{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T02:13:18Z","timestamp":1791511998785,"version":"4.3.4"},"reference-count":32,"publisher":"American Society for Microbiology","issue":"1","license":[{"start":{"date-parts":[[2012,1,1]],"date-time":"2012-01-01T00:00:00Z","timestamp":1325376000000},"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":[[2012,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            Secondary resistance to azoles in\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Aspergillus fumigatus<\/jats:named-content>\n            isolates from patients taking long-term itraconazole therapy has been described. We studied the acquisition of secondary azole resistance in 20\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">A. fumigatus<\/jats:named-content>\n            isolates with no mutations at codon 54, 98, 138, 220, 432, or 448 in the\n            <jats:italic>cyp51A<\/jats:italic>\n            gene. Adjusted conidium inocula (3 \u00d7 10\n            <jats:sup>7<\/jats:sup>\n            CFU\/ml) of each isolate were prepared and progressively or directly exposed to increasing itraconazole concentrations, ranging from 0.5 \u03bcg\/ml to 16 \u03bcg\/ml. Itraconazole, voriconazole, and posaconazole MICs were determined using the CLSI M38-A2 procedure before (MIC\n            <jats:sub>initial<\/jats:sub>\n            ) and after (MIC\n            <jats:sub>final<\/jats:sub>\n            ) exposure to itraconazole. In both procedures, the MIC\n            <jats:sub>final<\/jats:sub>\n            was significantly higher than the MIC\n            <jats:sub>initial<\/jats:sub>\n            . However, after progressive exposure to itraconazole, the MICs of the three azoles were higher than after direct exposure. No mutations were found at codon 54, 98, 138, 220, 432, or 448 in the\n            <jats:italic>cyp51A<\/jats:italic>\n            gene of isolates growing at the highest concentration of itraconazole. More concentrated conidium inocula (2 \u00d7 10\n            <jats:sup>9<\/jats:sup>\n            CFU\/ml) plated in itraconazole at 4 \u03bcg\/ml revealed the presence of heteroresistant populations in two initially wild-type isolates. These isolates became resistant to itraconazole and posaconazole only after use of the concentrated inoculum. These heteroresistant isolates harbored a mutation at codon G54, and the MICs of itraconazole and posaconazole were &gt;16 \u03bcg\/ml. In all procedures,\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">A. fumigatus<\/jats:named-content>\n            short tandem repeat (STR\n            <jats:italic>Af<\/jats:italic>\n            ) typing was used to demonstrate that the genotype did not change before or after exposure to itraconazole.\n          <\/jats:p>","DOI":"10.1128\/aac.00301-11","type":"journal-article","created":{"date-parts":[[2011,10,18]],"date-time":"2011-10-18T05:22:42Z","timestamp":1318915362000},"page":"174-178","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":48,"title":["<i>In Vitro<\/i>\n            Acquisition of Secondary Azole Resistance in Aspergillus fumigatus Isolates after Prolonged Exposure to Itraconazole: Presence of Heteroresistant Populations"],"prefix":"10.1128","volume":"56","author":[{"given":"Pilar","family":"Escribano","sequence":"first","affiliation":[{"name":"Clinical Microbiology and Infectious Diseases Department, Hospital General Universitario Gregorio Mara\u00f1\u00f3n, Universidad Complutense de Madrid, Madrid, Spain"},{"name":"Instituto de Investigaci\u00f3n Sanitaria del Hospital Gregorio Mara\u00f1\u00f3n, Madrid, Spain"},{"name":"CIBER de Enfermedades Respiratorias, Palma de Mallorca, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandra","family":"Recio","sequence":"additional","affiliation":[{"name":"Clinical Microbiology and Infectious Diseases Department, Hospital General Universitario Gregorio Mara\u00f1\u00f3n, Universidad Complutense de Madrid, Madrid, Spain"},{"name":"Instituto de Investigaci\u00f3n Sanitaria del Hospital Gregorio Mara\u00f1\u00f3n, Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Teresa","family":"Pel\u00e1ez","sequence":"additional","affiliation":[{"name":"Clinical Microbiology and Infectious Diseases Department, Hospital General Universitario Gregorio Mara\u00f1\u00f3n, Universidad Complutense de Madrid, Madrid, Spain"},{"name":"Instituto de Investigaci\u00f3n Sanitaria del Hospital Gregorio Mara\u00f1\u00f3n, Madrid, Spain"},{"name":"CIBER de Enfermedades Respiratorias, Palma de Mallorca, Spain"},{"name":"Microbiology Department, School of Medicine, Universidad Complutense de Madrid, Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Milagros","family":"Gonz\u00e1lez-Rivera","sequence":"additional","affiliation":[{"name":"Instituto de Investigaci\u00f3n Sanitaria del Hospital Gregorio Mara\u00f1\u00f3n, Madrid, Spain"},{"name":"Sequencing Unit, Hospital General Universitario Gregorio Mara\u00f1\u00f3n, Universidad Complutense de Madrid, Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emilio","family":"Bouza","sequence":"additional","affiliation":[{"name":"Clinical Microbiology and Infectious Diseases Department, Hospital General Universitario Gregorio Mara\u00f1\u00f3n, Universidad Complutense de Madrid, Madrid, Spain"},{"name":"Instituto de Investigaci\u00f3n Sanitaria del Hospital Gregorio Mara\u00f1\u00f3n, Madrid, Spain"},{"name":"CIBER de Enfermedades Respiratorias, Palma de Mallorca, Spain"},{"name":"Microbiology Department, School of Medicine, Universidad Complutense de Madrid, Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jes\u00fas","family":"Guinea","sequence":"additional","affiliation":[{"name":"Clinical Microbiology and Infectious Diseases Department, Hospital General Universitario Gregorio Mara\u00f1\u00f3n, Universidad Complutense de Madrid, Madrid, Spain"},{"name":"Instituto de Investigaci\u00f3n Sanitaria del Hospital Gregorio Mara\u00f1\u00f3n, Madrid, Spain"},{"name":"CIBER de Enfermedades Respiratorias, Palma de Mallorca, Spain"},{"name":"Microbiology Department, School of Medicine, Universidad Complutense de Madrid, Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkq450"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0010080"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.3109\/13693780902717018"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkh507"},{"key":"e_1_3_2_6_2","volume-title":"Approved standard CLSI document M38-A2","author":"Clinical Laboratory Standards Institute","year":"2008","unstructured":"Clinical Laboratory Standards Institute. 2008. 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