{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,9,11]],"date-time":"2025-09-11T21:54:45Z","timestamp":1757627685527,"version":"3.44.0"},"reference-count":21,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,9,10]],"date-time":"2025-09-10T00:00:00Z","timestamp":1757462400000},"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><jats:title>Purpose<\/jats:title><jats:p>To investigate the safety of off-label high-dose vancomycin use in severely ill children and explore strategies to control risks.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>A case of acute kidney injury caused by off-label high-dose vancomycin (exceeding 40\u00a0mg\/kg\/day) in the Pediatric Intensive Care Unit (PICU) was analyzed. A retrospective case-control review of vancomycin treatment in 39 PICU patients from January to June 2020 were conducted.<\/jats:p><\/jats:sec><jats:sec><jats:title>Findings<\/jats:title><jats:p>Among the 39 patients, 20 (51.3%) received off-label high-dose vancomycin dosing, and only 53.8% (21\/39) underwent blood concentration testing. Five patients (25%; 5\/20) in the off-label use group experienced vancomycin-associated adverse reactions, including three cases of severe ones. Based on risk factor analysis, we implemented improvement measures such as increasing the monitoring of vancomycin trough serum concentration, providing individualized drug regimens, enhancing training, and formally documenting off-label drug use. After implementing these measures from July 2020 to December 2022, a total of 86 children in the PICU were treated with vancomycin, and no cases of vancomycin-associated acute kidney injury was observed. The monitoring rate of vancomycin blood concentration increased to 88.4% (76\/86).<\/jats:p><\/jats:sec><jats:sec><jats:title>Implications<\/jats:title><jats:p>There is a risk of renal function damage when using high dosage of vancomycin in severely ill children, and healthcare providers should pay special attention to this in clinical medication safety practices.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fphar.2025.1680239","type":"journal-article","created":{"date-parts":[[2025,9,10]],"date-time":"2025-09-10T04:17:17Z","timestamp":1757477837000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Pharmacovigilance practice on off-label high-dose of vancomycin in severely ill children"],"prefix":"10.3389","volume":"16","author":[{"given":"Min","family":"Qin","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wenwen","family":"Chen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bin","family":"Lu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yi","family":"Deng","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2025,9,10]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"31","DOI":"10.1007\/s13318-021-00730-z","article-title":"Pharmacokinetics of vancomycin in critically ill children: a systematic review","volume":"47","author":"Akunne","year":"2022","journal-title":"Eur. J. Drug Metab. Pharmacokinet."},{"key":"B2","doi-asserted-by":"publisher","first-page":"650","DOI":"10.3760\/cma.j.issn.0578-1310.2015.09.005","article-title":"Expert consensus on therapeutic drug monitoring for children","volume":"53","year":"2015","journal-title":"Chin. J. Pediatr."},{"key":"B3","doi-asserted-by":"publisher","first-page":"8","DOI":"10.1592\/phco.23.5.643.32199","article-title":"Mississippi mud no more: cost effectiveness of pharmacokinetic dosage adjustment of vancomycin to prevent nephrotoxicity","volume":"23","author":"Darko","year":"2003","journal-title":"Pharmacotherapy"},{"key":"B4","doi-asserted-by":"publisher","first-page":"3162","DOI":"10.1200\/JCO.18.00407","article-title":"Guideline for the management of Clostridium difficile infection in children and adolescents with cancer and pediatric hematopoietic stem-cell transplantation recipients","volume":"36","author":"Diorio","year":"2018","journal-title":"J. Clin. Oncol."},{"key":"B5","doi-asserted-by":"publisher","first-page":"e173219","DOI":"10.1001\/jamapediatrics.2017.3219","article-title":"Association of acute kidney injury with concomitant vancomycin and piperacillin\/tazobactam treatment among hospitalized children","volume":"171","author":"Downes","year":"2017","journal-title":"JAMA Pediatr."},{"key":"B6","doi-asserted-by":"publisher","first-page":"1243","DOI":"10.1007\/s00228-012-1259-9","article-title":"Vancomycin-induced nephrotoxicity: mechanism, incidence, risk factors and special populations. A literature review","volume":"68","author":"Elyasi","year":"2012","journal-title":"Eur. J. Clin. Pharmacol."},{"key":"B7","doi-asserted-by":"publisher","first-page":"151","DOI":"10.1016\/j.ijid.2019.12.036","article-title":"Correlation of the vancomycin 24-h area under the concentration-time curve (AUC24) and trough serum concentration in children with severe infection: a clinical pharmacokinetic study","volume":"92","author":"Issaranggoon Na Ayuthaya","year":"2020","journal-title":"Int. J. Infect. Dis."