{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,15]],"date-time":"2026-04-15T13:08:26Z","timestamp":1776258506411,"version":"3.50.1"},"reference-count":30,"publisher":"American Society for Microbiology","issue":"2","license":[{"start":{"date-parts":[[2013,2,1]],"date-time":"2013-02-01T00:00:00Z","timestamp":1359676800000},"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":[[2013,2]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            Miltefosine is an alkyl phosphocholine with good oral bioavailability and\n            <jats:italic>in vitro<\/jats:italic>\n            activity against\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Cryptococcus<\/jats:named-content>\n            species that has gained interest as an additional agent for cryptococcal infections. Our objective was to further evaluate the\n            <jats:italic>in vivo<\/jats:italic>\n            efficacy of miltefosine in experimental\n            <jats:italic>in vivo<\/jats:italic>\n            models of cryptococcal meningoencephalitis and disseminated cryptococcosis. Mice were infected intracranially or intravenously with either\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">C. neoformans<\/jats:named-content>\n            USC1597 or H99. Miltefosine treatment (1.8 to 45 mg\/kg of body weight orally once daily) began at either 1 h or 1 day postinoculation. Fluconazole (10 mg\/kg orally twice daily) or amphotericin B deoxycholate (3 mg\/kg intraperitoneally once daily) served as positive controls. In our standard models, miltefosine did not result in significant improvements in survival or reductions in fungal burden against either\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">C. neoformans<\/jats:named-content>\n            isolate. There was a trend toward improved survival with miltefosine at 7.2 mg\/kg against disseminated cryptococcosis with the H99 strain but only at a low infecting inoculum. In contrast, both fluconazole and amphotericin B significantly improved survival in mice with cryptococcal meningoencephalitis and disseminated cryptococcosis due to USC1597. Amphotericin B also improved survival against both cryptococcal infections caused by H99. Combination therapy with miltefosine demonstrated neither synergy nor antagonism in both models. These results demonstrate limited efficacy of miltefosine and suggest caution with the potential use of this agent for the treatment of\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">C. neoformans<\/jats:named-content>\n            infections.\n          <\/jats:p>","DOI":"10.1128\/aac.01624-12","type":"journal-article","created":{"date-parts":[[2012,11,20]],"date-time":"2012-11-20T05:25:19Z","timestamp":1353389119000},"page":"745-750","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":35,"title":["Limited Activity of Miltefosine in Murine Models of Cryptococcal Meningoencephalitis and Disseminated Cryptococcosis"],"prefix":"10.1128","volume":"57","author":[{"given":"Nathan P.","family":"Wiederhold","sequence":"first","affiliation":[{"name":"University of Texas Health Science Center at San Antonio, San Antonio, Texas, USA"},{"name":"University of Texas at Austin College of Pharmacy, Austin, Texas, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Laura K.","family":"Najvar","sequence":"additional","affiliation":[{"name":"University of Texas Health Science Center at San Antonio, San Antonio, Texas, USA"},{"name":"South Texas Veterans Health Care Administration, San Antonio, Texas, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rosie","family":"Bocanegra","sequence":"additional","affiliation":[{"name":"University of Texas Health Science Center at San Antonio, San Antonio, Texas, USA"},{"name":"South Texas Veterans Health Care Administration, San Antonio, Texas, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"William R.","family":"Kirkpatrick","sequence":"additional","affiliation":[{"name":"University of Texas Health Science Center at San Antonio, San Antonio, Texas, USA"},{"name":"South Texas Veterans Health Care Administration, San Antonio, Texas, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tania C.","family":"Sorrell","sequence":"additional","affiliation":[{"name":"Sydney Emerging Infections and Biosecurity Institute, Sydney, Australia"},{"name":"University of Sydney, Sydney, Australia"},{"name":"Westmead Millennium Institute, Sydney, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thomas F.","family":"Patterson","sequence":"additional","affiliation":[{"name":"University of Texas Health Science Center at San Antonio, San Antonio, Texas, USA"},{"name":"South Texas Veterans Health Care Administration, San Antonio, Texas, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.idc.2006.07.001"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1086\/649858"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1097\/QAD.0b013e328322ffac"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pmed.0040021"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1097\/01.aids.0000252060.80704.68"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.7326\/0003-4819-113-3-183"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199201093260202"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1086\/380638"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1086\/519690"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199912093412403"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1086\/383321"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1086\/322689"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1086\/510588"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa021556"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(98)04367-0"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.trstmh.2006.02.010"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01382-06"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.50.2.414-421.2006"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1086\/597772"},{"key":"e_1_3_2_21_2","volume-title":"Approved standard M27-A3","author":"CLSI","year":"2008","unstructured":"CLSI. 2008. Reference method for broth dilution antifungal susceptibility testing of yeasts. Approved standard M27-A3, 3rd ed. Clinical and Laboratory Standards Institute, Wayne, PA.","edition":"3"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.42.3.528"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.41.7.1589"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dks060"},{"key":"e_1_3_2_25_2","volume-title":"Guide for the care and use of laboratory animals.","author":"NAS","year":"1996","unstructured":"NAS. 1996. Guide for the care and use of laboratory animals. 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