{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T14:17:59Z","timestamp":1785161879416,"version":"3.55.0"},"reference-count":45,"publisher":"Oxford University Press (OUP)","issue":"8","license":[{"start":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T00:00:00Z","timestamp":1782950400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,7,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>Critically ill infants and children often experience subtherapeutic cefotaxime exposure when administered licenced doses. Dose individualization guided by model informed precision dosing (MIPD) software is emerging, however, external validation of MIPD performance before implementing into clinical practice is necessary. This in silico study assessed the accuracy of an MIPD software in predicting cefotaxime concentrations among critically ill infants and children using the a priori (\u2018empiric\u2019) and the a posteriori (Bayesian forecasting) approaches.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>The study population was between 1\u2005month and 12\u2005years of age receiving cefotaxime in a paediatric intensive care unit. Essential data was inputted into the MIPD software ID-ODSTM to perform the a priori (4\u2005h and 6\u2005h post dose) and the a posteriori (one- and two-measured serum cefotaxime concentrations) predictions. The concentrations predicted by ID-ODS were compared against measured concentrations, using bias, precision and linear regression methods.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Thirty infants and children with 115 concentration measurements produced 194 simulations for analysis. The median age, weight and serum creatinine concentration were 22.8\u2005months, 10.6\u2005kg and 23\u2005\u00b5M\/L, respectively. The a priori approach showed high biases, low precisions, and significant underprediction [weighted mean prediction error (WMPE) \u221248.48%, \u221285.63%, weighted root mean squared prediction error (WRMSE) 98.86, 87.60% at 4\u2005h and 6\u2005h, respectively]. The a posteriori approach exhibited improved accuracy (WMPE 0.28%, \u221221.54%, WRMSE 76.41%, 58.98% for one and two samples, respectively). MIPD-guided dose adjustments achieved pre-defined PK-PD targets in &amp;gt;90% of simulations using the a posteriori approach.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>MIPD incorporating measured blood samples of cefotaxime increases the likelihood of achieved target drug concentrations in treating severe infections among critically ill infants and children.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/jac\/dkag235","type":"journal-article","created":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T13:45:33Z","timestamp":1785159933000},"source":"Crossref","is-referenced-by-count":0,"title":["External validation of a model informed precision dosing software for cefotaxime for treating critical ill infants and children"],"prefix":"10.1093","volume":"81","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1910-1069","authenticated-orcid":false,"given":"Quyen","family":"Tu","sequence":"first","affiliation":[{"name":"Frazer Institute, Faculty of Health, Medicine and Behavioural Sciences, The University of Queensland , Brisbane ,","place":["Australia"]},{"name":"Paediatric Intensive Care Unit, Queensland Children\u2019s Hospital , Brisbane ,","place":["Australia"]},{"name":"Department of Pharmacy, Queensland Children's Hospital , Brisbane ,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sainath","family":"Raman","sequence":"additional","affiliation":[{"name":"Paediatric Intensive Care Unit, Queensland Children\u2019s Hospital , Brisbane ,","place":["Australia"]},{"name":"Children\u2019s Intensive Care Research Program, Child Health Research Centre, Faculty of Medicine, The University of Queensland , Brisbane ,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2058-2314","authenticated-orcid":false,"given":"Menino Osbert","family":"Cotta","sequence":"additional","affiliation":[{"name":"Frazer Institute, Faculty of Health, Medicine and Behavioural Sciences, The University of Queensland , Brisbane ,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luregn","family":"Schlapbach","sequence":"additional","affiliation":[{"name":"Children\u2019s Intensive Care Research Program, Child Health Research Centre, Faculty of Medicine, The University of Queensland , Brisbane ,","place":["Australia"]},{"name":"Department of Pediatric and Neonatal Intensive Care, University Children\u2019s Hospital Zurich , Zurich ,","place":["Switzerland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tavey","family":"Dorofaeff","sequence":"additional","affiliation":[{"name":"Frazer Institute, Faculty 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