{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T20:33:28Z","timestamp":1790282008550,"version":"4.1.0"},"reference-count":55,"publisher":"American Society for Microbiology","issue":"5","license":[{"start":{"date-parts":[[2011,5,1]],"date-time":"2011-05-01T00:00:00Z","timestamp":1304208000000},"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":[[2011,5]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Echinocandins have become a first-line therapy for invasive candidiasis (IC). Using phase 3 trial data for patients with IC, pharmacokinetic-pharmacodynamic (PK-PD) relationships for efficacy for micafungin were examined. Micafungin exposures were estimated using a population pharmacokinetic model, and univariable and multivariable logistic regressions were used to identify factors associated with outcome, including the micafungin area under the concentration-time curve (AUC)\/MIC ratio. Monte Carlo simulation was used to evaluate the probability of achieving AUC\/MIC ratios associated with efficacy. Mycological and clinical success rates for evaluable cases were 89.4 and 90.9, respectively. MIC\n                    <jats:sub>50<\/jats:sub>\n                    s and MIC\n                    <jats:sub>90<\/jats:sub>\n                    s for\n                    <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Candida<\/jats:named-content>\n                    species inhibition were 0.008 and 0.5 mg\/liter, respectively. The median AUC\/MIC ratio was 15,511 (range, 41.28 to 98,716). Univariable analyses revealed a significant relationship between the AUC\/MIC ratio and mycological response, with the worst response being among patients with lower (\u22643,000) AUC\/MIC ratios (\n                    <jats:italic>P<\/jats:italic>\n                    = 0.005). For patients with\n                    <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Candida parapsilosis<\/jats:named-content>\n                    , AUC\/MIC ratios of \u2265285 were predictive of a higher mycological response (\n                    <jats:italic>P<\/jats:italic>\n                    = 0.11). Multivariable logistic regression demonstrated the AUC\/MIC ratio, APACHE II score, and history of corticosteroid use to be significant independent predictors of a favorable response. PK-PD target attainment analyses suggested that 76.7% and 100% of patients would achieve an AUC\/MIC ratio of \u22653,000 for an MIC of 0.03 mg\/liter and an AUC\/MIC ratio of \u2265285 for an MIC of &lt;0.5 mg\/liter, respectively. The identification of a lower AUC\/MIC ratio target for\n                    <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">C. parapsilosis<\/jats:named-content>\n                    than other\n                    <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Candida<\/jats:named-content>\n                    species suggests consideration of species-specific echinocandin susceptibility breakpoints and values that are lower than those currently approved by regulatory agencies.\n                  <\/jats:p>","DOI":"10.1128\/aac.01430-10","type":"journal-article","created":{"date-parts":[[2011,2,8]],"date-time":"2011-02-08T00:34:48Z","timestamp":1297125288000},"page":"2113-2121","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":114,"title":["Use of Pharmacokinetic-Pharmacodynamic Analyses To Optimize Therapy with the Systemic Antifungal Micafungin for Invasive Candidiasis or Candidemia"],"prefix":"10.1128","volume":"55","author":[{"given":"David","family":"Andes","sequence":"first","affiliation":[{"name":"University of Wisconsin, Madison, Wisconsin"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul G.","family":"Ambrose","sequence":"additional","affiliation":[{"name":"Institute for Clinical Pharmacodynamics, Latham, New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey P.","family":"Hammel","sequence":"additional","affiliation":[{"name":"Institute for Clinical Pharmacodynamics, Latham, New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Scott A.","family":"Van Wart","sequence":"additional","affiliation":[{"name":"Institute for Clinical Pharmacodynamics, Latham, New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Varsha","family":"Iyer","sequence":"additional","affiliation":[{"name":"Institute for Clinical Pharmacodynamics, Latham, New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel K.","family":"Reynolds","sequence":"additional","affiliation":[{"name":"Institute for Clinical Pharmacodynamics, Latham, New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Donald N.","family":"Buell","sequence":"additional","affiliation":[{"name":"Astellas Pharma Global Development, Deerfield, Illinois"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura L.","family":"Kovanda","sequence":"additional","affiliation":[{"name":"Astellas Pharma Global Development, Deerfield, Illinois"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sujata M.","family":"Bhavnani","sequence":"additional","affiliation":[{"name":"Institute for Clinical Pharmacodynamics, Latham, New York"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","volume-title":"Proceedings from Issues in Antibacterial Resistance and Device and Drug Development","author":"Ambrose P. 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Food and Drug Administration, National Institute of Allergy and Infectious Diseases, and Infectious Diseases Society of America, Washington, DC. http:\/\/www.fda.gov\/Drugs\/NewsEvents\/ucm211146.htm."},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1086\/510079"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.47.4.1179-1186.2003"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.47.12.3935-3941.2003"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.46.6.1665-1670.2002"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01061-07"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.47.4.1187-1192.2003"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00478-08"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01584-09"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1007\/s15010-002-2131-0"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00116-08"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1086\/501020"},{"key":"e_1_3_3_14_2","volume-title":"Approved guideline M23-A3","author":"Clinical and Laboratory Standards Institute.","year":"2008","unstructured":"Clinical and Laboratory Standards Institute. 2008. 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