{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,19]],"date-time":"2026-03-19T12:29:52Z","timestamp":1773923392811,"version":"3.50.1"},"reference-count":31,"publisher":"American Society for Microbiology","issue":"2","license":[{"start":{"date-parts":[[2010,2,1]],"date-time":"2010-02-01T00:00:00Z","timestamp":1264982400000},"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":[[2010,2]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            The\n            <jats:italic>in vivo<\/jats:italic>\n            efficacy of posaconazole against 4 clinical\n            <jats:italic>Aspergillus fumigatus<\/jats:italic>\n            isolates with posaconazole MICs ranging from 0.03 to 16 mg\/liter, as determined by CLSI method M38A, was assessed in a nonneutropenic murine model of disseminated aspergillosis. The underlying resistance mechanisms of the isolates included substitutions in the\n            <jats:italic>cyp51A<\/jats:italic>\n            gene at codon 220 (M220I), codon 54 (G54W), and codon 98 (L98H). The latter was combined with a 34-bp tandem repeat in the gene promoter region (TR L98H). The control isolate exhibited a wild-type phenotype without any known resistance mechanism. Oral posaconazole therapy was started 24 h after infection and was given once daily for 14 consecutive days. Mice were treated with four different doses (1 to 64 mg\/kg of body weight), and survival was used as the end point. Survival was dependent both on the dose and on the MIC. The Hill equation with a variable slope fitted the relationship between the dose\/MIC ratio and 14-day survival well (\n            <jats:italic>R<\/jats:italic>\n            <jats:sup>2<\/jats:sup>\n            , 0.92), with a 50% effective dose (ED\n            <jats:sub>50<\/jats:sub>\n            ) of 29.0 mg\/kg (95% confidence interval [CI], 15.6 to 53.6 mg\/kg). This also applied to the relationship between the area under the plasma concentration-time curve (AUC)\/MIC ratio and 14-day survival (50% effective pharmacodynamic index [EI\n            <jats:sub>50<\/jats:sub>\n            ], 321.3 [95% CI, 222.7 to 463.4]). Near-maximum survival was reached at an AUC\/MIC ratio of nearly 1,000. These results indicate that treatment of infections with\n            <jats:italic>A. fumigatus<\/jats:italic>\n            strains for which MICs are 0.5 mg\/liter requires doses exceeding the present licensed doses. Increasing the standard dosing regimen may have some effect and may be clinically useful if no alternatives are available.\n          <\/jats:p>","DOI":"10.1128\/aac.00931-09","type":"journal-article","created":{"date-parts":[[2009,11,17]],"date-time":"2009-11-17T02:57:00Z","timestamp":1258426620000},"page":"860-865","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":103,"title":["Efficacy of Posaconazole against Three Clinical\n            <i>Aspergillus fumigatus<\/i>\n            Isolates with Mutations in the\n            <i>cyp51A<\/i>\n            Gene"],"prefix":"10.1128","volume":"54","author":[{"given":"Eleftheria","family":"Mavridou","sequence":"first","affiliation":[{"name":"Departments of Medical Microbiology"},{"name":"Nijmegen Institute for Infection, Inflammation and Immunity"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Roger J. M.","family":"Bru\u0308ggemann","sequence":"additional","affiliation":[{"name":"Clinical Pharmacy, Radboud University Nijmegen Medical Centre"},{"name":"Nijmegen Institute for Infection, Inflammation and Immunity"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Willem J. G.","family":"Melchers","sequence":"additional","affiliation":[{"name":"Departments of Medical Microbiology"},{"name":"Nijmegen Institute for Infection, Inflammation and Immunity"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Johan W.","family":"Mouton","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology and Infectious Diseases, Canisius Wilhelmina Hospital, Nijmegen, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paul E.","family":"Verweij","sequence":"additional","affiliation":[{"name":"Departments of Medical Microbiology"},{"name":"Nijmegen Institute for Infection, Inflammation and Immunity"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.48.1.137-142.2004"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1093\/clinids\/17.Supplement_2.S481"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00190-08"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/167.5.1247"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00901-08"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkh507"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.47.9.2788-2795.2003"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/47.3.333"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1099\/jmm.0.46639-0"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.41.6.1364"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1124\/dmd.32.2.267"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1080\/13693780802545600"},{"key":"e_1_3_2_14_2","unstructured":"Emerg. 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