{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T07:28:49Z","timestamp":1787729329430,"version":"build-2784847793"},"reference-count":32,"publisher":"American Society for Microbiology","issue":"8","license":[{"start":{"date-parts":[[2013,8,1]],"date-time":"2013-08-01T00:00:00Z","timestamp":1375315200000},"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":[[2013,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Conventional MIC testing of amphotericin B results in narrow MIC ranges challenging the detection of resistant strains. In order to discern amphotericin B pharmacodynamics, the\n                    <jats:italic>in vitro<\/jats:italic>\n                    activity of amphotericin B was studied against\n                    <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Aspergillus<\/jats:named-content>\n                    isolates with the same MICs by using a new\n                    <jats:italic>in vitro<\/jats:italic>\n                    pharmacokinetic\/pharmacodynamic (PK\/PD) model that simulates amphotericin B human plasma levels. Clinical isolates of\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                    ,\n                    <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">A. terreus<\/jats:named-content>\n                    , and\n                    <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">A. flavus<\/jats:named-content>\n                    with the same Clinical and Laboratory Standards Institute modal MICs of 1 mg\/liter were exposed to amphotericin B concentrations following the plasma concentration-time profile after single-bolus administration with\n                    <jats:italic>C<\/jats:italic>\n                    <jats:sub>max<\/jats:sub>\n                    values of 0.6, 1.2, 2.4, and 4.8 mg\/liter. Fungal growth was monitored for up to 72 h based on galactomannan production. Complete growth inhibition was observed only against\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                    with amphotericin B with a\n                    <jats:italic>C<\/jats:italic>\n                    <jats:sub>max<\/jats:sub>\n                    of \u22652.4 mg\/liter. At the lower\n                    <jats:italic>C<\/jats:italic>\n                    <jats:sub>max<\/jats:sub>\n                    values 0.6 and 1.2 mg\/liter, significant growth delays of 34 and 52 h were observed, respectively (\n                    <jats:italic>P<\/jats:italic>\n                    &lt; 0.001). For\n                    <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">A. flavus<\/jats:named-content>\n                    , there was no complete inhibition but a progressive growth delay of 1 to 50 h at an amphotericin B\n                    <jats:italic>C<\/jats:italic>\n                    <jats:sub>max<\/jats:sub>\n                    of 0.6 to 4.8 mg\/liter (\n                    <jats:italic>P<\/jats:italic>\n                    &lt; 0.001). For\n                    <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">A. terreus<\/jats:named-content>\n                    , the growth delay was modest (up to 8 h) at all\n                    <jats:italic>C<\/jats:italic>\n                    <jats:sub>max<\/jats:sub>\n                    s (\n                    <jats:italic>P<\/jats:italic>\n                    &lt; 0.05). The\n                    <jats:italic>C<\/jats:italic>\n                    <jats:sub>max<\/jats:sub>\n                    (95% confidence interval) associated with 50% activity 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                    was 0.60 (0.49 to 0.72) mg\/liter, which was significantly lower than for\n                    <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">A. flavus<\/jats:named-content>\n                    3.06 (2.46 to 3.80) mg\/liter and for\n                    <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">A. terreus<\/jats:named-content>\n                    7.90 (5.20 to 12.29) mg\/liter (\n                    <jats:italic>P<\/jats:italic>\n                    &lt; 0.001). A differential\n                    <jats:italic>in vitro<\/jats:italic>\n                    activity of amphotericin B was found among\n                    <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Aspergillus<\/jats:named-content>\n                    species despite the same MIC in the order\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                    &gt;\n                    <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">A. flavus<\/jats:named-content>\n                    &gt;\n                    <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">A. terreus<\/jats:named-content>\n                    in the\n                    <jats:italic>in vitro<\/jats:italic>\n                    PK\/PD model, possibly reflecting the different concentration- and time-dependent inhibitory\/killing activities amphotericin B exerted against these species.\n                  <\/jats:p>","DOI":"10.1128\/aac.02484-12","type":"journal-article","created":{"date-parts":[[2013,5,29]],"date-time":"2013-05-29T00:58:59Z","timestamp":1369789139000},"page":"3713-3718","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":14,"title":["Single-Dose Pharmacodynamics of Amphotericin B against Aspergillus Species in an\n                    <i>In Vitro<\/i>\n                    Pharmacokinetic\/Pharmacodynamic Model"],"prefix":"10.1128","volume":"57","author":[{"given":"Rafal","family":"Al-Saigh","sequence":"first","affiliation":[{"name":"Clinical Microbiology Laboratory, Attikon Hospital, Medical School, National and Kapodistrian University of Athens, Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Siopi","sequence":"additional","affiliation":[{"name":"Clinical Microbiology Laboratory, Attikon Hospital, Medical School, National and Kapodistrian University of Athens, Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nikolaos","family":"Siafakas","sequence":"additional","affiliation":[{"name":"Clinical Microbiology Laboratory, Attikon Hospital, Medical School, National and Kapodistrian University of Athens, Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aristea","family":"Velegraki","sequence":"additional","affiliation":[{"name":"Mycology Research Lab, Department of Microbiology, Medical School, National and Kapodistrian University of Athens, Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Loukia","family":"Zerva","sequence":"additional","affiliation":[{"name":"Clinical Microbiology Laboratory, Attikon Hospital, Medical School, National and Kapodistrian University of Athens, Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph","family":"Meletiadis","sequence":"additional","affiliation":[{"name":"Clinical Microbiology Laboratory, Attikon Hospital, Medical School, National and Kapodistrian University of Athens, Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1086\/525258"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1053\/jinf.2000.0747"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/45.1.85"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.42.2.282"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.42.4.873"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00686-11"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1592\/phco.20.17.1335.34901"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.46.3.828-833.2002"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dki467"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00662-11"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00549-12"},{"key":"e_1_3_2_13_2","volume-title":"Document M38-A2.28","author":"CLSI","year":"2008","unstructured":"CLSI. 2008. 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