{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,13]],"date-time":"2026-09-13T23:50:22Z","timestamp":1789343422247,"version":"build-2803163510"},"reference-count":134,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T00:00:00Z","timestamp":1781049600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>Aminoglycoside antibiotics remain essential for treating serious neonatal and pediatric infections, yet carry a well-documented risk of permanent auditory and vestibular toxicity. This review examines the pharmacological mechanisms of ototoxicity in pediatric populations, identifies those at highest risk, and assesses current prevention, monitoring, and management strategies.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>PubMed, EMBASE, Cochrane Library, Web of Science, and CINAHL were searched for relevant literature from 2000 to 2025. The primary focus was pediatric populations, though mechanistic and translational pharmacology work from other age groups was included.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>The ototoxicity pathway is increasingly well characterized: aminoglycosides accumulate in cochlear hair cells via mechanoelectrical transduction channels, disrupt mitochondrial function, trigger oxidative stress, and cause cell death through apoptotic, necroptotic, and ferroptotic mechanisms. Susceptibility varies substantially. Patients carrying the MT-RNR1 m.1555A&amp;gt;G pharmacogenomic variant face a markedly elevated risk of profound hearing loss even with a single standard course. Preterm neonates are at higher risk than older children owing to renal immaturity, altered volume of distribution, and incomplete blood-labyrinth barrier development. Co-administration of loop diuretics and vancomycin further amplifies ototoxic risk. Extended-interval dosing is associated with equivalent efficacy and reduced nephrotoxicity, with a non-significant trend toward lower ototoxicity in pooled analyses. Point-of-care genetic screening allows identification of high-risk patients before the first dose, though debate continues over universal versus targeted implementation. Model-informed dosing approaches, including Bayesian forecasting and AUC-targeted monitoring, offer individualized pharmacokinetic optimization but remain underutilized. Antimicrobial stewardship and minimizing concomitant ototoxin exposure are complementary strategies. When ototoxicity occurs, early audiological and vestibular identification enables timely intervention through hearing aid fitting, cochlear implantation, vestibular rehabilitation, and family-centered support, though vestibular ototoxicity remains widely under-recognized in pediatric populations.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Evidence-based interventions to reduce aminoglycoside ototoxicity in children exist, including pharmacogenomic screening and dosing optimization, as well as structured monitoring and rehabilitation. However, a persistent gap remains between available evidence and routine clinical implementation. Key research priorities include pediatric otoprotective trials, validated cochlear injury biomarkers, and implementation strategies for diverse healthcare settings. Given the permanence of aminoglycoside-induced ototoxic injury and its downstream effects on speech, language, and developmental outcomes, closing this gap represents an urgent clinical priority.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fphar.2026.1823729","type":"journal-article","created":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T04:29:12Z","timestamp":1781065752000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Mechanisms, prevention, and management of aminoglycoside-induced hearing loss in neonates and children: a translational review"],"prefix":"10.3389","volume":"17","author":[{"given":"S\u00edlvia M.","family":"Illamola","sequence":"first","affiliation":[{"name":"Department of Experimental and Clinical Pharmacology, College of Pharmacy, University of Minnesota","place":["Minneapolis, MN, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catherine M.","family":"Sherwin","sequence":"additional","affiliation":[{"name":"Department of Experimental and Clinical Pharmacology, College of Pharmacy, University of Minnesota","place":["Minneapolis, MN, United States"]},{"name":"Internal Medicine, UWA Medical School, The University of Western Australia","place":["Perth, WA, Australia"]},{"name":"Differentia Biotech Ltd.","place":["South San Francisco, CA, United States"]},{"name":"Department of Pharmacology and Toxicology, Wright State University Boonshoft School of Medicine","place":["Dayton, OH, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lauren C.","family":"Ferguson","sequence":"additional","affiliation":[{"name":"Department of Emergency Medicine, The University of Texas Southwestern Medical Center","place":["Dallas, TX, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angela K.","family":"Birnbaum","sequence":"additional","affiliation":[{"name":"Department of Experimental and Clinical Pharmacology, College of Pharmacy, University of Minnesota","place":["Minneapolis, MN, United States"]},{"name":"Center for Clinical and Cognitive Neuropharmacology, College of Pharmacy, University of Minnesota","place":["Minneapolis, MN, United States"]},{"name":"Department of Medical Laboratory Sciences, College of Pharmacy, University of Minnesota","place":["Minneapolis, MN, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ravindhra G.","family":"Elluru","sequence":"additional","affiliation":[{"name":"Pediatric Otolaryngology, Peyton Manning Children\u2019s Hospital","place":["Indianapolis, IN, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janelle D.","family":"Vaughns","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Pain and Perioperative Medicine, Children\u2019s National Hospital, GW School of Medicine and Health Sciences, The George Washington University","place":["Washington, DC, United States"]},{"name":"Division of Clinical Pharmacology, Children\u2019s National Hospital, GW School of Medicine and Health Sciences, The George Washington University","place":["Washington, DC, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,6,10]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"86","DOI":"10.5409\/wjcp.v12.i3.86","article-title":"Various aspects of hearing loss in newborns: a narrative review","volume":"12","author":"Al-Ani","year":"2023","journal-title":"World J. 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