{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T14:48:31Z","timestamp":1791557311907,"version":"4.3.4"},"reference-count":52,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2018,2,14]],"date-time":"2018-02-14T00:00:00Z","timestamp":1518566400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Mycoses"],"published-print":{"date-parts":[[2018,5]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p>Fluconazole is the most commonly used antifungal agent for both the treatment of cryptococcal meningitis, and for prophylaxis against the disease. However, its prolonged use has the potential to exert selection pressure in favour of fluconazole\u2010resistant strains. We evaluated the prevalence of fluconazole resistance in<jats:italic>Cryptococcus<\/jats:italic>spp. clinical isolates in 29 studies from 1988 to May 2017 included in<jats:styled-content style=\"fixed-case\">EMBASE<\/jats:styled-content>and<jats:styled-content style=\"fixed-case\">MEDLINE<\/jats:styled-content>databases. A total of 4995<jats:italic>Cryptococcus<\/jats:italic>isolates from 3210 patients constituted this study; 248 (5.0%) of the isolates from relapsed episodes of cryptococcosis were included in this analysis. Eleven (38%) of the studies used minimum inhibitory concentrations (<jats:styled-content style=\"fixed-case\">MIC<\/jats:styled-content>s) breakpoints of \u226564\u00a0\u03bcg\/mL to define fluconazole resistance, 6 (21%) used \u226532\u00a0\u03bcg\/mL, 11 (38%) used \u226516\u00a0\u03bcg\/mL and 1 (3%) used \u226420\u00a0\u03bcg\/mL. Overall, mean prevalence of fluconazole resistance was 12.1% (95% confidence interval [<jats:styled-content style=\"fixed-case\">CI<\/jats:styled-content>]: 6.7\u201017.6) for all isolates (n\u00a0=\u00a04995). Mean fluconazole resistance was 10.6% (95%<jats:styled-content style=\"fixed-case\">CI<\/jats:styled-content>: 5.5\u201015.6) for the incident isolates (n\u00a0=\u00a04747) and 24.1% (95%<jats:styled-content style=\"fixed-case\">CI<\/jats:styled-content>: \u22123.1\u201051.2) for the relapse isolates (n\u00a0=\u00a0248). Of the 4995 isolates, 936 (18.7%) had<jats:styled-content style=\"fixed-case\">MIC<\/jats:styled-content>s above the ecological cut\u2010off value. Fluconazole resistance appears to be an issue in<jats:italic>Cryptococcus<\/jats:italic>isolates from patients with relapses. It remains unclear whether relapses occur due to resistance or other factors. There is an urgent need to establish antifungal breakpoints for<jats:italic>Cryptococcus<\/jats:italic>spp.<\/jats:p>","DOI":"10.1111\/myc.12747","type":"journal-article","created":{"date-parts":[[2018,1,29]],"date-time":"2018-01-29T22:10:02Z","timestamp":1517263802000},"page":"290-297","source":"Crossref","is-referenced-by-count":153,"title":["A systematic review of fluconazole resistance in clinical isolates of<i>Cryptococcus<\/i>species"],"prefix":"10.1111","volume":"61","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4515-8517","authenticated-orcid":false,"given":"Felix","family":"Bongomin","sequence":"first","affiliation":[{"name":"Division of Infection, Immunity and Respiratory Medicine Faculty of Biology, Medicine and Health The University of Manchester Manchester UK"},{"name":"The National Aspergillosis Centre &amp; NHS Mycology Reference Centre\u2010Manchester ECMM Center of Excellence in Clinical and Laboratory Mycology and Clinical Studies Wythenshawe Hospital Manchester University NHS Foundation Trust Manchester UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1488-3345","authenticated-orcid":false,"given":"Rita O.","family":"Oladele","sequence":"additional","affiliation":[{"name":"Division of Infection, Immunity and Respiratory Medicine Faculty of Biology, Medicine and Health The University of Manchester Manchester UK"},{"name":"Department of Medical Microbiology and Parasitology College of Medicine University of Lagos Lagos Nigeria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7027-4598","authenticated-orcid":false,"given":"Sara","family":"Gago","sequence":"additional","affiliation":[{"name":"Division of Infection, Immunity and Respiratory Medicine Faculty of Biology, Medicine and Health The University of Manchester Manchester UK"},{"name":"Manchester Fungal Infection Group Division of Infection, Immunity and Respiratory Medicine Faculty of Biology, Medicine and Health The University of Manchester Manchester UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caroline B.","family":"Moore","sequence":"additional","affiliation":[{"name":"Division of Infection, Immunity and Respiratory Medicine Faculty of Biology, Medicine and Health The University of Manchester Manchester UK"},{"name":"The National Aspergillosis Centre &amp; NHS Mycology Reference Centre\u2010Manchester ECMM Center of Excellence in Clinical and Laboratory Mycology and Clinical Studies Wythenshawe Hospital Manchester University NHS Foundation Trust Manchester UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Malcolm D.","family":"Richardson","sequence":"additional","affiliation":[{"name":"Division of Infection, Immunity and Respiratory Medicine Faculty of Biology, Medicine and Health The University of Manchester Manchester UK"},{"name":"The National Aspergillosis Centre &amp; NHS Mycology Reference Centre\u2010Manchester ECMM Center of Excellence in Clinical and Laboratory Mycology and Clinical Studies Wythenshawe Hospital Manchester University NHS Foundation Trust Manchester UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2018,2,14]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0163036"},{"key":"e_1_2_7_3_1","first-page":"1","article-title":"Global burden of disease of HIV\u2010associated cryptococcal meningitis: an updated analysis","volume":"3099","author":"Rajasingham R","year":"2017","journal-title":"Lancet Infect Dis"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1097\/QAD.0b013e328322ffac"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1080\/1120009X.1990.11738981"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/173.5.1216"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1086\/649858"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1110404"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1086\/516372"},{"key":"e_1_2_7_10_1","unstructured":"World Health Organization HIV\/AIDS Program.Rapid advice: diagnosis prevention and management of cryptococcal disease in HIV\u2010infected adults adolescents and children. 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