{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T22:28:24Z","timestamp":1792794504392,"version":"4.5.0"},"reference-count":31,"publisher":"Oxford University Press (OUP)","issue":"11","license":[{"start":{"date-parts":[[2021,9,4]],"date-time":"2021-09-04T00:00:00Z","timestamp":1630713600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"name":"Japan Research Foundation for Clinical Pharmacology to Y.S. and a scholarship from the Japanese Society of Clinical Pharmacology and Therapeutics","id":[{"id":"https:\/\/ror.org\/02900by63","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,10,11]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>The purpose of this study was to evaluate the influence of augmented renal clearance (ARC) on vancomycin clearance and provide dosage recommendations for paediatric patients with febrile neutropenia following HSCT.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>A population pharmacokinetic analysis was performed based on a two-compartment model structure using a non-linear mixed-effect modelling approach. Monte Carlo simulations were conducted as a target attainment analysis of AUC between 400\u2009mg\u00b7h\/L and 650\u2009mg\u00b7h\/L for MRSA at an MIC of 1\u2009mg\/L.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>A total of 165 paediatric patients and 276 vancomycin serum concentrations were analysed in this study. Age, body weight, estimated glomerular filtration rate (eGFR) and fever (\u226538.0\u00b0C) were identified as factors that significantly influenced vancomycin clearance. The median eGFR of the population was 143\u2009mL\/min\/1.73 m2 and 34% of patients showed an eGFR \u2265160\u2009mL\/min\/1.73 m2, which may be classified as ARC. Our simulations showed that current dosing recommendations result in poor target attainment. In particular, children aged 6\u2009months old to 6\u2009years old with ARC require an initial vancomycin dose up to 35%\u201365% higher than the current dosing guidelines.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>ARC is frequently observed in paediatric patients with post-HSCT febrile neutropenia, resulting in a significant increase in vancomycin clearance. We propose a vancomycin dosing strategy for children with febrile neutropenia following HSCT based on eGFR, age, weight and body temperature.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/jac\/dkab302","type":"journal-article","created":{"date-parts":[[2021,8,2]],"date-time":"2021-08-02T15:18:06Z","timestamp":1627917486000},"page":"2932-2940","source":"Crossref","is-referenced-by-count":23,"title":["Population pharmacokinetics of vancomycin in paediatric patients with febrile neutropenia and augmented renal clearance: development of new dosing recommendations"],"prefix":"10.1093","volume":"76","author":[{"given":"Yuko","family":"Shimamoto","sequence":"first","affiliation":[{"name":"Division of Clinical Pharmacology and Toxicology, Department of Paediatrics, The Hospital for Sick Children, Toronto, Ontario, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6638-8405","authenticated-orcid":false,"given":"Ruud H J","family":"Verstegen","sequence":"additional","affiliation":[{"name":"Division of Clinical Pharmacology and Toxicology, Department of Paediatrics, The Hospital for Sick Children, Toronto, Ontario, Canada"},{"name":"Department of Paediatrics, University of Toronto, Toronto, Ontario, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomoyuki","family":"Mizuno","sequence":"additional","affiliation":[{"name":"Division of Clinical Pharmacology, Cincinnati Children\u2019s Hospital Medical Center, Cincinnati, OH, USA"},{"name":"Department of Pediatrics, College of Medicine, University of Cincinnati, Cincinnati, OH, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tal","family":"Schechter","sequence":"additional","affiliation":[{"name":"Department of Paediatrics, University of Toronto, Toronto, Ontario, Canada"},{"name":"Division of Hematology\/Oncology\/BMT, Department of Paediatrics, The Hospital for Sick Children, Toronto, Ontario, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Upton","family":"Allen","sequence":"additional","affiliation":[{"name":"Department of Paediatrics, University of Toronto, Toronto, Ontario, Canada"},{"name":"Division of Infectious Diseases, Department of Paediatrics, The Hospital for Sick Children, Toronto, Ontario, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shinya","family":"Ito","sequence":"additional","affiliation":[{"name":"Division of Clinical Pharmacology and Toxicology, Department of Paediatrics, The Hospital for Sick Children, Toronto, Ontario, Canada"},{"name":"Department of Paediatrics, University of Toronto, Toronto, Ontario, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2021,9,4]]},"reference":[{"key":"2021101808545531200_dkab302-B1","doi-asserted-by":"crossref","first-page":"126","DOI":"10.1038\/s41409-019-0624-z","article-title":"Death after hematopoietic stem cell transplantation: changes over calendar year time, infections and associated factors","volume":"55","author":"Styczy\u0144ski","year":"2020","journal-title":"Bone Marrow Transplant"},{"key":"2021101808545531200_dkab302-B2","doi-asserted-by":"crossref","first-page":"e56","DOI":"10.1093\/cid\/cir073","article-title":"Clinical practice guideline for the use of antimicrobial agents in neutropenic patients with cancer: 2010 update by the Infectious Diseases Society of America. 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