{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T12:55:10Z","timestamp":1753880110341,"version":"3.41.2"},"reference-count":20,"publisher":"American Society for Microbiology","issue":"5","license":[{"start":{"date-parts":[[2018,5,1]],"date-time":"2018-05-01T00:00:00Z","timestamp":1525132800000},"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":[[2018,5]]},"abstract":"ABSTRACT<\/jats:title>\n \n The lack of a quantifiable marker for echinocandin activity hinders\n in vitro<\/jats:italic>\n pharmacokinetic\/pharmacodynamic (PK\/PD) studies for\n Aspergillus<\/jats:named-content>\n spp. We developed an\n in vitro<\/jats:italic>\n PK\/PD model simulating the pharmacokinetics of anidulafungin and assessing its pharmacodynamics against\n Aspergillus fumigatus<\/jats:named-content>\n with a new, easily quantifiable, sensitive, and reproducible marker. Two clinical\n A. fumigatus<\/jats:named-content>\n isolates previously used in animals (AZN8196 and V52-35) with identical anidulafungin EUCAST (0.03 \u03bcg\/ml) and CLSI (0.015 \u03bcg\/ml) minimal effective concentrations (MEC) and one isolate (strain AFU79728) with an MEC of >16 \u03bcg\/ml were tested in a two-compartment PK\/PD dialysis\/diffusion closed model containing a dialysis membrane (DM) tube inoculated with 10\n 3<\/jats:sup>\n CFU\/ml. During anidulafungin exposure, two types of fungal forms were observed inside the DM tube: floating conidia that were quantified by cultures and aberrant mycelia that were quantified by the vertical height of the mycelia attached on the DM tube. No aberrant mycelia were found for the resistant isolate or in the drug-free controls. An\n in vitro<\/jats:italic>\n exposure-effect relationship was similar to that found in animals using survival as an endpoint, with a free-drug area under the concentration-time curve from 0 to 24 h (\n f<\/jats:italic>\n AUC\n 0\u201324<\/jats:sub>\n ) associated with 50% of maximal activity of 2.21 (range, 1.81 to 2.71) mg \u00b7 h\/liter\n in vitro<\/jats:italic>\n versus 2.62 (range, 1.88 to 3.65) mg \u00b7 h\/liter\n in vivo<\/jats:italic>\n (\n P<\/jats:italic>\n = 0.41). The hillslopes were also similar, with 1.96 versus 1.34 (\n P<\/jats:italic>\n = 0.29). Analysis of each isolate separately showed increased antifungal susceptibility between AZN8196 and V52-35 (\n P<\/jats:italic>\n < 0.001) even though they have the same CLSI and EUCAST MECs, but the strains have two 2-fold dilutions lower MICs using Etest and the XTT {2,3-bis (2-methoxy-4-nitro-5-sulfophenyl)-5-[(phenylamino) carbonyl]-2H-tetrazolium hydroxide} method. Dose fractionation studies with all three echinocandins showed that their activities are best described by\n f<\/jats:italic>\n AUC and not the maximum concentration of free drug (\n fC<\/jats:italic>\n max<\/jats:sub>\n ). The new marker correlated with\n in vivo<\/jats:italic>\n outcome and can be used for\n in vitro<\/jats:italic>\n PK\/PD studies exploring the pharmacodynamics of echinocandins against\n Aspergillus<\/jats:named-content>\n spp.\n <\/jats:p>","DOI":"10.1128\/aac.02322-17","type":"journal-article","created":{"date-parts":[[2018,2,14]],"date-time":"2018-02-14T12:34:23Z","timestamp":1518611663000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":1,"title":["A New Marker of Echinocandin Activity in an\n In Vitro<\/i>\n Pharmacokinetic\/Pharmacodynamic Model Correlates with an Animal Model of Aspergillus fumigatus Infection"],"prefix":"10.1128","volume":"62","author":[{"given":"Joseph","family":"Meletiadis","sequence":"first","affiliation":[{"name":"Clinical Microbiology Laboratory, Attikon University Hospital, Medical School, National and Kapodistrian University of Athens, Athens, Greece"},{"name":"Department of Medical Microbiology and Infectious Diseases, Erasmus Medical Center, Rotterdam, Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria","family":"Siopi","sequence":"additional","affiliation":[{"name":"Clinical Microbiology Laboratory, Attikon University Hospital, Medical School, National and Kapodistrian University of Athens, Athens, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Athanassios","family":"Tsakris","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Medical School, National and Kapodistrian University of Athens, Athens, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Johan