{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T17:02:22Z","timestamp":1788282142639,"version":"build-2803163510"},"reference-count":18,"publisher":"American Society for Microbiology","issue":"2","license":[{"start":{"date-parts":[[2012,2,1]],"date-time":"2012-02-01T00:00:00Z","timestamp":1328054400000},"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":[[2012,2]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            Hematogenous\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Candida<\/jats:named-content>\n            meningoencephalitis (HCME) is a serious infection in premature neonates. Anidulafungin is an echinocandin antifungal agent with potent activity against\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Candida<\/jats:named-content>\n            spp., but its efficacy and optimal regimens for human neonates with HCME are not known. A well-validated rabbit model of HCME was used to define pharmacokinetic-pharmacodynamic (PK-PD) relationships of anidulafungin. A mathematical model was fitted to the entire data set. The experimental data were bridged to humans. A population PK model was fitted to the data from human neonates receiving anidulafungin receiving a loading dose of 3 mg\/kg, followed by 1.5 mg\/kg\/day. Monte Carlo simulations were performed to identify candidate anidulafungin regimens for humans. All untreated rabbits succumbed by \u226496 h postinoculation. The PK of anidulafungin was linear with dose-dependent penetration into the cerebrum. Anidulafungin exerted a rapid antifungal effect that was apparent in the first dosing interval. Near-maximal antifungal activity was observed with dosages of 10 to 20 mg\/kg\/day. The bridging studies suggested that the current regimen of first 3 mg\/kg, followed by 1.5 mg\/kg\/day, is suboptimal. Higher dosages were associated with progressively greater antifungal effect. Anidulafungin is effective for the treatment of experimental HCME. Higher dosages than those currently used for clinical care are required for maximal antifungal effect.\n          <\/jats:p>","DOI":"10.1128\/aac.05826-11","type":"journal-article","created":{"date-parts":[[2011,11,30]],"date-time":"2011-11-30T02:31:59Z","timestamp":1322620319000},"page":"708-714","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":37,"title":["Anidulafungin for Neonatal Hematogenous Candida Meningoencephalitis: Identification of Candidate Regimens for Humans Using a Translational Pharmacological Approach"],"prefix":"10.1128","volume":"56","author":[{"given":"Peter A.","family":"Warn","sequence":"first","affiliation":[{"name":"The University of Manchester, Manchester Academic Health Science Centre, NIHR Translational Research Facility in Respiratory Medicine, University Hospital of South Manchester NHS Foundation Trust, Manchester, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joanne","family":"Livermore","sequence":"additional","affiliation":[{"name":"The University of Manchester, Manchester Academic Health Science Centre, NIHR Translational Research Facility in Respiratory Medicine, University Hospital of South Manchester NHS Foundation Trust, Manchester, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susan","family":"Howard","sequence":"additional","affiliation":[{"name":"The University of Manchester, Manchester Academic Health Science Centre, NIHR Translational Research Facility in Respiratory Medicine, University Hospital of South Manchester NHS Foundation Trust, Manchester, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timothy W.","family":"Felton","sequence":"additional","affiliation":[{"name":"The University of Manchester, Manchester Academic Health Science Centre, NIHR Translational Research Facility in Respiratory Medicine, University Hospital of South Manchester NHS Foundation Trust, Manchester, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew","family":"Sharp","sequence":"additional","affiliation":[{"name":"The University of Manchester, Manchester Academic Health Science Centre, NIHR Translational Research Facility in Respiratory Medicine, University Hospital of South Manchester NHS Foundation Trust, Manchester, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lea","family":"Gregson","sequence":"additional","affiliation":[{"name":"The University of Manchester, Manchester Academic Health Science Centre, NIHR Translational Research Facility in Respiratory Medicine, University Hospital of South Manchester NHS Foundation Trust, Manchester, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joanne","family":"Goodwin","sequence":"additional","affiliation":[{"name":"The University of Manchester, Manchester Academic Health Science Centre, NIHR Translational Research Facility in Respiratory Medicine, University Hospital of South Manchester NHS Foundation Trust, Manchester, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruta","family":"Petraitiene","sequence":"additional","affiliation":[{"name":"Weill Medical College of Cornell University, New York, New York, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vidmantas","family":"Petraitis","sequence":"additional","affiliation":[{"name":"Weill Medical College of Cornell University, New York, New York, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Cohen-Wolkowiez","sequence":"additional","affiliation":[{"name":"Department of Pediatrics and Duke Clinical Research Institute, Duke University, Durham, North Carolina, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas J.","family":"Walsh","sequence":"additional","affiliation":[{"name":"Weill Medical College of Cornell University, New York, New York, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"Jr.","given":"Daniel K.","family":"Benjamin","sequence":"additional","affiliation":[{"name":"Department of Pediatrics and Duke Clinical Research Institute, Duke University, Durham, North Carolina, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William W.","family":"Hope","sequence":"additional","affiliation":[{"name":"The University of Manchester, Manchester Academic Health Science Centre, NIHR Translational Research Facility in Respiratory Medicine, University Hospital of South Manchester NHS Foundation Trust, Manchester, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"crossref","first-page":"E18","DOI":"10.1111\/j.1469-0691.2011.03647.x","article-title":"EUCAST technical note on anidulafungin","volume":"17","author":"Arendrup MC","unstructured":"ArendrupMC. EUCAST technical note on anidulafungin. Clin. Microbiol. Infect. 17:E18\u2013E20.","journal-title":"Clin. Microbiol. Infect"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.50.2.632-638.2006"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1542\/peds.2004-2292"},{"key":"e_1_3_2_5_2","unstructured":"Clinical and Laboratory Standards Institute. 2008. Reference method for broth dilution antifungal susceptibility testing of yeasts 3rd ed.  Approved standard M27\u2013A3(28). Clinical and Laboratory Standards Institute Wayne PA."},{"key":"e_1_3_2_6_2","doi-asserted-by":"crossref","first-page":"702","DOI":"10.1038\/clpt.2011.26","article-title":"Safety and pharmacokinetics of multiple-dose anidulafungin in infants and neonates","volume":"89","author":"Cohen-Wolkowiez M","unstructured":"Cohen-WolkowiezM. Safety and pharmacokinetics of multiple-dose anidulafungin in infants and neonates. Clin. Pharmacol. Ther. 89:702\u2013707.","journal-title":"Clin. 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Biomedical Simulations Resource, Los Angeles, CA."},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(03)14472-8"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1177\/0091270004265644"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1086\/315643"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.45.10.2845-2855.2001"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-0691.2009.02913.x"},{"key":"e_1_3_2_13_2","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1086\/524063","article-title":"The pharmacokinetics and pharmacodynamics of micafungin in experimental hematogenous Candida meningo-encephalitis: implications for echinocandin therapy in neonates","volume":"197","author":"Hope WW","year":"2008","unstructured":"HopeWW. 2008. The pharmacokinetics and pharmacodynamics of micafungin in experimental hematogenous Candida meningo-encephalitis: implications for echinocandin therapy in neonates. J. Infect. Dis. 197:163\u2013171.","journal-title":"J. Infect. Dis."},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00398-07"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01679-09"},{"key":"e_1_3_2_16_2","first-page":"389","volume-title":"Proceedings of the 14th IEEE Computer Society Meeting","author":"Leary R","year":"2001","unstructured":"LearyR JelliffeR SchumitzkyA van GuilderM. 2001. An adaptive grid, non-parametric approach to pharmacokinetic and dynamic (PK\/PD) models, p 389\u2013394. 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