{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T16:54:07Z","timestamp":1792688047876,"version":"4.5.0"},"reference-count":42,"publisher":"American Society for Microbiology","issue":"9","license":[{"start":{"date-parts":[[2025,9,3]],"date-time":"2025-09-03T00:00:00Z","timestamp":1756857600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,9,3]],"date-time":"2025-09-03T00:00:00Z","timestamp":1756857600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[2025,9,3]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title\/>\n                    <jats:p>\n                      Tobramycin is commonly used for the treatment of pulmonary exacerbations in children with cystic fibrosis (CF). Currently, a standard dose of 10 mg\/kg daily is used in all children. We aim to develop a population pharmacokinetic (popPK) model of tobramycin in children with CF and determine the: (i) effect of cystic fibrosis transmembrane conductance regulator (CFTR) modulators on tobramycin pharmacokinetics (PK); (ii) attainment of the commonly used serum steady state area under the concentration-time curve target (AUC\n                      <jats:sub>24,ss<\/jats:sub>\n                      ) of 80\u2013110 mg\/L\u22c5h with standard dosing; and (iii) generate an optimized fully individualized dosing strategy to improve target attainment. Multicenter prospective observational study of children with CF aged 0\u201319 years receiving IV tobramycin who had \u22651 serum concentration measured. A popPK model was developed using nonlinear mixed-effect modeling, and simulations were performed to assess study aims. Overall, 63 children had 450 serum tobramycin concentrations. A one-compartment popPK model, including age, weight, a renal maturation model, and estimated glomerular filtration rate as covariates, was developed. With standard dosing, 1\/3 of children achieved the target AUC\n                      <jats:sub>24,ss<\/jats:sub>\n                      with younger children (&lt;2 years) having the lowest probability of target attainment (PTA) (15%). The optimized dosing regimen improved target attainment in all children, increasing the PTA in children &lt;2 years to 62%. CFTR modulator drugs did not affect tobramycin PK. Standard tobramycin dosing in children with CF achieves poor attainment of target serum AUC\n                      <jats:sub>24,ss<\/jats:sub>\n                      , particularly in children &lt;2 years. A fully individualized approach (available at\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"https:\/\/www.kidscalc.org\/\" xlink:type=\"simple\">https:\/\/www.kidscalc.org\/<\/jats:ext-link>\n                      ) improved target attainment in all children. CFTR modulators had a negligible effect on tobramycin PK.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1128\/aac.00278-25","type":"journal-article","created":{"date-parts":[[2025,7,23]],"date-time":"2025-07-23T12:00:50Z","timestamp":1753272050000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":5,"title":["Personalized tobramycin dosing in children with cystic fibrosis: an AUC\n                    <sub>24<\/sub>\n                    -guided approach"],"prefix":"10.1128","volume":"69","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-9507-2497","authenticated-orcid":true,"given":"Kiera H.","family":"Harwood","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/01ej9dk98","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Paediatrics, The University of Melbourne","place":["Parkville, 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