{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,21]],"date-time":"2026-05-21T14:28:44Z","timestamp":1779373724211,"version":"3.53.1"},"reference-count":38,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2026,1,14]],"date-time":"2026-01-14T00:00:00Z","timestamp":1768348800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Background: Tobramycin is a key therapy for pulmonary exacerbations in children and adolescents with cystic fibrosis (CF), yet its variable pharmacokinetics (PK) combined with narrow therapeutic index necessitates therapeutic drug monitoring (TDM) during clinical care to optimize exposure while minimizing toxicity. Model-informed precision dosing (MIPD) is a potentially powerful tool to support dose individualization in clinical care that leverages population PK models and Bayesian forecasting. Herein, we evaluated the performance of an MIPD initiative at our hospital for once-daily tobramycin in pediatric patients with CF. Methods: Tobramycin practices at a single CF center before (2016\u20132018) and after (2019\u20132025) implementation of an MIPD initiative in CF patients &lt; 21 years were evaluated. TDM during the pre-MIPD period used traditional log-linear AUC calculations, while the post-MIPD period used a commercial MIPD software platform integrated within the electronic health record. Outcomes included attainment of the target 24 h area-under-the-curve (AUC24 80\u2013120 mg\u00b7h\/L), number of TDM samples and dose adjustments during the first 7 days of treatment, and rates of acute kidney injury (AKI). Results: A total of 114 treatment courses were analyzed (77 pre-MIPD, 37 post-MIPD). Post-MIPD target attainment was 75.7% at TDM1, 89.2% at TDM2, and 100% at TDM3, significantly higher than pre-MIPD at corresponding cycles. The post-MIPD period required fewer TDM samples (4.2 vs. 7.1; p &lt; 0.001) and dose adjustments (0.7 vs. 1.8; p &lt; 0.001) in the first 7 days. AKI incidence remained low and comparable between periods. Conclusions: Implementation of an MIPD initiative for tobramycin in pediatric patients with CF led to the early attainment of therapeutic AUC24 targets while reducing TDM burden and dose adjustments.<\/jats:p>","DOI":"10.3390\/ph19010150","type":"journal-article","created":{"date-parts":[[2026,1,14]],"date-time":"2026-01-14T15:47:37Z","timestamp":1768405657000},"page":"150","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Hitting the Target: Model-Informed Precision Dosing of Tobramycin in Pediatric Patients with Cystic Fibrosis"],"prefix":"10.3390","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8018-5839","authenticated-orcid":false,"given":"Jake M.","family":"Brockmeyer","sequence":"first","affiliation":[{"name":"Department of Pharmacy, Lucile Packard Children\u2019s Hospital Stanford, Palo Alto, CA 94304, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9520-6420","authenticated-orcid":false,"given":"Laura","family":"Bio","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Lucile Packard Children\u2019s Hospital Stanford, Palo Alto, CA 94304, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5515-3053","authenticated-orcid":false,"given":"Carlos","family":"Milla","sequence":"additional","affiliation":[{"name":"Division of Pediatric Pulmonary Medicine, Stanford University, Stanford, CA 94305, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1095-9381","authenticated-orcid":false,"given":"Adam","family":"Frymoyer","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Stanford University, Stanford, CA 94305, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,1,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"802","DOI":"10.1164\/rccm.200812-1845PP","article-title":"Clinical Practice Guidelines for Pulmonary Therapies Committee. Cystic Fibrosis Pulmonary Guidelines: Treatment of Pulmonary Exacerbations","volume":"180","author":"Flume","year":"2009","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"573","DOI":"10.1016\/S0140-6736(05)17906-9","article-title":"Once versus three-times daily regimens of tobramycin treatment for pulmonary exacerbations of cystic fibrosis--the TOPIC study: A randomised controlled trial","volume":"365","author":"Smyth","year":"2005","journal-title":"Lancet"},{"key":"ref_3","first-page":"CD002009","article-title":"Once-daily versus multiple-daily dosing with intravenous aminoglycosides for cystic fibrosis","volume":"9","author":"Bhatt","year":"2019","journal-title":"Cochrane Database Syst. Rev."},{"key":"ref_4","first-page":"152","article-title":"Safety of Extended Interval Tobramycin in Cystic Fibrosis Patients Less Than 6 Years Old","volume":"23","author":"Arends","year":"2018","journal-title":"J. Pediatr. Pharmacol. Ther."