{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,2,21]],"date-time":"2025-02-21T09:28:28Z","timestamp":1740130108539,"version":"3.37.3"},"reference-count":25,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2023,11,24]],"date-time":"2023-11-24T00:00:00Z","timestamp":1700784000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004948","name":"Astellas","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004948","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,1,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Pharmacokinetic\/pharmacodynamic (PK\/PD) targets of echinocandins failed to support current clinical breakpoints of Candida parapsilosis as the PTA is low for susceptible isolates despite the good clinical efficacy of echinocandins against these infections. We therefore investigated the effect of micafungin against C. parapsilosis using an in vitro PK\/PD in the presence of 10% human serum.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>Three susceptible (MIC = 0.5\u20132 mg\/L) and one resistant (MIC &amp;gt; 8 mg\/L) C. parapsilosis sensu stricto isolates were tested at two different inocula (104 and 103 cfu\/mL) simulating micafungin human exposures in RPMI and in RPMI + 10% pooled human serum. The exposure\u2013effect relationship tAUC0\u201324\/MIC was described and different PK\/PD targets were determined in order to calculate the PTA for the standard 100 mg IV q24h dose.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>A maximal effect was found at fCmax \u2265 4 mg\/L in RPMI and tCmax \u2265 64 mg\/L (fCmax = 0.08 mg\/L) in the presence of serum for which in vitro PK\/PD targets were 50 times lower. Stasis in the presence of serum was found at 272\u2013240 tAUC0\u201324\/MIC, close to the clinical PK\/PD target (285 tAUC\/MIC), validating the in vitro model. However, the PTA was low for susceptible isolates with EUCAST\/CLSI MICs \u2264 2 mg\/L. Among the different PK\/PD targets investigated, the PK\/PD target 28 tAUC\/MIC associated with 10% of maximal effect with the low inoculum resulted in PTAs \u2265 95% for susceptible isolates with EUCAST\/CLSI MICs \u2264 2 mg\/L.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>A new PK\/PD target was found for micafungin and C. parapsilosis that supports the current clinical breakpoint. This target could be used for assessing echinocandin efficacy against C. parapsilosis.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/jac\/dkad360","type":"journal-article","created":{"date-parts":[[2023,11,24]],"date-time":"2023-11-24T23:24:28Z","timestamp":1700868268000},"page":"157-165","source":"Crossref","is-referenced-by-count":0,"title":["A new PK\/PD target for assessing efficacy of micafungin against <i>Candida parapsilosis<\/i>"],"prefix":"10.1093","volume":"79","author":[{"given":"Maria-Ioanna","family":"Beredaki","sequence":"first","affiliation":[{"name":"Clinical Microbiology Laboratory, Attikon University Hospital, Medical School, National and Kapodistrian University of Athens , Athens , Greece"}],"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"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8869-1509","authenticated-orcid":false,"given":"Joseph","family":"Meletiadis","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"}]}],"member":"286","published-online":{"date-parts":[[2023,11,24]]},"reference":[{"key":"2024010416402957500_dkad360-B1","doi-asserted-by":"crossref","first-page":"e00111-18","DOI":"10.1128\/CMR.00111-18","article-title":"Candida parapsilosis: from genes to the bedside","volume":"32","author":"T\u00f3th","year":"2019","journal-title":"Clin Microbiol Rev"},{"key":"2024010416402957500_dkad360-B2","doi-asserted-by":"crossref","first-page":"e1","DOI":"10.1093\/cid\/civ933","article-title":"Clinical practice guideline for the management of candidiasis: 2016 update 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