{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T01:42:10Z","timestamp":1792114930772,"version":"4.4.0"},"reference-count":37,"publisher":"American Society for Microbiology","issue":"6","license":[{"start":{"date-parts":[[2010,6,1]],"date-time":"2010-06-01T00:00:00Z","timestamp":1275350400000},"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":[[2010,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            We analyzed 71 clinical and environmental\n            <jats:italic>Cryptococcus gattii<\/jats:italic>\n            strains that had been isolated before or after the advent of azole antifungals to determine their level of heteroresistance to fluconazole (LHF). All strains of\n            <jats:italic>C. gattii<\/jats:italic>\n            manifested heteroresistance, with LHFs that ranged between 4 \u03bcg\/ml and 32 \u03bcg\/ml. A considerably higher proportion of the\n            <jats:italic>C. gattii<\/jats:italic>\n            strains (86%) than\n            <jats:italic>Cryptococcus neoformans<\/jats:italic>\n            strains (46%) exhibited LHFs that were \u226516 \u03bcg\/ml. No significant correlation was observed between the molecular type or serotypes of strains and their respective LHF. The strains which expressed a higher LHF were also more resistant to xenobiotics than the strains with a low LHF, and the level of resistance to xenobiotics was significantly higher than that reported for\n            <jats:italic>C. neoformans<\/jats:italic>\n            . The heteroresistant subpopulation, whose level of drug resistance had been raised in a stepwise manner to 64 \u03bcg\/ml, reverted to the original LHF upon daily transfers in drug-free medium. Importantly, the strains with high LHFs were significantly more virulent than those with low LHFs. Since all the clinical isolates that had not been exposed to azole drugs as well as the environmental strains manifested heteroresistance to fluconazole, heteroresistance of\n            <jats:italic>C. gattii<\/jats:italic>\n            to azoles is an intrinsic mechanism as in\n            <jats:italic>C. neoformans<\/jats:italic>\n            and is associated with the strain's virulence.\n          <\/jats:p>","DOI":"10.1128\/aac.00153-10","type":"journal-article","created":{"date-parts":[[2010,4,13]],"date-time":"2010-04-13T03:45:08Z","timestamp":1271130308000},"page":"2303-2311","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":92,"title":["Heteroresistance of\n            <i>Cryptococcus gattii<\/i>\n            to Fluconazole"],"prefix":"10.1128","volume":"54","author":[{"given":"A.","family":"Varma","sequence":"first","affiliation":[{"name":"Molecular Microbiology Section, Laboratory of Clinical Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K. J.","family":"Kwon-Chung","sequence":"additional","affiliation":[{"name":"Molecular Microbiology Section, Laboratory of Clinical Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","first-page":"1337","volume":"23","year":"1996","unstructured":"Armengou, A., C. Porcar, J. Mascaro, and F. Garcia-Bragado. 1996. Possible development of resistance to fluconazole during suppressive therapy for AIDS-associated cryptococcal meningitis. Clin. Infect. Dis.23:1337-1338.","journal-title":"Clin. Infect. Dis."},{"key":"e_1_3_2_3_2","first-page":"186","volume":"26","year":"1998","unstructured":"Berg, J., C. J. Clancy, and M. H. Nguyen. 1998. The hidden danger of primary fluconazole prophylaxis for patients with AIDS. Clin. Infect. Dis.26:186-187.","journal-title":"Clin. Infect. 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