{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T04:43:00Z","timestamp":1791434580029,"version":"4.3.3"},"reference-count":52,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2023,8,28]],"date-time":"2023-08-28T00:00:00Z","timestamp":1693180800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["accpjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Pharmacotherapy"],"published-print":{"date-parts":[[2023,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Vancomycin dosing tailored for newborns is challenging due to the significant influence of maturation and organ function on pharmacokinetics. Population pharmacokinetic (popPK) models can be used to improve target attainment in neonates.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>The primary objective was to derive and evaluate a popPK model of intravenous vancomycin for neonates. Second, the predictive performance of this popPK model was compared with published popPK models.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This is a retrospective cohort study of neonates admitted to the neonatal intensive care unit receiving intravenous vancomycin. A popPK model was derived with 70% of the dataset using a nonlinear mixed effects modeling method. The predictive performance of the current popPK model was validated and compared with 22 published popPK models using the remaining 30% of the dataset. Monte Carlo simulations (MCS) were performed to derive optimal dosing regimens to treat neonatal sepsis caused by coagulase\u2010negative staphylococci (CoNS).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Among 655 vancomycin courses from 448 neonates, 78% of vancomycin trough concentrations were outside target range (10\u201315\u2009mg\/L) for central nervous system infections and 43% were outside target range (5\u201312\u2009mg\/L) for other infections using the institution's vancomycin dosing. A one\u2010compartment model best described the observed data with a mean clearance of 0.11\u2009\u00b1\u20090.03\u2009L\/kg\/h and volume of distribution (V) of 1.02\u2009\u00b1\u20090.08\u2009L\/kg. Body weight (WT), postmenstrual age (PMA), and serum creatinine (SCr) were significant covariates associated with clearance (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001) and body WT was a significant covariate associated with V (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.009). Our study's popPK model has similar or better accuracy and precision than other published models. MCS\u2010derived vancomycin doses from the validated model achieved &gt;90% target attainment for a steady state through target range of 10\u201315\u2009mg\/L in the majority of PMA and SCr categories (78%) to treat CoNS sepsis.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>A vancomycin dosing guideline derived from a validated popPK model in neonates with CoNS sepsis is recommended to improve target attainment.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/phar.2865","type":"journal-article","created":{"date-parts":[[2023,8,14]],"date-time":"2023-08-14T01:14:50Z","timestamp":1691975690000},"page":"1262-1276","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Using population pharmacokinetics to optimize initial vancomycin dosing guidelines for neonates to treat sepsis caused by coagulase\u2010negative staphylococcus"],"prefix":"10.1002","volume":"43","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4268-0879","authenticated-orcid":false,"given":"Erin","family":"Chung","sequence":"first","affiliation":[{"name":"Department of Pharmacy The Hospital for Sick Children  Toronto Ontario Canada"},{"name":"Leslie Dan Faculty of Pharmacy University of Toronto  Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8692-8616","authenticated-orcid":false,"given":"Winnie","family":"Seto","sequence":"additional","affiliation":[{"name":"Department of Pharmacy The Hospital for Sick Children  Toronto Ontario Canada"},{"name":"Leslie Dan Faculty of Pharmacy University of Toronto  Toronto Ontario Canada"},{"name":"Child Health Evaluative Sciences SickKids Research Institute  Toronto Ontario Canada"},{"name":"Institute of Health Policy, Management and Evaluation, Dalla Lana School of Public Health University of Toronto  Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,8,28]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1128\/JCM.00967-10"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01908-13"},{"key":"e_1_2_8_4_1","first-page":"476","article-title":"Challenges of vancomycin dosing and therapeutic monitoring in neonates","volume":"6","author":"Pham JT","year":"2020","journal-title":"J Pediatr Pharmacol Ther"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40262-021-01027-9"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.31.1.52"},{"key":"e_1_2_8_7_1","volume-title":"2020 SickKids Drug Handbook & Formulary","author":"Lau E","year":"2020"},{"key":"e_1_2_8_8_1","unstructured":"HuttonL ChungE LimSH et al.A retrospective study of extended interval vancomycin dosing in neonates.2015. \"Report\"."},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1093\/ajhp\/zxaa036"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/cir529"},{"key":"e_1_2_8_11_1","first-page":"1458","article-title":"Improving precision of vancomycin dosing in neonates based on clinical outcomes and population pharmacokinetics","volume":"12","author":"Chung E","year":"2022","journal-title":"J Am Coll Clin Pharm"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40262-015-0236-8"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jbi.2019.103208"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jbi.2008.08.010"},{"key":"e_1_2_8_15_1","unstructured":"Vitros chemistry products VANC reagent\u2013instructions for use. 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