{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T11:58:07Z","timestamp":1791979087540,"version":"4.4.0"},"reference-count":32,"publisher":"SAGE Publications","issue":"7","license":[{"start":{"date-parts":[[2020,11,4]],"date-time":"2020-11-04T00:00:00Z","timestamp":1604448000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Ann Pharmacother"],"published-print":{"date-parts":[[2021,7]]},"abstract":"<jats:sec>\n                    <jats:title>Background:<\/jats:title>\n                    <jats:p>The optimal daptomycin dose for vancomycin-resistant Enterococcus faecium remains unclear. Dosing of 8 to 12 mg\/kg\/d has been recommended to improve outcomes, but literature suggests fixed dosing may improve methicillin-resistant Staphylococcus aureus bacteremia pharmacodynamic (PD) targets.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective:<\/jats:title>\n                    <jats:p>This study sought to evaluate weight-based versus fixed dosing of daptomycin based on pharmacokinetic and PD (PK-PD) targets in vancomycin-resistant E faecium bacteremia.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>\n                      PK-PD analyses were conducted using previously published PK models for daptomycin. Probability of target attainment (PTA) was assessed for 8 to 12 mg\/kg\/d and various fixed doses. The percentage of simulated participants who achieved a free area under the concentration-time curve from 0 to 24 hours to minimum inhibitory concentration ratio ( fAUC\n                      <jats:sub>0-24<\/jats:sub>\n                      \/MIC) &gt;27.43 for susceptible dose-dependent (SDD) MICs and the probability of a minimum concentration ( C\n                      <jats:sub>min<\/jats:sub>\n                      ) &gt; 24.3 mg\/L were calculated.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>\n                      At MICs \u22642 mg\/L, fixed doses had the best overall PTA. At the SDD breakpoint of 4 mg\/L, all weight-based doses had &lt;60% PTA. A fixed dose of 1500 mg\/d was necessary for &gt;\/= 90% PTA at higher MICs considered SDD; however, this dose had elevated risks of C\n                      <jats:sub>min<\/jats:sub>\n                      \u226524.3 mg\/L.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion and Relevance:<\/jats:title>\n                    <jats:p>Fixed doses were more likely to achieve a fAUC\/MIC of 27.43 than weight-based doses up to 12 mg\/kg\/d. However, fixed doses necessary for 90% PTA against SDD isolates with higher MICs were associated with elevated risks of toxicity. A reevaluation of Clinical Laboratory Standards Institute breakpoints may need to be considered, with an emphasis on lowering the SDD breakpoint to 1 mg\/L.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/1060028020971216","type":"journal-article","created":{"date-parts":[[2020,11,5]],"date-time":"2020-11-05T01:55:06Z","timestamp":1604541306000},"page":"846-855","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":6,"title":["A Pharmacokinetic-Pharmacodynamic Analysis to Dose Optimize Daptomycin in Vancomycin-Resistant\n                    <i>Enterococcus faecium<\/i>\n                    : Is the Answer Fixed Dosing or Lowering Breakpoints?"],"prefix":"10.1177","volume":"55","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6497-7908","authenticated-orcid":false,"given":"Jill M.","family":"Butterfield-Cowper","sequence":"first","affiliation":[{"name":"HealthTrust Supply Chain, Richmond, VA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2020,11,4]]},"reference":[{"key":"bibr1-1060028020971216","unstructured":"Cubicin. 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