{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T11:51:50Z","timestamp":1790077910390,"version":"4.0.1"},"reference-count":33,"publisher":"American Society for Microbiology","issue":"11","license":[{"start":{"date-parts":[[2014,11,1]],"date-time":"2014-11-01T00:00:00Z","timestamp":1414800000000},"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":[[2014,11]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            We used two established neutropenic murine models of pulmonary aspergillosis and mucormycosis to explore the association between the posaconazole area under the concentration-time curve (AUC)-to-MIC ratio (AUC\/MIC) and treatment outcome. Posaconazole serum pharmacokinetics were verified in infected mice to ensure that the studied doses reflected human exposures with the oral suspension, delayed-release tablet, and intravenous formulations of posaconazole. Sinopulmonary infections were then induced in groups of neutropenic mice with\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            strain 293 (posaconazole MIC, 0.5 mg\/liter) or\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Rhizopus oryzae<\/jats:named-content>\n            strain 969 (posaconazole MIC, 2 mg\/liter) and treated with escalating daily dosages of oral posaconazole, which was designed to achieve AUCs ranging from 1.10 to 392 mg \u00b7 h\/liter. After 5 days of treatment, lung fungal burden was analyzed by quantitative real-time PCR. The relationships of the total drug AUC\/MIC and the treatment response were similar in both models, with 90% effective concentrations (EC\n            <jats:sub>90<\/jats:sub>\n            s) corresponding to an AUC\/MIC threshold of 76 (95% confidence interval [CI], 46 to 102) for strain 293 versus 87 (95% CI, 66 to 101) for strain 969. Using a provisional AUC\/MIC target of &gt;100, these exposures correlated with minimum serum posaconazole concentrations (\n            <jats:italic>C<\/jats:italic>\n            <jats:sub>min<\/jats:sub>\n            s) of 1.25 mg\/liter for strain 293 and 4.0 mg\/liter for strain 969. The addition of deferasirox, but not liposomal amphotericin or caspofungin, improved the activity of a suboptimal posaconazole regimen (AUC\/MIC, 33) in animals with pulmonary mucormycosis. However, no combination was as effective as the high-dose posaconazole monotherapy regimen (AUC\/MIC, 184). Our analysis suggests that posaconazole pharmacodynamics are similar for\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            and\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">R. oryzae<\/jats:named-content>\n            when indexed to pathogen MICs.\n          <\/jats:p>","DOI":"10.1128\/aac.03569-14","type":"journal-article","created":{"date-parts":[[2014,9,3]],"date-time":"2014-09-03T12:54:02Z","timestamp":1409748842000},"page":"6767-6772","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":48,"title":["Comparative Pharmacodynamics of Posaconazole in Neutropenic Murine Models of Invasive Pulmonary Aspergillosis and Mucormycosis"],"prefix":"10.1128","volume":"58","author":[{"given":"Russell E.","family":"Lewis","sequence":"first","affiliation":[{"name":"Department of Medical Sciences and Surgery, University of Bologna, Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nathaniel D.","family":"Albert","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, Infection Control and Employee Health, The University of Texas M. D. Anderson Cancer Center, Houston, Texas, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dimitrios P.","family":"Kontoyiannis","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, Infection Control and Employee Health, The University of Texas M. D. Anderson Cancer Center, Houston, Texas, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.48.2.568-574.2004"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00747-06"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.46.7.2310-2312.2002"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkg020"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01026-09"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00736-10"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1086\/500212"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1111\/1469-0691.12371"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.50.2.658-666.2006"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.2165\/00003088-200544020-00006"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.02686-13"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dks268"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00931-09"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jir023"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01279-12"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00313-13"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkq276"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.47.11.3647-3650.2003"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.50.2.469-473.2006"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01812-10"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01449-06"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01222-09"},{"key":"e_1_3_2_24_2","volume-title":"NCCLS document M39-A2","author":"National Committee for Clinical Laboratory Standards","year":"2002","unstructured":"National Committee for Clinical Laboratory Standards. 2002. Reference method for broth dilution antifungal susceptibility testing of filamentous fungi; approved standard. NCCLS document M39-A2. National Committee for Clinical Laboratory Standards, Wayne, PA."},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1086\/424465"},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.49.2.721-727.2005"},{"key":"e_1_3_2_27_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.48.1.137-142.2004"},{"key":"e_1_3_2_28_2","doi-asserted-by":"crossref","first-page":"S73","DOI":"10.1093\/cid\/cir885","article-title":"Combination therapy for mucormycosis: why, what, and how?","volume":"54","author":"Spellberg B","year":"2012","unstructured":"SpellbergBIbrahimARoilidesELewisRELortholaryOPetrikkosGKontoyiannisDPWalshTJ. 2012. Combination therapy for mucormycosis: why, what, and how? Clin. Infect. Dis. 54(Suppl. 1):S73\u2013S78.","journal-title":"Clin. Infect. Dis."},{"key":"e_1_3_2_29_2","unstructured":"European Committee on Antimicrobial Susceptibility Testing. 2012. Posaconazole and Aspergillus spp.: rationale for the EUCAST clinical breakpoints v 1.0. http:\/\/www.eucast.org\/clinical_breakpoints\/."},{"key":"e_1_3_2_30_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI32338"},{"key":"e_1_3_2_31_2","doi-asserted-by":"publisher","DOI":"10.1097\/QCO.0b013e3283165fd1"},{"key":"e_1_3_2_32_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkr375"},{"key":"e_1_3_2_33_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkr540"},{"key":"e_1_3_2_34_2","volume-title":"Noxafil prescribing information (suspension, delayed release tablet, and intravenous formulation)","author":"Merck & Co, Inc.","year":"2014","unstructured":"Merck & Co, Inc. 2014. Noxafil prescribing information (suspension, delayed release tablet, and intravenous formulation). Merck & Co, Inc., Whitehouse Station, NJ."}],"container-title":["Antimicrobial Agents and Chemotherapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/AAC.03569-14","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/AAC.03569-14","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,2,21]],"date-time":"2022-02-21T22:45:02Z","timestamp":1645483502000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/AAC.03569-14"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2014,11]]},"references-count":33,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2014,11]]}},"alternative-id":["10.1128\/AAC.03569-14"],"URL":"https:\/\/doi.org\/10.1128\/aac.03569-14","relation":{},"ISSN":["0066-4804","1098-6596"],"issn-type":[{"value":"0066-4804","type":"print"},{"value":"1098-6596","type":"electronic"}],"subject":[],"published":{"date-parts":[[2014,11]]},"assertion":[{"value":"2014-06-07","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2014-08-23","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2014-10-16","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}