{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T01:29:10Z","timestamp":1787016550335,"version":"build-2736575974"},"reference-count":42,"publisher":"American Society for Microbiology","issue":"11","license":[{"start":{"date-parts":[[2024,11,6]],"date-time":"2024-11-06T00:00:00Z","timestamp":1730851200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/doi.org\/10.1128\/ASMCopyrightv2"},{"start":{"date-parts":[[2024,11,6]],"date-time":"2024-11-06T00:00:00Z","timestamp":1730851200000},"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":[[2024,11,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title\/>\n                    <jats:p>\n                      Large pharmacokinetic (PK) variability of fluconazole has been reported in critically ill patients, but the implications for fluconazole dosing remain unclear. The objectives of this study were to evaluate the population PK of fluconazole and identify appropriate dosage regimens by simulations. This was a retrospective analysis of fluconazole PK data from patients hospitalized in critical care and infectious disease departments. Both parametric and nonparametric population approaches were used. Various loading and maintenance fluconazole doses were evaluated by simulations, with computation of the probabilities of PK\/pharmacodynamic (PD) target attainment (PTA) and cumulative fractions of response (CFR) based on international and local minimum inhibitory concentration (MIC) distributions of\n                      <jats:italic>Candida<\/jats:italic>\n                      sp. Data from 36 critically ill patients and 16 non-critically ill patients were available for model building (\n                      <jats:italic>n<\/jats:italic>\n                      = 202 concentrations). The final model adequately described the data, including the external data set (13 patients). After 24 h of therapy, 65% and 74% of patients had trough and area under the concentration-time curve values below the usual targets. Standard dosages were associated with low PTA for MIC &gt;1 mg\/L at 24 h. Higher loading doses administered two times daily improved PTA. CFR were &gt;90% for\n                      <jats:italic>C. albicans<\/jats:italic>\n                      with standard dosages, while they were very low for\n                      <jats:italic>C. glabrata<\/jats:italic>\n                      , even with high dosages.\n                      <jats:italic>Candida<\/jats:italic>\n                      species and associated MIC distributions strongly influence fluconazole dosage requirements. Higher loading doses may be necessary for the achievement of PK\/PD targets up to MIC breakpoints. The use of fluconazole for invasive\n                      <jats:italic>C. glabrata<\/jats:italic>\n                      infection should be discouraged because of poor PK\/PD target attainment.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1128\/aac.00991-24","type":"journal-article","created":{"date-parts":[[2024,9,26]],"date-time":"2024-09-26T09:01:36Z","timestamp":1727341296000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":9,"title":["Parametric and nonparametric population pharmacokinetic analysis of fluconazole in critically ill patients and dosing simulations for\n                    <i>Candida<\/i>\n                    infections"],"prefix":"10.1128","volume":"68","author":[{"given":"Elodie","family":"Matusik","sequence":"first","affiliation":[{"name":"Hospices Civils de Lyon, GH Nord, Service de Pharmacie, Lyon, France"},{"name":"LBBE \u2013 Laboratoire de Biom\u00e9trie et 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France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tristan","family":"Ferry","sequence":"additional","affiliation":[{"name":"Hospices Civils de Lyon, GH Nord, H\u00f4pital de la Croix-Rousse, Service des Maladies Infectieuses et Tropicales, Centre de R\u00e9f\u00e9rence pour la prise en charge des Infections Ost\u00e9o-Articulaires complexes, Lyon, France"},{"name":"CIRI \u2013 Centre International de Recherche en Infectiologie, Inserm, U1111, Universit\u00e9\u0301 Claude Bernard Lyon 1, CNRS, UMR5308, Ecole Normale Sup\u00e9rieure de Lyon, Univ Lyon, Lyon, France"},{"name":"Univ Lyon, Universit\u00e9 Lyon 1, Facult\u00e9s de M\u00e9decine et de Pharmacie de Lyon, Lyon, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aur\u00e9lien","family":"Millet","sequence":"additional","affiliation":[{"name":"Hospices Civils de Lyon, GH Sud, Laboratoire de Pharmaco-toxicologie, Lyon, 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