{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,21]],"date-time":"2026-03-21T20:02:01Z","timestamp":1774123321275,"version":"3.50.1"},"reference-count":25,"publisher":"American Society for Microbiology","issue":"2","license":[{"start":{"date-parts":[[1999,2,1]],"date-time":"1999-02-01T00:00:00Z","timestamp":917827200000},"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":[[1999,2]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>A murine model of intratracheally induced histoplasmosis was used to evaluate a new triazole antifungal agent, Schering (SCH) 56592, for treatment of histoplasmosis. MICs were determined for SCH 56592, amphotericin B, and itraconazole by testing yeast-phase isolates from 20 patients by a macrobroth dilution method. The MICs at which 90% of the isolates are inhibited were for 0.019 \u03bcg\/ml for SCH 56592, 0.5 \u03bcg\/ml for amphotericin B, and \u22640.019 \u03bcg\/ml for itraconazole. Survival studies were done on groups of 10 B6C3F<jats:sub>1<\/jats:sub>mice with a lethal inoculum of 10<jats:sup>5<\/jats:sup>. All mice receiving 5, 1, or 0.25 mg of SCH 56592 per kg of body weight per day, 2.5 mg of amphotericin B per kg every other day (qod), or 75 mg of itraconazole per kg per day survived to day 29. Only 44% of mice receiving 5 mg of itraconazole\/kg\/day survived to day 29. Fungal burden studies done in similar groups of mice with a sublethal inoculum of 10<jats:sup>4<\/jats:sup>showed a reduction in CFUs and<jats:italic>Histoplasma<\/jats:italic>antigen levels in lung and spleen tissue in animals treated with 2 mg of amphotericin B\/kg qod, 1 mg of SCH 56592\/kg\/day, and 75 mg of itraconazole\/kg\/day, but not in those treated with lower doses of the study drugs (0.2 mg of amphotericin B\/kg qod, 0.1 mg of SCH 56592\/kg\/day, or 10 mg of itraconazole\/kg\/day). Serum drug concentrations were measured 3 and 24 h after the last dose in mice (groups of five to seven mice), each treated for 7 days with SCH 56592 (10 and 1 mg\/kg\/day) and itraconazole (75 and 10 mg\/kg\/day). Mean levels measured by bioassay were as follows: SCH 56592, 10 mg\/kg\/day (2.15 \u03bcg\/ml at 3 h and 0.35 \u03bcg\/ml at 24 h); SCH 56592, 1 mg\/kg\/day (0.54 \u03bcg\/ml at 3 h and none detected at 24 h); itraconazole, 75 mg\/kg\/day (22.53 \u03bcg\/ml at 3 h and none detected at 24 h); itraconazole, 10 mg\/kg\/day (1.33 \u03bcg\/ml at 3 h and none detected at 24 h). Confirmatory results were obtained by high-pressure liquid chromatography assay. These studies show SCH 56592 to be a promising candidate for studies of treatment of histoplasmosis in humans.<\/jats:p>","DOI":"10.1128\/aac.43.2.322","type":"journal-article","created":{"date-parts":[[2018,10,9]],"date-time":"2018-10-09T00:34:13Z","timestamp":1539045253000},"page":"322-328","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":62,"title":["Comparison of a New Triazole Antifungal Agent, Schering 56592, with Itraconazole and Amphotericin B for Treatment of Histoplasmosis in Immunocompetent Mice"],"prefix":"10.1128","volume":"43","author":[{"given":"Patricia","family":"Connolly","sequence":"first","affiliation":[{"name":"<!--label omitted: 1-->Department of Medicine1 and"},{"name":"<!--label omitted: 2-->Histoplasmosis Reference Laboratory,2 Indianapolis, Indiana, and"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joe","family":"Wheat","sequence":"additional","affiliation":[{"name":"<!--label omitted: 1-->Department of Medicine1 and"},{"name":"<!--label omitted: 3-->Department of Pathology and Laboratory Medicine,3 Indiana University School of Medicine,"},{"name":"<!--label omitted: 4-->Department of Veterans\u2019 Affairs Hospital,4 and"},{"name":"<!--label omitted: 2-->Histoplasmosis Reference Laboratory,2 Indianapolis, Indiana, and"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carol","family":"Schnizlein-Bick","sequence":"additional","affiliation":[{"name":"<!--label omitted: 1-->Department of Medicine1 and"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michelle","family":"Durkin","sequence":"additional","affiliation":[{"name":"<!--label omitted: 1-->Department of Medicine1 and"},{"name":"<!--label omitted: 2-->Histoplasmosis Reference Laboratory,2 Indianapolis, Indiana, and"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Steve","family":"Kohler","sequence":"additional","affiliation":[{"name":"<!--label omitted: 4-->Department of Veterans\u2019 Affairs Hospital,4 and"},{"name":"<!--label omitted: 2-->Histoplasmosis Reference Laboratory,2 Indianapolis, Indiana, and"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Melinda","family":"Smedema","sequence":"additional","affiliation":[{"name":"<!--label omitted: 1-->Department of Medicine1 and"},{"name":"<!--label omitted: 2-->Histoplasmosis Reference Laboratory,2 Indianapolis, Indiana, and"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Janet","family":"Goldberg","sequence":"additional","affiliation":[{"name":"<!--label omitted: 1-->Department of Medicine1 and"},{"name":"<!--label omitted: 2-->Histoplasmosis Reference Laboratory,2 Indianapolis, Indiana, and"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Edward","family":"Brizendine","sequence":"additional","affiliation":[{"name":"<!--label omitted: 1-->Department of Medicine1 and"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David","family":"Loebenberg","sequence":"additional","affiliation":[{"name":"<!--label omitted: 5-->Schering-Plough Research Institute, Kenilworth, New Jersey5"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1128\/jcm.22.2.157-160.1985"},{"key":"e_1_3_2_3_2","unstructured":"Cacciapuoti A. 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