{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T22:16:53Z","timestamp":1792707413886,"version":"4.5.0"},"reference-count":68,"publisher":"Oxford University Press (OUP)","issue":"9","license":[{"start":{"date-parts":[[2023,8,2]],"date-time":"2023-08-02T00:00:00Z","timestamp":1690934400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004963","name":"European Union\u2019s Seventh Framework Programme","doi-asserted-by":"publisher","award":["261060"],"award-info":[{"award-number":["261060"]}],"id":[{"id":"10.13039\/501100004963","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000272","name":"National Institute for Health Research","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000272","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Clinical Research Network","award":["UKCRN ID 14960"],"award-info":[{"award-number":["UKCRN ID 14960"]}]},{"DOI":"10.13039\/100006662","name":"NIHR","doi-asserted-by":"publisher","award":["ACF-2016-18-016"],"award-info":[{"award-number":["ACF-2016-18-016"]}],"id":[{"id":"10.13039\/100006662","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006662","name":"NIHR","doi-asserted-by":"publisher","award":["ACF-2019-17-004"],"award-info":[{"award-number":["ACF-2019-17-004"]}],"id":[{"id":"10.13039\/100006662","id-type":"DOI","asserted-by":"publisher"}]},{"name":"NIHR Biomedical Research Centres based at Great Ormond Street Hospital"},{"name":"Guy\u2019s and"},{"name":"St Thomas\u2019 NHS Foundation Trust and King\u2019s College London"},{"name":"C.I.S.B."},{"name":"UK Medical Research Council Fellowships","award":["G1002305"],"award-info":[{"award-number":["G1002305"]}]},{"name":"UK Medical Research Council Fellowships","award":["M008665"],"award-info":[{"award-number":["M008665"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,9,5]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Pharmacokinetic (PK) data underlying paediatric penicillin dosing remain limited, especially in critical care.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Objectives<\/jats:title>\n                  <jats:p>The primary objective of the Neonatal and Paediatric Pharmacokinetics of Antimicrobials study (NAPPA) was to characterize PK profiles of commonly used penicillins using data obtained during routine care, to further understanding of PK variability and inform future evidence-based dosing.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>NAPPA was a multicentre study of amoxicillin, co-amoxiclav, benzylpenicillin, flucloxacillin and piperacillin\/tazobactam. Patients were recruited with informed consent. Antibiotic dosing followed standard of care. PK samples were obtained opportunistically or at optimal times, frozen and analysed using UPLC with tandem MS. Pharmacometric analysis was undertaken using NONMEM software (v7.3). Model-based simulations (n\u200a=\u200a10\u200a000) tested PTA with British National Formulary for Children (BNFC) and WHO dosing. The study had ethical approval.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>For the combined IV PK model, 963 PK samples from 370 participants were analysed simultaneously incorporating amoxicillin, benzylpenicillin, flucloxacillin and piperacillin data. BNFC high-dose regimen simulations gave these PTA results (median fT&amp;gt;MIC at breakpoints of specified pathogens): amoxicillin 100% (Streptococcus pneumoniae); benzylpenicillin 100% (Group B Streptococcus); flucloxacillin 48% (MSSA); and piperacillin 100% (Pseudomonas aeruginosa). Oral population PK models for flucloxacillin and amoxicillin enabled estimation of first-order absorption rate constants (1.16 h\u22121 and 1.3 h\u22121) and bioavailability terms (62.7% and 58.7%, respectively).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>NAPPA represents, to our knowledge, the largest prospective combined paediatric penicillin PK study undertaken to date, and the first paediatric flucloxacillin oral PK model. The PTA results provide evidence supportive of BNFC high-dose IV regimens for amoxicillin, benzylpenicillin and piperacillin.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/jac\/dkad196","type":"journal-article","created":{"date-parts":[[2023,8,2]],"date-time":"2023-08-02T15:09:37Z","timestamp":1690988977000},"page":"2148-2161","source":"Crossref","is-referenced-by-count":16,"title":["The Neonatal and Paediatric Pharmacokinetics of Antimicrobials study (NAPPA): investigating amoxicillin, benzylpenicillin, flucloxacillin and piperacillin pharmacokinetics from birth to adolescence"],"prefix":"10.1093","volume":"78","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6757-5867","authenticated-orcid":false,"given":"Charlotte I S","family":"Barker","sequence":"first","affiliation":[{"name":"Centre for Neonatal and Paediatric Infection, Level 2 Jenner Wing, Institute for Infection and Immunity, St George\u2019s, University of London SW17 0RE , London , UK"},{"name":"Paediatric Infectious Diseases Department, St George\u2019s University Hospitals NHS Foundation Trust , London , UK"},{"name":"Infection, Immunity and Inflammation Research & Teaching Department, UCL Great Ormond Street Institute of Child Health, University College London , London , UK"},{"name":"Department of Medical & Molecular Genetics, King\u2019s College London , London , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7295-8993","authenticated-orcid":false,"given":"Karin","family":"Kipper","sequence":"additional","affiliation":[{"name":"Centre for Neonatal and Paediatric Infection, Level 2 Jenner Wing, Institute for Infection and Immunity, St George\u2019s, University of London SW17 0RE , London , UK"},{"name":"Analytical Services International, St George\u2019s, University of London , London , UK"},{"name":"Analytical Chemistry Department, Epilepsy Society, Chesham Lane, Chalfont St Peter , Buckinghamshire , UK"},{"name":"Institute of Chemistry, University of Tartu , Tartu , Estonia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0838-921X","authenticated-orcid":false,"given":"Dagan O","family":"Lonsdale","sequence":"additional","affiliation":[{"name":"Centre for Neonatal and Paediatric Infection, Level 2 Jenner Wing, Institute for Infection and Immunity, St George\u2019s, University of London SW17 0RE , London , UK"},{"name":"Paediatric Infectious Diseases Department, St George\u2019s University Hospitals NHS Foundation Trust , London , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kirstie","family":"Wright","sequence":"additional","affiliation":[{"name":"Centre for Neonatal and Paediatric Infection, Level 2 Jenner Wing, Institute for Infection and Immunity, St George\u2019s, University of London SW17 0RE , London , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Georgina","family":"Thompson","sequence":"additional","affiliation":[{"name":"Centre for Neonatal and Paediatric Infection, Level 2 Jenner Wing, Institute for Infection and Immunity, St George\u2019s, University of London SW17 0RE , London , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min","family":"Kim","sequence":"additional","affiliation":[{"name":"Centre for Neonatal and Paediatric Infection, Level 2 Jenner Wing, Institute for Infection and Immunity, St George\u2019s, University of London SW17 0RE , London , UK"},{"name":"Infection, Immunity and Inflammation Research & Teaching Department, UCL Great Ormond Street Institute of Child Health, University College London , London , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5299-8656","authenticated-orcid":false,"given":"Mark 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