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The dose per administration, the dosing interval, the total daily dose, and the demographic characteristics between guidelines were compared. There was considerable variability with respect to dose (4 to 6 mg\/kg), dosing interval (24 h to 48 h), total daily dose (2.5 to 6 mg\/kg\/day), and patient demographic characteristics that were used to calculate individualized dosing regimens. A model-based simulation study in 1071 neonates was performed to determine the achievement of efficacious peak gentamicin concentrations according to predefined MICs (<jats:italic>C<\/jats:italic><jats:sub>max<\/jats:sub>\/MIC \u2265 10) and safe trough concentrations (<jats:italic>C<\/jats:italic><jats:sub>min<\/jats:sub>\u2264 2 mg\/liter) with recommended dosing regimens. MIC targets of 0.5 and 1 mg\/liter were used. Dosing optimization was performed giving priority to the first day of treatment and with the goal of simplifying dosing. Current gentamicin neonatal guidelines allow to achieve effective peak concentrations for MICs \u2264 0.5 mg\/liter but not higher. Model-based simulations indicate that to attain peak gentamicin concentrations of \u226510 mg\/liter, a dose of 7.5 mg\/kg should be administered using an extended dosing interval regimen. Trough concentrations of \u22642 mg\/liter can be maintained with a dosing interval of 36 to 48 h in neonates according to gestational and postnatal age. For treatment beyond 3 days, therapeutic drug monitoring is advised to maintain adequate serum concentrations.<\/jats:p>","DOI":"10.1128\/aac.02004-17","type":"journal-article","created":{"date-parts":[[2018,1,18]],"date-time":"2018-01-18T11:30:51Z","timestamp":1516275051000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":30,"title":["Quantitative Analysis of Gentamicin Exposure in Neonates and Infants Calls into Question Its Current Dosing Recommendations"],"prefix":"10.1128","volume":"62","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4607-3179","authenticated-orcid":false,"given":"Tamara","family":"van Donge","sequence":"first","affiliation":[{"name":"Paediatric Pharmacology and Pharmacometrics Research, University of Basel Children's Hospital, Basel, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marc","family":"Pfister","sequence":"additional","affiliation":[{"name":"Paediatric Pharmacology and Pharmacometrics Research, University of Basel Children's Hospital, Basel, Switzerland"},{"name":"Quantitative Solutions, a Certara Company, London, United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Julia","family":"Bielicki","sequence":"additional","affiliation":[{"name":"Paediatric Pharmacology and Pharmacometrics Research, University of Basel Children's Hospital, Basel, Switzerland"},{"name":"Paediatric Infectious Diseases Research Group, Institute for Infection and Immunity, St George's, University of London, London, United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chantal","family":"Csajka","sequence":"additional","affiliation":[{"name":"Service of Clinical Pharmacology, Department of Laboratory, Centre Hospitalier Universitaire Vaudois and University of Lausanne, Lausanne, Switzerland"},{"name":"School of Pharmaceutical Sciences, University of Geneva, University of Lausanne, Geneva, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Frederique","family":"Rodieux","sequence":"additional","affiliation":[{"name":"Service of Clinical Pharmacology and Toxicology, Geneva University Hospitals, Geneva, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John","family":"van den Anker","sequence":"additional","affiliation":[{"name":"Paediatric Pharmacology and Pharmacometrics Research, University of Basel Children's Hospital, Basel, Switzerland"},{"name":"Intensive Care and Department of Surgery, Erasmus Medical Center-Sophia Children's Hospital, Rotterdam, The Netherlands"},{"name":"Division of Clinical Pharmacology, Children's National Health System, Washington, DC, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aline","family":"Fuchs","sequence":"additional","affiliation":[{"name":"Paediatric Pharmacology and Pharmacometrics Research, University of Basel Children's Hospital, Basel, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(16)31593-8"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1136\/archdischild-2015-309554"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1128\/CMR.00031-13"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.pedneo.2015.09.007"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1097\/INF.0000000000000542"},{"key":"e_1_3_3_7_2","volume-title":"Pocket book of hospital care for children: guidelines for the management of common childhood illnesses","author":"World Health Organization","year":"2013","unstructured":"World Health Organization. 2013. 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