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There are estimated to be almost 1 million cases per year of cryptococcal meningitis in patients infected with human immunodeficiency virus, leading to over 600,000 annual deaths, with a particular burden in sub-Saharan Africa. Amphotericin B (AMB) and fluconazole (FLC) are key components of cryptococcal meningitis treatment: AMB is used for induction, and FLC is for consolidation, maintenance and, for occasional individuals, prophylaxis. However, the results of standard antifungal susceptibility testing (AFST) for AMB and FLC do not correlate well with therapeutic outcomes and, consequently, no clinical breakpoints have been established. While a number of explanations for this absence of correlation have been proffered, one potential reason that has not been adequately explored is the possibility that the physiological differences between the\n            <jats:italic>in vivo<\/jats:italic>\n            infection environment and the\n            <jats:italic>in vitro<\/jats:italic>\n            AFST environment lead to disparate drug susceptibilities. These susceptibility-influencing factors include melanization, which does not occur during AFST, the size of the polysaccharide capsule, which is larger in infecting cells than in those grown under normal laboratory conditions, and the presence of large polyploid \u201ctitan cells,\u201d which rarely occur under laboratory conditions. Understanding whether and how\n            <jats:named-content content-type=\"genus-species\">C. neoformans<\/jats:named-content>\n            differentially expresses mechanisms of resistance to AMB and FLC in the AFST environment compared to the\n            <jats:italic>in vivo<\/jats:italic>\n            environment could enhance our ability to interpret AFST results and possibly lead to the development of more applicable testing methods.\n          <\/jats:p>","DOI":"10.1128\/aac.02108-16","type":"journal-article","created":{"date-parts":[[2016,12,29]],"date-time":"2016-12-29T02:30:21Z","timestamp":1482978621000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":29,"title":["Physiological Differences in Cryptococcus neoformans Strains\n            <i>In Vitro<\/i>\n            versus\n            <i>In Vivo<\/i>\n            and Their Effects on Antifungal Susceptibility"],"prefix":"10.1128","volume":"61","author":[{"given":"Nina T.","family":"Grossman","sequence":"first","affiliation":[{"name":"Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9402-9167","authenticated-orcid":false,"given":"Arturo","family":"Casadevall","sequence":"additional","affiliation":[{"name":"Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"235","reference":[{"key":"e_1_3_1_2_2","doi-asserted-by":"publisher","DOI":"10.1097\/QAD.0b013e328322ffac"},{"key":"e_1_3_1_3_2","doi-asserted-by":"publisher","DOI":"10.1086\/649858"},{"key":"e_1_3_1_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(05)70197-3"},{"key":"e_1_3_1_5_2","doi-asserted-by":"publisher","DOI":"10.1128\/JCM.00937-12"},{"key":"e_1_3_1_6_2","volume-title":"Reference method for broth dilution antifungal susceptibility testing of yeasts; approved standard","author":"Clinical and Laboratory Standards Institute","year":"2008","unstructured":"Clinical and Laboratory Standards Institute. 2008. 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