{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,24]],"date-time":"2025-11-24T10:00:41Z","timestamp":1763978441612,"version":"3.41.0"},"reference-count":15,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2025,4,3]],"date-time":"2025-04-03T00:00:00Z","timestamp":1743638400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"name":"Australian Government Research Training Program Scholarship"},{"name":"NHMRC Investigator","award":["APP2017661"],"award-info":[{"award-number":["APP2017661"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,6,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Transcatheter aortic valve implantation (TAVI) is a less invasive alternative to surgical valve replacement for aortic stenosis. Infective endocarditis, most often caused by enterococci, is a significant post-procedural complication. Cefazolin has been the most frequently utilized agent for TAVI procedural prophylaxis, although recent guidelines suggest addition of an agent with enterococcal activity. Optimizing antimicrobial prophylaxis is important but little is known about antibiotic pharmacokinetics (PK) in this procedure.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Objectives<\/jats:title>\n                  <jats:p>To define the population PK profile of prophylactic cefazolin in TAVI procedures and determine appropriateness for use.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>Adult patients receiving cefazolin prophylaxis for TAVI were enrolled. Serum was collected at four timepoints periprocedurally for analysis of cefazolin concentrations. Population PK analysis and Monte Carlo simulation was performed. Fractional target attainment (FTA) against MIC distributions for common pathogens was performed.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Three hundred and fifty-nine plasma cefazolin concentrations (188 total, 171 unbound) from 50 participants were used for model development. PTA for a 2\u2005g dose of cefazolin and a procedure of 2\u2005h duration was &amp;gt;90% for organisms with an MIC up to 8\u2005mg\/L. FTA was 100% for MSSA at all examined procedure durations and estimated glomerular filtration rate levels. FTAs for Staphylococcus epidermidis and Enterococcus faecalis, based on limited MIC data, were predominantly subthreshold.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>This study found a 2\u2005g dose of cefazolin achieved target exposure for MSSA but was subthreshold for other pathogens.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/jac\/dkaf108","type":"journal-article","created":{"date-parts":[[2025,3,20]],"date-time":"2025-03-20T17:19:12Z","timestamp":1742491152000},"page":"1604-1612","source":"Crossref","is-referenced-by-count":1,"title":["Population pharmacokinetics and optimized prophylaxis dosing of cefazolin during transcatheter aortic valve implantation"],"prefix":"10.1093","volume":"80","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4393-3308","authenticated-orcid":false,"given":"C","family":"Robson","sequence":"first","affiliation":[{"name":"Monash Infectious Diseases, Monash Health , Melbourne ,","place":["Australia"]},{"name":"Faculty of Medicine, Nursing and Health Sciences, Monash University , Melbourne ,","place":["Australia"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"X","family":"Liu","sequence":"additional","affiliation":[{"name":"University of Queensland Centre for Clinical Research, Faculty of Health, Medicine and Behavioural Sciences, The University of Queensland , Brisbane ,","place":["Australia"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"O","family":"Al-Mukhtar","sequence":"additional","affiliation":[{"name":"Monash Heart, Monash Health , Melbourne ,","place":["Australia"]},{"name":"Department of Cardiology, Western Health , Melbourne ,","place":["Australia"]},{"name":"Department of Cardiology, Epworth HealthCare , Melbourne ,","place":["Australia"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2392-9854","authenticated-orcid":false,"given":"S C","family":"Wallis","sequence":"additional","affiliation":[{"name":"University of Queensland Centre for Clinical Research, Faculty of Health, Medicine and Behavioural Sciences, The University of Queensland , Brisbane ,","place":["Australia"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"H","family":"Won","sequence":"additional","affiliation":[{"name":"University of Queensland Centre for Clinical Research, Faculty of Health, Medicine and Behavioural Sciences, The University of Queensland , Brisbane ,","place":["Australia"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J","family":"Ordonez","sequence":"additional","affiliation":[{"name":"University of Queensland Centre for Clinical Research, Faculty of Health, Medicine and Behavioural Sciences, The University of Queensland , Brisbane ,","place":["Australia"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"R","family":"Gooley","sequence":"additional","affiliation":[{"name":"Monash Heart, Monash Health , Melbourne ,","place":["Australia"]},{"name":"Victorian Heart Institute, Monash University , Melbourne ,","place":["Australia"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"R L","family":"Stuart","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Nursing and Health Sciences, Monash University , Melbourne ,","place":["Australia"]},{"name":"South Eastern Public Health Unit, Monash Health , Melbourne ,","place":["Australia"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"S J","family":"Nicholls","sequence":"additional","affiliation":[{"name":"Monash Heart, Monash Health , Melbourne ,","place":["Australia"]},{"name":"Victorian Heart Institute, Monash University , Melbourne ,","place":["Australia"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J A","family":"Roberts","sequence":"additional","affiliation":[{"name":"University of Queensland Centre for Clinical Research, Faculty of Health, Medicine and Behavioural Sciences, The University of Queensland , Brisbane ,","place":["Australia"]},{"name":"Herston Infectious Diseases Institute (HeIDI), Metro North Health , Brisbane ,","place":["Australia"]},{"name":"Departments of Pharmacy and Intensive Care Medicine, Royal Brisbane and Women\u2019s Hospital , Brisbane ,","place":["Australia"]},{"name":"UR UM 103, University of Montpellier, Division of Anaesthesia Critical Care and Emergency and Pain Medicine, Nimes University Hospital , Nimes ,","place":["France"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6515-2118","authenticated-orcid":false,"given":"B A","family":"Rogers","sequence":"additional","affiliation":[{"name":"Monash Infectious Diseases, Monash Health , Melbourne ,","place":["Australia"]},{"name":"Faculty of Medicine, Nursing and Health Sciences, Monash University , Melbourne ,","place":["Australia"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2025,4,3]]},"reference":[{"key":"2025060219525249700_dkaf108-B1","doi-asserted-by":"publisher","first-page":"1695","DOI":"10.1056\/NEJMoa1814052","article-title":"Transcatheter aortic-valve replacement with a balloon-expandable valve in low-risk patients","volume":"380","author":"Mack","year":"2019","journal-title":"N Engl J Med"},{"key":"2025060219525249700_dkaf108-B2","doi-asserted-by":"publisher","first-page":"1706","DOI":"10.1056\/NEJMoa1816885","article-title":"Transcatheter aortic-valve replacement with a self-expanding valve in low-risk patients","volume":"380","author":"Popma","year":"2019","journal-title":"N Engl J Med"},{"key":"2025060219525249700_dkaf108-B3","doi-asserted-by":"publisher","first-page":"1790","DOI":"10.1056\/NEJMoa1400590","article-title":"Transcatheter aortic-valve replacement with a self-expanding prosthesis","volume":"370","author":"Adams","year":"2014","journal-title":"N Engl J Med"},{"key":"2025060219525249700_dkaf108-B4","doi-asserted-by":"publisher","first-page":"1321","DOI":"10.1056\/NEJMoa1700456","article-title":"Surgical or transcatheter aortic-valve replacement in intermediate-risk patients","volume":"376","author":"Reardon","year":"2017","journal-title":"N Engl J Med"},{"key":"2025060219525249700_dkaf108-B5","doi-asserted-by":"publisher","first-page":"e0225077","DOI":"10.1371\/journal.pone.0225077","article-title":"Infective endocarditis post-transcatheter aortic valve implantation (TAVI), microbiological profile and clinical outcomes: a systematic review","volume":"15","author":"Khan","year":"2020","journal-title":"PLoS One"},{"key":"2025060219525249700_dkaf108-B6","doi-asserted-by":"publisher","first-page":"3020","DOI":"10.1016\/j.jacc.2020.04.044","article-title":"Infective endocarditis after transcatheter aortic valve replacement","volume":"75","author":"Stortecky","year":"2020","journal-title":"J Am Coll Cardiol"},{"key":"2025060219525249700_dkaf108-B7","doi-asserted-by":"publisher","first-page":"1566","DOI":"10.1161\/CIRCULATIONAHA.114.014089","article-title":"Infective endocarditis after transcatheter aortic valve implantation: results from a large multicenter registry","volume":"131","author":"Amat-Santos","year":"2015","journal-title":"Circulation"},{"key":"2025060219525249700_dkaf108-B8","doi-asserted-by":"publisher","first-page":"1135","DOI":"10.4244\/EIJ-D-19-00993","article-title":"A review of recommendations for infective endocarditis prevention in patients undergoing transcatheter aortic valve implantation","volume":"16","author":"Conen","year":"2021","journal-title":"EuroIntervention"},{"key":"2025060219525249700_dkaf108-B9","doi-asserted-by":"publisher","first-page":"3948","DOI":"10.1093\/eurheartj\/ehad193","article-title":"2023 ESC guidelines for the management of endocarditis","volume":"44","author":"Delgado","year":"2023","journal-title":"Eur Heart J"},{"key":"2025060219525249700_dkaf108-B10","doi-asserted-by":"publisher","first-page":"2980","DOI":"10.1093\/jac\/dkae318","article-title":"Population pharmacokinetics of unbound cefazolin in infected hospitalized patients requiring intermittent high-flux haemodialysis: can a three-times-weekly post-dialysis dosing regimen provide optimal treatment?","volume":"79","author":"Duke","year":"2024","journal-title":"J Antimicrob Chemother"},{"author":"FDA, Center for Drug Evaluation and Research","key":"2025060219525249700_dkaf108-B11"},{"author":"EUCAST","key":"2025060219525249700_dkaf108-B12"},{"key":"2025060219525249700_dkaf108-B13","doi-asserted-by":"publisher","first-page":"1949","DOI":"10.1056\/NEJMoa2307447","article-title":"Transcatheter aortic-valve replacement in low-risk patients at five years","volume":"389","author":"Mack","year":"2023","journal-title":"N Engl J Med"},{"key":"2025060219525249700_dkaf108-B14","doi-asserted-by":"publisher","first-page":"3138","DOI":"10.1007\/s11695-022-06196-5","article-title":"Prophylactic cefazolin dosing in obesity\u2014a systematic review","volume":"32","author":"Coates","year":"2022","journal-title":"Obes Surg"},{"key":"2025060219525249700_dkaf108-B15","doi-asserted-by":"publisher","first-page":"1221","DOI":"10.1586\/14787210.2014.956092","article-title":"Mechanisms of antibiotic resistance in enterococci","volume":"12","author":"Miller","year":"2014","journal-title":"Expert Rev Anti Infect Ther"}],"container-title":["Journal of Antimicrobial Chemotherapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/jac\/article-pdf\/80\/6\/1604\/62850793\/dkaf108.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jac\/article-pdf\/80\/6\/1604\/62850793\/dkaf108.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,6,2]],"date-time":"2025-06-02T23:52:59Z","timestamp":1748908379000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jac\/article\/80\/6\/1604\/8104822"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,4,3]]},"references-count":15,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2025,4,3]]},"published-print":{"date-parts":[[2025,6,3]]}},"URL":"https:\/\/doi.org\/10.1093\/jac\/dkaf108","relation":{},"ISSN":["0305-7453","1460-2091"],"issn-type":[{"type":"print","value":"0305-7453"},{"type":"electronic","value":"1460-2091"}],"subject":[],"published-other":{"date-parts":[[2025,6]]},"published":{"date-parts":[[2025,4,3]]}}}