{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,7]],"date-time":"2026-02-07T21:42:37Z","timestamp":1770500557732,"version":"3.49.0"},"reference-count":16,"publisher":"American Society for Microbiology","issue":"6","license":[{"start":{"date-parts":[[2000,6,1]],"date-time":"2000-06-01T00:00:00Z","timestamp":959817600000},"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":[[2000,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>Nikkomycin Z was tested both in vitro and in vivo for efficacy against<jats:italic>Histoplasma capsulatum<\/jats:italic>. Twenty clinical isolates were tested for susceptibility to nikkomycin Z in comparison to amphotericin B and itraconazole. The median MIC was 8 \u03bcg\/ml with a range of 4 to 64 \u03bcg\/ml for nikkomycin Z, 0.56 \u03bcg\/ml with a range of 0.5 to 1.0 \u03bcg\/ml for amphotericin B, and \u22640.019 \u03bcg\/ml for itraconazole. Primary studies were carried out by using a clinical isolate of<jats:italic>H. capsulatum<\/jats:italic>for which the MIC of nikkomycin Z was greater than or equal to 64 \u03bcg\/ml. In survival experiments, mice treated with amphotericin B at 2.0 mg\/kg\/dose every other day (QOD) itraconazole at 75 mg\/kg\/dose twice daily (BID), and nikkomycin Z at 100 mg\/kg\/dose BID survived to day 14, while 70% of mice receiving nikkomycin Z at 20 mg\/kg\/dose BID and none of the mice receiving nikkomycin Z at 5 mg\/kg\/dose BID survived to day 14. All vehicle control mice died by day 12. Fungal burden was assessed on survivors. Mice treated with nikkomycin Z at 20 and 100 mg\/kg\/dose BID had significantly higher CFUs per gram of organ weight in quantitative cultures and higher levels of<jats:italic>Histoplasma<\/jats:italic>antigen in lung and spleen homogenates than mice treated with amphotericin B at 2.0 mg\/kg\/dose QOD or itraconazole at 75 mg\/kg\/dose BID. Studies also were carried out with a clinical isolate for which the MIC of nikkomycin Z was 4 \u03bcg\/ml. All mice treated with amphotericin B at 2.0 mg\/kg\/dose QOD; itraconazole at 75 mg\/kg\/dose BID; and nikkomycin Z at 100, 20, and 5 mg\/kg\/dose BID survived until the end of the study at day 17 postinfection, while 30% of the untreated vehicle control mice survived. Fungal burden assessed on survivors showed similar levels of<jats:italic>Histoplasma<\/jats:italic>antigen in lung and spleen homogenates of mice treated with amphotericin B at 2.0 mg\/kg\/dose QOD; itraconazole at 75 mg\/kg\/dose BID; and nikkomycin Z at 100, 20, and 5 mg\/kg\/dose BID. The three surviving vehicle control mice had significantly higher antigen levels in lung and spleen than other groups (<jats:italic>P<\/jats:italic>&lt; 0.05). The efficacy of nikkomycin Z at preventing mortality and reducing fungal burden correlates with in vitro susceptibility.<\/jats:p>","DOI":"10.1128\/aac.44.6.1624-1629.2000","type":"journal-article","created":{"date-parts":[[2002,7,27]],"date-time":"2002-07-27T10:06:42Z","timestamp":1027764402000},"page":"1624-1629","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":32,"title":["Comparison of Nikkomycin Z with Amphotericin B and Itraconazole for Treatment of Histoplasmosis in a Murine Model"],"prefix":"10.1128","volume":"44","author":[{"given":"Janet","family":"Goldberg","sequence":"first","affiliation":[{"name":"<!--label omitted: 1-->Departments of Medicine1 and"},{"name":"<!--label omitted: 2-->Histoplasmosis Reference Laboratory,2 Indianapolis, Indiana, and"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Patricia","family":"Connolly","sequence":"additional","affiliation":[{"name":"<!--label omitted: 1-->Departments of Medicine1 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-->Departments of Medicine1 and"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michelle","family":"Durkin","sequence":"additional","affiliation":[{"name":"<!--label omitted: 1-->Departments of Medicine1 and"},{"name":"<!--label omitted: 2-->Histoplasmosis Reference Laboratory,2 Indianapolis, Indiana, and"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stephen","family":"Kohler","sequence":"additional","affiliation":[{"name":"<!--label omitted: 3-->Department of Veterans' Affairs Hospital,3 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-->Departments 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-->Departments of Medicine1 and"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Richard","family":"Hector","sequence":"additional","affiliation":[{"name":"<!--label omitted: 4-->Shaman Pharmaceuticals, South San Francisco, California4"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joseph","family":"Wheat","sequence":"additional","affiliation":[{"name":"<!--label omitted: 1-->Departments of Medicine1 and"},{"name":"<!--label omitted: 5-->Pathology,5 Indiana University School of Medicine,"},{"name":"<!--label omitted: 3-->Department of Veterans' Affairs Hospital,3 and"},{"name":"<!--label omitted: 2-->Histoplasmosis Reference Laboratory,2 Indianapolis, Indiana, and"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"235","reference":[{"key":"e_1_3_1_2_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.41.9.2026"},{"key":"e_1_3_1_3_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.43.2.322"},{"key":"e_1_3_1_4_2","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1080\/00031305.1981.10479327","article-title":"Rank transformations as a bridge between parametric and nonparametric statistics.","volume":"35","author":"Conover W. 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