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"e0237721","DOI":"10.1128\/aac.02377-21","article-title":"A Pharmacokinetic Analysis of Tobramycin in Patients Less than Five Years of Age with Cystic Fibrosis: Assessment of Target Attainment with Extended-Interval Dosing through Simulation","volume":"66","author":"Downes","year":"2022","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_6","first-page":"63","article-title":"Review of Tobramycin Dosing in Pediatric Patients With Cystic Fibrosis","volume":"28","author":"Imburgia","year":"2023","journal-title":"J. Pediatr. Pharmacol. Ther. JPPT Off. J. PPAG"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"e0027825","DOI":"10.1128\/aac.00278-25","article-title":"Personalized tobramycin dosing in children with cystic fibrosis: An AUC24-guided approach","volume":"69","author":"Harwood","year":"2025","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1007\/s40262-013-0036-y","article-title":"Population Pharmacokinetics of Tobramycin in Patients With and Without Cystic Fibrosis","volume":"52","author":"Hennig","year":"2013","journal-title":"Clin. Pharmacokinet."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1016\/j.diagmicrobio.2005.02.011","article-title":"Pharmacodynamics of tobramycin in patients with cystic fibrosis","volume":"52","author":"Mouton","year":"2005","journal-title":"Diagn. Microbiol. Infect. Dis."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"822","DOI":"10.1093\/jac\/dkl328","article-title":"Once-daily tobramycin in cystic fibrosis: Better for clinical outcome than thrice-daily tobramycin but more resistance development?","volume":"58","author":"Burkhardt","year":"2006","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"400","DOI":"10.1016\/j.clinthera.2023.03.015","article-title":"Population Pharmacokinetics and AUC-Guided Dosing of Tobramycin in the Treatment of Infections Caused by Glucose-Nonfermenting Gram-Negative Bacteria","volume":"45","author":"Hashiguchi","year":"2023","journal-title":"Clin. Ther."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1002\/jppr.1145","article-title":"Usage and monitoring of intravenous tobramycin in cystic fibrosis in Australia and the UK","volume":"46","author":"Paviour","year":"2016","journal-title":"J. Pharm. Pr. Res."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"2528","DOI":"10.1128\/AAC.01314-10","article-title":"Optimization of aminoglycoside therapy","volume":"55","author":"Drusano","year":"2011","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1016\/j.addr.2014.05.016","article-title":"Innovative approaches to optimizing the delivery of vancomycin in individual patients","volume":"77","author":"Pai","year":"2014","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"3343","DOI":"10.1002\/ppul.25037","article-title":"Area under the curve achievement of once daily tobramycin in children with cystic fibrosis during clinical care","volume":"55","author":"Brockmeyer","year":"2020","journal-title":"Pediatr. Pulmonol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1002\/cpt.1679","article-title":"Development and Implementation of Electronic Health Record-Integrated Model-Informed Clinical Decision Support Tools for the Precision Dosing of Drugs","volume":"107","author":"Vinks","year":"2019","journal-title":"Clin. Pharmacol. Ther."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1146\/annurev-pharmtox-033020-113257","article-title":"Model-Informed Precision Dosing: Background, Requirements, Validation, Implementation, and Forward Trajectory of Individualizing Drug Therapy","volume":"61","author":"Darwich","year":"2021","journal-title":"Annu. Rev. Pharmacol. Toxicol."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Frymoyer, A., Schwenk, H.T., Zorn, Y., Bio, L., Moss, J.D., Chasmawala, B., Faulkenberry, J., Goswami, S., Keizer, R.J., and Ghaskari, S. (2020). Model-Informed Precision Dosing of Vancomycin in Hospitalized Children: Implementation and Adoption at an Academic Children\u2019s Hospital. Front. Pharmacol., 11.","DOI":"10.3389\/fphar.2020.00551"},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Del Valle-Moreno, P., Suarez-Casillas, P., Mej\u00edas-Trueba, M., Ciudad-Guti\u00e9rrez, P., Guisado-Gil, A.B., Gil-Navarro, M.V., and Herrera-Hidalgo, L. (2023). Model-Informed Precision Dosing Software Tools for Dosage Regimen Individualization: A Scoping Review. Pharmaceutics, 15.","DOI":"10.3390\/pharmaceutics15071859"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1007","DOI":"10.1002\/phar.2845","article-title":"Impact of model-informed precision dosing on achievement of vancomycin exposure targets in pediatric patients with cystic fibrosis","volume":"432","author":"Frymoyer","year":"2023","journal-title":"Pharmacotherapy"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1295","DOI":"10.1164\/rccm.202102-0461OC","article-title":"A Randomized Clinical Trial of Antimicrobial Duration for Cystic Fibrosis Pulmonary Exacerbation Treatment","volume":"204","author":"Goss","year":"2021","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1093\/ajhp\/zxaf142","article-title":"Implementation of the VancomycIn per Pharmacy Education tRaining (VIPER) program for pharmacists at a children\u2019s hospital","volume":"83","author":"Bio","year":"2026","journal-title":"Am. J. Health Syst. Pharm."