{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T14:46:53Z","timestamp":1792075613129,"version":"4.4.0"},"reference-count":31,"publisher":"Oxford University Press (OUP)","issue":"10","license":[{"start":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T00:00:00Z","timestamp":1789948800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/501100004916","name":"FAPEAM","doi-asserted-by":"publisher","award":["001-2023"],"award-info":[{"award-number":["001-2023"]}],"id":[{"id":"10.13039\/501100004916","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003593","name":"National Council for Scientific and Technological Development","doi-asserted-by":"publisher","award":["10-2023"],"award-info":[{"award-number":["10-2023"]}],"id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,10,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Cryptococcosis is a severe systemic mycosis, and relapse may be influenced by fungal subpopulations that survive fluconazole exposure. This retrospective cohort study investigated whether fluconazole minimum inhibitory concentration (MIC) and the heteroresistant (HetR) phenotype of the first available diagnostic cerebrospinal-fluid isolate were associated with recorded relapse within 6 months in 70 patients with neurocryptococcosis from Amazonas, Brazil. One clinical isolate per patient, comprising 64 Cryptococcus neoformans molecular type\u00a0VNI and 6 Cryptococcus gattii molecular type VGII isolates, was evaluated by broth microdilution and endpoint-based fluconazole heteroresistance level (HFL) testing. Using an operational criterion of HFL\/MIC \u2265 8, corresponding to visible growth at least three twofold dilutions above the MIC, 43 of 70 isolates (61.4%) were classified as displaying a HetR phenotype. Six-month follow-up was available for 69 patients. Recorded relapse occurred in 12 of 42 patients infected with HetR isolates (28.6%) and in 4 of 27 patients infected with non-HetR isolates (14.8%). Although relapse was numerically more frequent in the HetR group, the association was not statistically significant (conditional odds ratio, 2.27; exact 95% confidence interval, 0.59\u201310.96; two-sided Fisher\u2019s exact test, P = .248). The\u00a0HFL\/MIC ratio also did not differ significantly according to recorded relapse status (P = .165). The HetR phenotype of the first available diagnostic isolate, defined operationally in this study as HFL\/MIC \u2265 8, was frequent but was not significantly associated with recorded relapse within 6 months in this cohort.<\/jats:p>","DOI":"10.1093\/mmy\/myag102","type":"journal-article","created":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T18:28:24Z","timestamp":1789756104000},"source":"Crossref","is-referenced-by-count":0,"title":["Baseline fluconazole heteroresistance and risk of relapse within 6 months among patients with neurocryptococcosis in the Brazilian Amazon"],"prefix":"10.1093","volume":"64","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7032-8082","authenticated-orcid":false,"given":"Izabela de Mesquita B\u00e1rcia","family":"Moreira","sequence":"first","affiliation":[{"name":"Postgraduate Program in Biodiversity and Biotechnology, BIONORTE Network , Manaus,69065-001 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Oliveira","family":"de\u00a0Sousa","sequence":"additional","affiliation":[{"name":"Mycology Laboratory, National Institute for Amazonian Research (INPA) , Manaus, 69067-375 ,","place":["Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9630-0029","authenticated-orcid":false,"given":"Juan Diego Ribeiro","family":"de\u00a0Almeida","sequence":"additional","affiliation":[{"name":"Multicenter Graduate Program in Biochemistry and Molecular Biology, State University of Amazonas (UEA) , Manaus, 69065-001 ,","place":["Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-9176-4271","authenticated-orcid":false,"given":"Robert Langlady Lira Rosas","family":"Filho","sequence":"additional","affiliation":[{"name":"Postgraduate Program in Pharmaceutical Sciences, Federal University of Amazonas (UFAM) , Manaus, 69080-900 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Silva","family":"Santos","sequence":"additional","affiliation":[{"name":"Postgraduate Program in Biotechnology and Biosciences Applied to Pharmacy, S\u00e3o Paulo State University (UNESP) , Araraquara,14800-903 ,","place":["Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5686-1828","authenticated-orcid":false,"given":"Ani Beatriz Jackisch","family":"Matsuura","sequence":"additional","affiliation":[{"name":"Le\u00f4nidas & Maria Deane Research Center, Oswaldo Cruz Foundation (FIOCRUZ) , Manaus, 69057-070 ,","place":["Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2389-4401","authenticated-orcid":false,"given":"\u00c9rica Simpl\u00edcio","family":"de\u00a0Souza","sequence":"additional","affiliation":[{"name":"Higher School of Technology, State University of Amazonas (UEA) , Manaus, 69050-020 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