{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T11:33:57Z","timestamp":1790508837577,"version":"4.1.0"},"reference-count":29,"publisher":"American Society for Microbiology","issue":"5","license":[{"start":{"date-parts":[[2001,5,1]],"date-time":"2001-05-01T00:00:00Z","timestamp":988675200000},"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":[[2001,5]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>A checkerboard methodology, based on standardized methods proposed by the National Committee for Clinical Laboratory Standards for broth microdilution antifungal susceptibility testing, was applied to study the in vitro interactions of flucytosine (FC) and posaconazole (SCH 56592) (FC-SCH) against 15 isolates of<jats:italic>Cryptococcus neoformans<\/jats:italic>. Synergy, defined as a fractional inhibitory concentration (FIC) index of &lt;0.50, was observed for 33% of the isolates tested. When synergy was not achieved, there was still a decrease in the MIC of one or both drugs when they were used in combination. Antagonism, defined as a FIC of &gt;4.0, was not observed. The in vitro efficacy of combined therapy was confirmed by quantitative determination of the CFU of<jats:italic>C. neoformans<\/jats:italic>486, an isolate against which the FC-SCH association yielded a synergistic interaction. To investigate the potential beneficial effects of this combination therapy in vivo, we established two experimental murine models of cryptococcosis by intracranial or intravenous injection of cells of<jats:italic>C. neoformans<\/jats:italic>486. At 1 day postinfection, the mice were randomized into different treatment groups. One group each received each drug alone, and one group received the drugs in combination. While combination therapy was not found to be significantly more effective than each single drug in terms of survival, tissue burden experiments confirmed the potentiation of antifungal activity with the combination. Our study demonstrates that SCH and FC combined are significantly more active than either drug alone against<jats:italic>C. neoformans<\/jats:italic>in vitro as well in vivo. These findings suggest that this therapeutic approach could be useful in the treatment of cryptococcal infections.<\/jats:p>","DOI":"10.1128\/aac.45.5.1355-1359.2001","type":"journal-article","created":{"date-parts":[[2002,7,27]],"date-time":"2002-07-27T10:06:42Z","timestamp":1027764402000},"page":"1355-1359","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":35,"title":["Interactions of Posaconazole and Flucytosine against<i>Cryptococcus neoformans<\/i>"],"prefix":"10.1128","volume":"45","author":[{"given":"Francesco","family":"Barchiesi","sequence":"first","affiliation":[{"name":"<!--label omitted: 1-->Istituto di Malattie Infettive e Medicina Pubblica1 and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna Maria","family":"Schimizzi","sequence":"additional","affiliation":[{"name":"<!--label omitted: 1-->Istituto di Malattie Infettive e Medicina Pubblica1 and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura K.","family":"Najvar","sequence":"additional","affiliation":[{"name":"<!--label omitted: 2-->University of Texas Health Science Center at San Antonio and Audie Murphy Veterans Administration Hospital, San Antonio, Texas2"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rosie","family":"Bocanegra","sequence":"additional","affiliation":[{"name":"<!--label omitted: 2-->University of Texas Health Science Center at San Antonio and Audie Murphy Veterans Administration Hospital, San Antonio, Texas2"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca","family":"Caselli","sequence":"additional","affiliation":[{"name":"<!--label omitted: 1-->Istituto di Malattie Infettive e Medicina Pubblica1 and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simona","family":"Di Cesare","sequence":"additional","affiliation":[{"name":"<!--label omitted: 1-->Istituto di Malattie Infettive e Medicina Pubblica1 and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniele","family":"Giannini","sequence":"additional","affiliation":[{"name":"<!--label omitted: 1-->Istituto di Malattie Infettive e Medicina Pubblica1 and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luigi Falconi","family":"Di Francesco","sequence":"additional","affiliation":[{"name":"<!--label omitted: 1-->Istituto di Malattie Infettive e Medicina Pubblica1 and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Giacometti","sequence":"additional","affiliation":[{"name":"<!--label omitted: 1-->Istituto di Malattie Infettive e Medicina Pubblica1 and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Flavia","family":"Carle","sequence":"additional","affiliation":[{"name":"<!--label omitted: 3-->Centro Interdipartimentale di Epidemiologia, Biostatistica e Informatica Medica,3 Universita\u0300 degli Studi di Ancona, Ancona, Italy; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giorgio","family":"Scalise","sequence":"additional","affiliation":[{"name":"<!--label omitted: 1-->Istituto di Malattie Infettive e Medicina Pubblica1 and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John R.","family":"Graybill","sequence":"additional","affiliation":[{"name":"<!--label omitted: 2-->University of Texas Health Science Center at San Antonio and Audie Murphy Veterans Administration Hospital, San Antonio, Texas2"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.35.9.1721"},{"key":"e_1_3_2_3_2","first-page":"xvii","article-title":"Instructions to authors.","volume":"45","author":"American Society for Microbiology","year":"2001","unstructured":"American Society for Microbiology Instructions to authors. 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