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"677","DOI":"10.1093\/jac\/39.6.677","article-title":"Once-daily dosing of aminoglycosides: Review and recommendations for clinical practice","volume":"39","author":"Freeman","year":"1997","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1016\/S0022-3476(84)80375-3","article-title":"Disposition of tobramycin in patients with cystic fibrosis: A prospective controlled study","volume":"105","author":"Levy","year":"1984","journal-title":"J. Pediatr."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"951","DOI":"10.1002\/psp4.12832","article-title":"Altered intravenous drug disposition in people living with cystic fibrosis: A meta-analysis integrating top-down and bottom-up data","volume":"11","author":"Vermeulen","year":"2022","journal-title":"CPT Pharmacomet. Syst. Pharmacol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"106381","DOI":"10.1016\/j.ijantimicag.2021.106381","article-title":"Pharmacokinetics and pharmacodynamics of antibiotics in cystic fibrosis: A narrative review","volume":"58","author":"Castagnola","year":"2021","journal-title":"Int. J. Antimicrob. Agents"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"809","DOI":"10.1128\/AAC.44.4.809-813.2000","article-title":"Pharmacokinetics of tobramycin in adults with cystic fibrosis: Implications for once-daily administration","volume":"44","author":"Beringer","year":"2000","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_28","first-page":"655","article-title":"Impact of Patient-Specific Aminoglycoside Monitoring for Treatment of Pediatric Cystic Fibrosis Pulmonary Exacerbations","volume":"27","author":"Hemmann","year":"2022","journal-title":"J. Pediatr. Pharmacol. Ther. JPPT"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1879","DOI":"10.1007\/s00467-015-3097-3","article-title":"Risk factors for acute kidney injury during aminoglycoside therapy in patients with cystic fibrosis","volume":"30","author":"Downes","year":"2015","journal-title":"Pediatr. Nephrol."},{"key":"ref_30","first-page":"379","article-title":"Use of the NINJA (Nephrotoxic Injury Negated by Just-in-Time Action) Program to Identify Nephrotoxicity in Pediatric Patients with Cystic Fibrosis","volume":"26","author":"Newton","year":"2021","journal-title":"J. Pediatr. Pharmacol. Ther. JPPT"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"819","DOI":"10.1164\/rccm.200109-012CC","article-title":"Aminoglycoside Prescribing and Surveillance in Cystic Fibrosis","volume":"167","author":"Tan","year":"2003","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"3384","DOI":"10.1002\/ppul.25066","article-title":"Incidence of nephrotoxicity with prolonged aminoglycoside exposure in patients with cystic fibrosis","volume":"55","author":"Saad","year":"2020","journal-title":"Pediatr. Pulmonol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"633","DOI":"10.1002\/cpt.3510","article-title":"Barriers and Facilitators for Bringing Model-Informed Precision Dosing to the Patient\u2019s Bedside: A Systematic Review","volume":"117","author":"Dibbets","year":"2024","journal-title":"Clin. Pharmacol. Ther."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"857","DOI":"10.1093\/jac\/dkaf011","article-title":"Therapeutic drug monitoring versus Bayesian AUC-based dosing for vancomycin in routine practice: A cost\u2013benefit analysis","volume":"80","author":"Claus","year":"2025","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1346.e1","DOI":"10.1016\/j.cmi.2020.11.008","article-title":"Cost\u2013benefit analysis comparing trough, two-level AUC and Bayesian AUC dosing for vancomycin","volume":"27","author":"Lee","year":"2021","journal-title":"Clin. Microbiol. Infect."},{"key":"ref_36","first-page":"239","article-title":"Tobramycin and Beta-Lactam Antibiotic Use in Cystic Fibrosis Exacerbations: A Pharmacist Approach","volume":"21","author":"Zobell","year":"2016","journal-title":"J. Pediatr. Pharmacol. Ther. JPPT"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"389","DOI":"10.1007\/s40262-018-0707-9","article-title":"Monitoring of Tobramycin Exposure: What is the Best Estimation Method and Sampling Time for Clinical Practice?","volume":"58","author":"Gao","year":"2019","journal-title":"Clin. Pharmacokinet."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"6698","DOI":"10.1128\/AAC.01131-16","article-title":"Bayesian Estimation of Tobramycin Exposure in Patients with Cystic Fibrosis","volume":"60","author":"Barras","year":"2016","journal-title":"Antimicrob. Agents Chemother."}],"container-title":["Pharmaceuticals"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1424-8247\/19\/1\/150\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,14]],"date-time":"2026-01-14T15:48:17Z","timestamp":1768405697000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1424-8247\/19\/1\/150"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1,14]]},"references-count":38,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,1]]}},"alternative-id":["ph19010150"],"URL":"https:\/\/doi.org\/10.3390\/ph19010150","relation":{},"ISSN":["1424-8247"],"issn-type":[{"value":"1424-8247","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1,14]]}}}