{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T13:20:41Z","timestamp":1753881641288,"version":"3.41.2"},"reference-count":39,"publisher":"American Society for Microbiology","issue":"4","license":[{"start":{"date-parts":[[2025,4,2]],"date-time":"2025-04-02T00:00:00Z","timestamp":1743552000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,4,2]],"date-time":"2025-04-02T00:00:00Z","timestamp":1743552000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"name":"DHAC | National Health and Medical Research Council","award":["1047105"],"award-info":[{"award-number":["1047105"]}]},{"name":"Medical Research Future Fund","award":["1197177"],"award-info":[{"award-number":["1197177"]}]},{"name":"DHAC | National Health and Medical Research Council","award":["1036951"],"award-info":[{"award-number":["1036951"]}]},{"name":"DHAC | National Health and Medical Research Council","award":["1058260"],"award-info":[{"award-number":["1058260"]}]},{"DOI":"10.13039\/501100020265","name":"Stan Perron Charitable Foundation","doi-asserted-by":"crossref","award":["2022\/GR000990"],"award-info":[{"award-number":["2022\/GR000990"]}],"id":[{"id":"10.13039\/501100020265","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[2025,4,2]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:sec>\n            <jats:title\/>\n            <jats:p>Amoxicillin plus gentamicin is the recommended first-line empiric therapy for neonates with infection. Guidelines vary widely in dose (mg\/kg), dose frequency, and adjustments according to post-menstrual age (PMA) and post-natal age (PNA). We aimed to develop a population pharmacokinetic (PK) model for amoxicillin in neonates with clinical evidence of sepsis and design optimal dosing regimens. One hundred seventy-seven neonates receiving intravenous amoxicillin for infection were enrolled in a prospective, observational PK study in Papua New Guinea (PNG). The probability of PK-pharmacodynamic target attainment (PK-PD PTA) was determined based on minimum inhibitory concentrations (MIC) and the proportion of time concentrations that remained above these values (%T &gt; MIC). Neonates with concentrations &gt; 140 mg\/L were considered to be at increased risk of amoxicillin neurotoxicity. A population PK model was developed. Simulations tested existing guidelines and proposed simplified regimens. The median PMA and PNA were 38 (37\u201340) weeks and 0 (0\u20132) days, respectively. From simulations, existing regimens with 50 or 100 mg\/kg doses were associated with higher potential neurotoxic concentrations (24.9% and 84.5%, respectively). With the existing 30 mg\/kg PNG regimen, neonates receiving twice-daily dosing between 3 and 7 days were systematically underdosed. A proposed 30 mg\/kg regimen, with twice-daily dosing for the first 2 days PNA and three times daily from day 3, provides an optimal balance between the probability of PK-PD target attainment while minimizing toxicity. For fixed volume dosing, using 52 mg (0.25 mL of 250 mg in 1.2 mL) for those &lt;3 kg and 104 mg (0.5 mL) for those \u22653 kg is proposed.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1128\/aac.01491-24","type":"journal-article","created":{"date-parts":[[2025,3,4]],"date-time":"2025-03-04T14:00:30Z","timestamp":1741096830000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":0,"title":["A simplified amoxicillin regimen with dose frequency based on post-natal age in neonates with confirmed or suspected infection"],"prefix":"10.1128","volume":"69","author":[{"given":"Mispah","family":"Mukap","sequence":"first","affiliation":[{"name":"School of Medicine, University of Papua New Guinea","place":["Port Moresby, Papua New Guinea"]},{"name":"Papua New Guinea Institute of Medical Research","place":["Goroka, Papua New Guinea"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Corin","family":"Sprod","sequence":"additional","affiliation":[{"name":"School of Medicine, University of Papua New Guinea","place":["Port Moresby, Papua New Guinea"]},{"name":"Papua New Guinea Institute of Medical Research","place":["Goroka, Papua New Guinea"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Okhee","family":"Yoo","sequence":"additional","affiliation":[{"name":"Pharmacy, School of Allied Health, University of Western Australia","place":["Nedlands, Australia"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nakapi","family":"Tefuarani","sequence":"additional","affiliation":[{"name":"School of Medicine, University of Papua New Guinea","place":["Port Moresby, Papua New Guinea"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John","family":"Vince","sequence":"additional","affiliation":[{"name":"School of Medicine, University of Papua New Guinea","place":["Port Moresby, Papua New Guinea"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Moses","family":"Laman","sequence":"additional","affiliation":[{"name":"Papua New Guinea Institute of Medical Research","place":["Goroka, Papua New Guinea"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Madhu","family":"Page-Sharp","sequence":"additional","affiliation":[{"name":"Curtin Medical School, Curtin University","place":["Bentley, Australia"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Brioni R.","family":"Moore","sequence":"additional","affiliation":[{"name":"Curtin Medical School, Curtin University","place":["Bentley, Australia"]},{"name":"Medical School, University of Western Australia, Harry Perkins Research Institute, Fiona Stanley Hospital","place":["Murdoch, Australia"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3850-1778","authenticated-orcid":true,"given":"Kevin T.","family":"Batty","sequence":"additional","affiliation":[{"name":"Curtin Medical School, Curtin University","place":["Bentley, Australia"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0749-7411","authenticated-orcid":true,"given":"Timothy M. 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