{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T12:28:54Z","timestamp":1785414534571,"version":"3.56.0"},"reference-count":33,"publisher":"American Society for Microbiology","issue":"6","license":[{"start":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T00:00:00Z","timestamp":1780444800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T00:00:00Z","timestamp":1780444800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"name":"Pediatric Subspecialty Faculty at Children\u2019s Hospital of Orange County","award":["2008060-16975008"],"award-info":[{"award-number":["2008060-16975008"]}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[2026,6,3]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title\/>\n                    <jats:p>\n                      <jats:italic toggle=\"yes\">Staphylococcus aureus<\/jats:italic>\n                      increasingly causes late-onset neonatal sepsis with mortality \u226425%. Oxacillin treats methicillin-susceptible\n                      <jats:italic toggle=\"yes\">Staphylococcus aureus<\/jats:italic>\n                      (MSSA). No previous studies inform dosing. Time above MIC of unbound oxacillin (\n                      <jats:italic toggle=\"yes\">f<\/jats:italic>\n                      T&gt;MIC) 100% of dosing interval is a desired pharmacodynamic (PD) target in immunocompromised\/septic patients. Our objective was to characterize oxacillin pharmacokinetics (PK) and PD in young infants. We conducted a prospective PK\/PD study in infants \u226490 days. We divided four cohorts per gestational (GA &lt;32\/\u226532 weeks) and postnatal age (PNA &lt;14\/\u226514 days). Patients received 25 mg\/kg loading doses followed by continuous infusions of 120 (&lt;32 weeks\/&lt;14 days) or 160 mg\/kg\/day. Population PK parameters were estimated using NONMEM. Dosing regimens were evaluated using Monte Carlo simulations to estimate the probability of PD target attainment. Outcomes were collected. We enrolled 22 infants, median (IQR) GA 38 weeks (30\u201339) and PNA 32 days (12\u201346). PNA and weight were covariates for oxacillin clearance. Unbound steady-state oxacillin concentrations remained &gt;MIC 0.5 throughout the dosing interval for &gt;90% of modeled patients for all age groups on 160 mg\/kg\/day continuous infusions. Infants with PNA \u226428 days met PD targets at MIC 1; &lt;90% of all modeled patients on continuous infusion met PD targets at MIC 2. Modeled infants receiving 200 mg\/kg\/day oxacillin divided q4h\/q6h failed to meet PD targets up to MIC 2. All patients survived to discharge. A few serious adverse events were noted. 160 mg\/kg\/day continuous oxacillin was well tolerated and achieved PD targets for MIC \u22640.5 across all age groups. Modeled intermittent dosing \u2264200 mg\/kg\/day divided q4h\/q6h, 8 times the Food and Drug Administration-labeled dose of 25 mg\/kg daily, failed to achieve PD targets. The FDA-recommended oxacillin dose is inadequate and may help explain high mortality.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1128\/aac.01777-25","type":"journal-article","created":{"date-parts":[[2026,4,20]],"date-time":"2026-04-20T18:33:41Z","timestamp":1776710021000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":0,"title":["Population pharmacokinetics and safety of continuous oxacillin in preterm and term neonates and infants"],"prefix":"10.1128","volume":"70","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2426-8151","authenticated-orcid":true,"given":"Adam","family":"Lee","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/0282qcz50","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Infectious Diseases, Children's Hospital of Orange County","place":["Orange, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catherine","family":"Liu","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/0168r3w48","id-type":"ROR","asserted-by":"publisher"}],"name":"Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California-San Diego","place":["La Jolla, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. Tuan","family":"Tran","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/0282qcz50","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Pharmacy, Children's Hospital of Orange County","place":["Orange, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suna","family":"Phal","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/0282qcz50","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Infectious Diseases, Children's Hospital of Orange County","place":["Orange, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charles A.","family":"Peloquin","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02y3ad647","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Translational Research, Infectious Disease Pharmacokinetic Laboratory, University of Florida","place":["Gainesville, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Delma","family":"Nieves","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/0282qcz50","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Infectious Diseases, Children's Hospital of Orange County","place":["Orange, USA"]},{"id":[{"id":"https:\/\/ror.org\/04gyf1771","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Pediatrics, University of California-Irvine","place":["Irvine, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1630-0505","authenticated-orcid":true,"given":"Edmund","family":"Capparelli","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/0168r3w48","id-type":"ROR","asserted-by":"publisher"}],"name":"Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California-San Diego","place":["La Jolla, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9281-8915","authenticated-orcid":false,"given":"Antonio C.","family":"Arrieta","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/0282qcz50","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Infectious Diseases, Children's Hospital of Orange County","place":["Orange, USA"]},{"id":[{"id":"https:\/\/ror.org\/04gyf1771","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Pediatrics, University of California-Irvine","place":["Irvine, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1542\/peds.2022-058813"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1542\/peds.2011-0966"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1097\/INF.0000000000001570"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1001\/jamapediatrics.2025.0429"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.iccn.2023.103421"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.1097\/INF.0b013e318224546d"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41372-022-01440-3"},{"key":"e_1_3_4_9_2","doi-asserted-by":"publisher","DOI":"10.1136\/adc.2002.009480"},{"key":"e_1_3_4_10_2","doi-asserted-by":"publisher","DOI":"10.3390\/antibiotics11121736"},{"key":"e_1_3_4_11_2","doi-asserted-by":"publisher","DOI":"10.1345\/aph.1E271"},{"key":"e_1_3_4_12_2","doi-asserted-by":"publisher","DOI":"10.5863\/1551-6776-22.4.276"},{"key":"e_1_3_4_13_2","doi-asserted-by":"publisher","DOI":"10.1007\/s40262-023-01230-w"},{"key":"e_1_3_4_14_2","unstructured":"Baxter Healthcare Corporation. 2015. U.S. federal drug administration website. Available from: https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/2015\/050640s017lbl.pdf"},{"key":"e_1_3_4_15_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIR.0000000000000298"},{"key":"e_1_3_4_16_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.02624-14"},{"key":"e_1_3_4_17_2","doi-asserted-by":"publisher","DOI":"10.1097\/INF.0b013e31822e8b0b"},{"key":"e_1_3_4_18_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00467-020-04749-3"},{"key":"e_1_3_4_19_2","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/ciw861"},{"key":"e_1_3_4_20_2","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/ciu296"},{"key":"e_1_3_4_21_2","doi-asserted-by":"publisher","DOI":"10.1093\/jpids\/piab027"},{"key":"e_1_3_4_22_2","doi-asserted-by":"publisher","DOI":"10.1542\/peds.39.1.97"},{"key":"e_1_3_4_23_2","unstructured":"Oxacillin. Pediatric and Neonatal Lexi-Drugs. 2023. Lexicomp. Lexicomp Online. 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