{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T03:03:44Z","timestamp":1784862224502,"version":"3.55.0"},"reference-count":30,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2024,3,18]],"date-time":"2024-03-18T00:00:00Z","timestamp":1710720000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["accp1.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Clinical Pharma"],"published-print":{"date-parts":[[2024,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Daptomycin is an antibiotic with Gram\u2010positive activity, including methicillin\u2010resistant <jats:italic>Staphylococcus aureus<\/jats:italic>, for which optimal pediatric dosing is unknown. This study aimed to evaluate daptomycin exposures achieved with package label dosing and to identify dosing regimens necessary to enhance efficacy and minimize toxicity in children with <jats:italic>S. aureus<\/jats:italic> bacteremia. Monte Carlo simulations were performed to determine probability of target attainment (PTA) for six pediatric age cohorts. Area under the curve to minimum inhibitory concentration ratio (AUC<jats:sub>0\u201024<\/jats:sub>:MIC) \u2265666 was used to determine the PTA for efficacy (PTA<jats:sub>E<\/jats:sub>). Minimum concentration (C<jats:sub>min<\/jats:sub>) \u226524.3\u00a0mg\/L determined the PTA for toxicity (PTA<jats:sub>T<\/jats:sub>). Acceptable dosing regimens were those which achieved the combined target of \u226590% PTA<jats:sub>E<\/jats:sub> and \u22645% PTA<jats:sub>T<\/jats:sub>. Package label dosing of daptomycin yielded insufficient efficacy with only 26.3% PTA<jats:sub>E<\/jats:sub> in children 13\u201024 months, 39.5% PTA<jats:sub>E<\/jats:sub> in children 2\u20106 years, 30.1% PTA<jats:sub>E<\/jats:sub> in children 7\u201011 years, and 50.1% PTA<jats:sub>E<\/jats:sub> in adolescents \u226512 years. To achieve the combined efficacy and safety target, doses of 18\u201024\u00a0mg\/kg in children 3\u201012 months, 20\u201024\u00a0mg\/kg in children 13\u201024 months, 19\u201024\u00a0mg\/kg in children 2\u20106 years, 17\u201019\u00a0mg\/kg in children 7\u201011 years, and 10\u201014\u00a0mg\/kg in adolescents \u226512 years are necessary. Package label dosing resulted in suboptimal exposure for the majority of pediatric patients in all age groups evaluated. If targeting validated efficacy and safety endpoints, daily daptomycin doses of at least 20\u00a0mg\/kg in children \u22646 years, 17\u00a0mg\/kg in children 7\u201011 years, and 10\u00a0mg\/kg in adolescents \u226512 years are necessary. Clinical studies evaluating these higher doses are needed.<\/jats:p>","DOI":"10.1002\/jcph.2425","type":"journal-article","created":{"date-parts":[[2024,3,18]],"date-time":"2024-03-18T09:58:38Z","timestamp":1710755918000},"page":"860-865","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Daptomycin Dose Optimization in Pediatric <i>Staphylococcus aureus<\/i> Bacteremia: A Pharmacokinetic\/Pharmacodynamic Investigation"],"prefix":"10.1002","volume":"64","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7536-9070","authenticated-orcid":false,"given":"Katie B.","family":"Olney","sequence":"first","affiliation":[{"name":"Department of Pharmacy Services University of Kentucky HealthCare  Lexington KY USA"},{"name":"Department of Pharmacy Practice and Science University of Kentucky College of Pharmacy  Lexington KY USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joel I.","family":"Howard","sequence":"additional","affiliation":[{"name":"Department of Pediatrics: Division of Infectious Diseases University of Kentucky HealthCare  Lexington KY USA"},{"name":"Department of Pediatrics University of Kentucky College of Medicine  Lexington KY USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David S.","family":"Burgess","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Practice and Science University of Kentucky College of Pharmacy  Lexington KY USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,3,18]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.45.3.845-851.2001"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.48.1.63-68.2004"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00247-06"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.47.4.1318-1323.2003"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10156-013-0559-z"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1086\/647938"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.44.11.2948-2953.2000"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1086\/652767"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12325-015-0267-4"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkt294"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/cit582"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.02967-15"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1177\/1060028021991943"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/phar.2070"},{"key":"e_1_2_8_16_1","unstructured":"Cubicin\u00ae(Daptomycin for Injection). 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