},{"key":"B8","doi-asserted-by":"publisher","first-page":"1309","DOI":"10.1056\/NEJMoa1914433","article-title":"Multidrug-resistant bacterial infections in U.S. Hospitalized patients, 2012-2017","volume":"382","author":"Jernigan","year":"2020","journal-title":"N. Engl. J. Med."},{"key":"B9","doi-asserted-by":"publisher","first-page":"179","DOI":"10.1016\/j.ijantimicag.2013.10.017","article-title":"Area under the concentration-time curve to minimum inhibitory concentration ratio as a predictor of vancomycin treatment outcome in methicillin-resistant Staphylococcus aureus bacteraemia","volume":"43","author":"Jung","year":"2014","journal-title":"Int. J. Antimicrob. Agents"},{"key":"B10","doi-asserted-by":"publisher","first-page":"e00067-19","DOI":"10.1128\/AAC.00067-19","article-title":"Revising pediatric vancomycin dosing accounting for nephrotoxicity in a pharmacokinetic-pharmacodynamic model","volume":"63","author":"Kloprogge","year":"2019","journal-title":"Antimicrob. Agents Chemother."},{"key":"B11","doi-asserted-by":"publisher","first-page":"e18","DOI":"10.1093\/cid\/ciq146","article-title":"Clinical practice guidelines by the infectious diseases society of America for the treatment of methicillin-resistant Staphylococcus aureus infections in adults and children","volume":"52","author":"Liu","year":"2011","journal-title":"Clin. Infect. Dis."},{"key":"B12","doi-asserted-by":"publisher","first-page":"327","DOI":"10.1007\/s40262-014-0134-5","article-title":"Dosing in children: a critical review of the pharmacokinetic allometric scaling and modelling approaches in paediatric drug development and clinical settings","volume":"53","author":"Mahmood","year":"2014","journal-title":"Clin. Pharmacokinet."},{"key":"B13","doi-asserted-by":"publisher","first-page":"3077","DOI":"10.1111\/apa.16025","article-title":"Children may need higher vancomycin doses to achieve therapeutic levels","volume":"110","author":"Oskarsdottir","year":"2021","journal-title":"Acta Paediatr."},{"key":"B14","doi-asserted-by":"publisher","first-page":"835","DOI":"10.1093\/ajhp\/zxaa036","article-title":"Therapeutic monitoring of vancomycin for serious methicillin-resistant staphylococcus aureus infections: a revised consensus guideline and review by the American society of health-system pharmacists, the infectious diseases society of America, the pediatric infectious diseases society, and the society of infectious diseases pharmacists","volume":"77","author":"Rybak","year":"2020","journal-title":"Am. J. Health Syst. Pharm."},{"key":"B15","first-page":"1","article-title":"Vancomycin","volume-title":"xPharm: the comprehensive Pharmacology reference","author":"Scholar","year":"2007"},{"key":"B16","doi-asserted-by":"publisher","first-page":"53","DOI":"10.1208\/s12248-021-00577-x","article-title":"Dosing recommendations for vancomycin in children and adolescents with varying levels of obesity and renal dysfunction: a population pharmacokinetic study in 1892 children aged 1-18 years","volume":"23","author":"Smit","year":"2021","journal-title":"AAPS J."},{"key":"B17","doi-asserted-by":"publisher","first-page":"2591","DOI":"10.1111\/bcp.14084","article-title":"Vancomycin is commonly under-dosed in critically ill children and neonates","volume":"85","author":"Sosnin","year":"2019","journal-title":"Br. J. Clin. Pharmacol."},{"key":"B18","doi-asserted-by":"publisher","first-page":"807","DOI":"10.1007\/s13318-019-00568-6","article-title":"Clinical pharmacokinetics of vancomycin in critically ill children","volume":"44","author":"Sridharan","year":"2019","journal-title":"Eur. J. Drug Metab. Pharmacokinet."},{"key":"B19","doi-asserted-by":"publisher","first-page":"7","DOI":"10.1007\/s11095-016-2033-y","article-title":"Clinical Pharmacology studies in critically ill children","volume":"34","author":"Thakkar","year":"2017","journal-title":"Pharm. Res."},{"key":"B20","doi-asserted-by":"publisher","first-page":"10","DOI":"10.3760\/cma.j.issn.1008-5734.2017.01.004","article-title":"Initial development of a high-alert medication list for children in China","volume":"19","author":"Wang","year":"2017","journal-title":"Adverse Drug React. J."},{"key":"B21","doi-asserted-by":"publisher","first-page":"1299","DOI":"10.1007\/s00467-020-04820-z","article-title":"Baseline kidney function is associated with vancomycin-induced acute kidney injury in children: a prospective nested case-control study","volume":"36","author":"Zhang","year":"2021","journal-title":"Pediatr. Nephrol."}],"container-title":["Frontiers in Pharmacology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2025.1680239\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,9,10]],"date-time":"2025-09-10T04:17:18Z","timestamp":1757477838000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2025.1680239\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,9,10]]},"references-count":21,"alternative-id":["10.3389\/fphar.2025.1680239"],"URL":"https:\/\/doi.org\/10.3389\/fphar.2025.1680239","relation":{},"ISSN":["1663-9812"],"issn-type":[{"value":"1663-9812","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,9,10]]},"article-number":"1680239"}}