W.","family":"Mouton","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology and Infectious Diseases, Erasmus Medical Center, Rotterdam, Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Spyros","family":"Pournaras","sequence":"additional","affiliation":[{"name":"Clinical Microbiology Laboratory, Attikon University Hospital, Medical School, National and Kapodistrian University of Athens, Athens, Greece"},{"name":"Department of Microbiology, Medical School, National and Kapodistrian University of Athens, Athens, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"235","reference":[{"doi-asserted-by":"publisher","key":"e_1_3_1_2_2","DOI":"10.2165\/11585270-000000000-00000"},{"doi-asserted-by":"publisher","key":"e_1_3_1_3_2","DOI":"10.1128\/AAC.00662-11"},{"doi-asserted-by":"publisher","key":"e_1_3_1_4_2","DOI":"10.1093\/jac\/dkw276"},{"doi-asserted-by":"publisher","key":"e_1_3_1_5_2","DOI":"10.1086\/424465"},{"doi-asserted-by":"publisher","key":"e_1_3_1_6_2","DOI":"10.1128\/AAC.01430-12"},{"doi-asserted-by":"publisher","key":"e_1_3_1_7_2","DOI":"10.1086\/589305"},{"doi-asserted-by":"publisher","key":"e_1_3_1_8_2","DOI":"10.2217\/fmb.11.19"},{"doi-asserted-by":"publisher","key":"e_1_3_1_9_2","DOI":"10.1371\/journal.pone.0035478"},{"doi-asserted-by":"publisher","key":"e_1_3_1_10_2","DOI":"10.1093\/nar\/gkm708"},{"doi-asserted-by":"publisher","key":"e_1_3_1_11_2","DOI":"10.1128\/AAC.00699-07"},{"doi-asserted-by":"publisher","key":"e_1_3_1_12_2","DOI":"10.1016\/j.cub.2005.10.001"},{"doi-asserted-by":"publisher","key":"e_1_3_1_13_2","DOI":"10.1002\/jobm.201500759"},{"doi-asserted-by":"publisher","key":"e_1_3_1_14_2","DOI":"10.1128\/AAC.45.10.2845-2855.2001"},{"doi-asserted-by":"publisher","key":"e_1_3_1_15_2","DOI":"10.1128\/AAC.46.6.1857-1869.2002"},{"doi-asserted-by":"publisher","key":"e_1_3_1_16_2","DOI":"10.1128\/AAC.01584-09"},{"unstructured":"Arendrup MC Meletiadis J Mouton JW Lagrou K Hamal P Guinea S Subcommittee on Antimicrobial Testing (AFST) of the ESCMID European Committee for Antimicrobial Testing (EUCAST). 2017. EUCAST definitive document E.DEF 9.3 Method for the determination of broth dilution minimum inhibitory concentrations of antifungal agents for conidia forming moulds. http:\/\/www.eucast.org\/fileadmin\/src\/media\/PDFs\/EUCAST_files\/AFST\/Files\/EUCAST_E_Def_9_3_1_Mould_testing__definitive.pdf.","key":"e_1_3_1_17_2"},{"key":"e_1_3_1_18_2","volume-title":"Reference method for broth dilution antifungal susceptibility testing of filamentous fungi; approved standard","author":"Clinical and Laboratory Standards Institute","year":"2008","unstructured":"Clinical and Laboratory Standards Institute. 2008. Reference method for broth dilution antifungal susceptibility testing of filamentous fungi; approved standard, 2nd ed. CLSI document M38-A2. CLSI, Wayne, PA.","edition":"2"},{"doi-asserted-by":"publisher","key":"e_1_3_1_19_2","DOI":"10.1128\/AAC.00917-07"},{"key":"e_1_3_1_20_2","volume-title":"Abstr 8th Trends Med Mycol","author":"Meletiadis J","year":"2017","unstructured":"Meletiadis J, Siopi M, Kanioura L, J\u00f8rgensen KM, Mouton JW, Arendrup MC. 2017. Optimizing echinocandin susceptibility testing of Aspergillus spp. with the EUCAST E. Def 9.3 method, abstr P014. Abstr 8th Trends Med Mycol, Belgrade, Serbia, 6 to 9 October 2017."},{"doi-asserted-by":"publisher","key":"e_1_3_1_21_2","DOI":"10.1093\/jac\/dku023"}],"container-title":["Antimicrobial Agents and Chemotherapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/AAC.02322-17","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/AAC.02322-17","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,2,21]],"date-time":"2022-02-21T21:09:36Z","timestamp":1645477776000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/AAC.02322-17"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,5]]},"references-count":20,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2018,5]]}},"alternative-id":["10.1128\/AAC.02322-17"],"URL":"https:\/\/doi.org\/10.1128\/aac.02322-17","relation":{},"ISSN":["0066-4804","1098-6596"],"issn-type":[{"type":"print","value":"0066-4804"},{"type":"electronic","value":"1098-6596"}],"subject":[],"published":{"date-parts":[[2018,5]]},"assertion":[{"value":"2017-11-11","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-02-10","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-04-26","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e02322-17"}}