and to achieve the maximum antifungal effect (\n            <jats:italic>P<\/jats:italic>\n            &lt; 0.00001). The only region of dose combinations for which the 99% confidence intervals were less than 100 CFU\/g of brain was defined by ABCD at 5.0 to 7.5 mg\/kg combined with flucytosine at 20 to 60 mg\/kg\/day and fluconazole at 30 to 40 mg\/kg\/day. The triple combination of ABCD plus flucytosine and fluconazole was necessary to achieve the greatest antifungal activity.\n          <\/jats:p>","DOI":"10.1128\/aac.42.3.528","type":"journal-article","created":{"date-parts":[[2018,10,9]],"date-time":"2018-10-09T00:30:35Z","timestamp":1539045035000},"page":"528-533","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":50,"title":["Amphotericin B Colloidal Dispersion Combined with Flucytosine with or without Fluconazole for Treatment of Murine Cryptococcal Meningitis"],"prefix":"10.1128","volume":"42","author":[{"given":"DeAnn M.","family":"Diamond","sequence":"first","affiliation":[{"name":"<!--label omitted: 1-->Departments of Medicine (Infectious Diseases)1 and"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Madeline","family":"Bauer","sequence":"additional","affiliation":[{"name":"<!--label omitted: 2-->Preventive Medicine (Biostatistics),2 University of Southern California, Los Angeles, California;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Barbra E.","family":"Daniel","sequence":"additional","affiliation":[{"name":"<!--label omitted: 3-->Preclinical Research Department, SEQUUS Pharmaceuticals, Inc., Menlo Park, California3;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mary Ann E.","family":"Leal","sequence":"additional","affiliation":[{"name":"<!--label omitted: 1-->Departments of Medicine (Infectious Diseases)1 and"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Debra","family":"Johnson","sequence":"additional","affiliation":[{"name":"<!--label omitted: 1-->Departments of Medicine (Infectious Diseases)1 and"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Byron K.","family":"Williams","sequence":"additional","affiliation":[{"name":"<!--label omitted: 1-->Departments of Medicine (Infectious Diseases)1 and"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ann M.","family":"Thomas","sequence":"additional","affiliation":[{"name":"<!--label omitted: 4-->Department of Statistics, University of Northern Colorado, Greeley, Colorado4; and"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"James C.","family":"Ding","sequence":"additional","affiliation":[{"name":"<!--label omitted: 1-->Departments of Medicine (Infectious Diseases)1 and"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Laura","family":"Najvar","sequence":"additional","affiliation":[{"name":"<!--label omitted: 5-->Division of Infectious Diseases, University of Texas Health Sciences Center, San Antonio, Texas5"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J. Richard","family":"Graybill","sequence":"additional","affiliation":[{"name":"<!--label omitted: 5-->Division of Infectious Diseases, University of Texas Health Sciences Center, San Antonio, Texas5"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robert A.","family":"Larsen","sequence":"additional","affiliation":[{"name":"<!--label omitted: 1-->Departments of Medicine (Infectious Diseases)1 and"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.35.4.726"},{"issue":"4","key":"e_1_3_2_3_2","first-page":"10","article-title":"Loess regression in evaluation of dose response surfaces.","volume":"13","author":"Bauer M.","year":"1996","unstructured":"Bauer M. Thomas A. M. Loess regression in evaluation of dose response surfaces. Biom. Bull. 13 4 1996 10","journal-title":"Biom. 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W.\n          Understanding robust and exploratory data analysis.\n          1983\n          John Wiley & Sons Inc.\n          New York N.Y"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1080\/01621459.1958.10501452"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.40.9.2178"},{"key":"e_1_3_2_14_2","doi-asserted-by":"crossref","first-page":"741","DOI":"10.1093\/clinids\/19.4.741","article-title":"Fluconazole combined with flucytosine for the treatment of cryptococcal meningitis in patients with AIDS.","volume":"19","author":"Larsen R. A.","year":"1994","unstructured":"Larsen R. A. Bozzette S. A. Jones B. E. Haghighat D. Leal M. A. Forthal D. Bauer M. Tilles J. G. McCutchan J. A. Leedom J. M. Fluconazole combined with flucytosine for the treatment of cryptococcal meningitis in patients with AIDS. Clin. Infect. Dis. 19 1994 741 745","journal-title":"Clin. Infect. 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Espinel-Ingroff A. Davis B. In vitro studies with combinations of 5-fluorocytosine and amphotericin B. Antimicrob. Agents Chemother. 28 1975 117 121","journal-title":"Antimicrob. Agents Chemother."},{"key":"e_1_3_2_22_2","unstructured":"Statistical Sciences Inc\n          S- plus guide to statistical and mathematical analysis version 3.3 for Windows.\n          1995\n          MathSoft Inc.\n          Seattle Wash"},{"key":"e_1_3_2_23_2","doi-asserted-by":"crossref","unstructured":"Venables\n              W. N.\n              Ripley\n              B. 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