{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,30]],"date-time":"2025-12-30T17:53:18Z","timestamp":1767117198844,"version":"3.41.2"},"reference-count":29,"publisher":"American Society for Microbiology","issue":"11","license":[{"start":{"date-parts":[[2024,11,6]],"date-time":"2024-11-06T00:00:00Z","timestamp":1730851200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/doi.org\/10.1128\/ASMCopyrightv2"},{"start":{"date-parts":[[2024,11,6]],"date-time":"2024-11-06T00:00:00Z","timestamp":1730851200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[2024,11,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:sec>\n            <jats:title\/>\n            <jats:p>\n              Guidelines for bacterial meningitis in children recommend intravenous ceftriaxone 50 mg\/kg (max 2 g) twice daily (BD) or 100 mg\/kg (max 4 g) once daily (OD), leaving the decision regarding the dose frequency to the prescriber. We investigated the cerebrospinal fluid (CSF) penetration of ceftriaxone to evaluate whether one dosing regimen is superior. Unbound ceftriaxone concentrations were measured in serum and CSF samples from children aged 0\u201318 years treated with ceftriaxone if there was a sample remaining after clinical tests were performed. A serum\u2013CSF population pharmacokinetic model was developed using non-linear mixed-effects modeling. The once- and twice-daily dosing regimens were simulated, and the probability of target attainment (PTA) was determined for maintaining a CSF concentration above a minimum inhibitory concentration (MIC) of 1 mg\/L for common meningitis pathogens and 4 mg\/L for\n              <jats:italic>Staphylococcus aureus<\/jats:italic>\n              for 100% of the dosing interval. Sixteen serum and 87 CSF samples were collected from 98 children (age range 0.1\u201318.5 years). The final two-compartment serum\u2013CSF model included a renal maturation function with weight scaling on clearance and volume of distribution. The estimated serum:CSF uptake was 20.1%. For MIC 1 mg\/L, the 24 h PTA was higher for OD (88%) compared with BD (53%) dosing, although both achieved a 100% PTA at steady state. For\n              <jats:italic>S. aureus<\/jats:italic>\n              (MIC 4 mg\/L), neither dosing regimen was sufficient. Our findings support the use of a 100 mg\/kg once daily regimen for empirical treatment of bacterial meningitis due to earlier achievement of the pharmacodynamic target. Neither dosing regimen was adequate for\n              <jats:italic>S. aureus<\/jats:italic>\n              meningitis.\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1128\/aac.00747-24","type":"journal-article","created":{"date-parts":[[2024,10,8]],"date-time":"2024-10-08T15:44:58Z","timestamp":1728402298000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":1,"title":["Population pharmacokinetic modeling of ceftriaxone in cerebrospinal fluid in children: should we be using once- or twice-daily dosing for meningitis?"],"prefix":"10.1128","volume":"68","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9093-3992","authenticated-orcid":false,"given":"A.","family":"Boast","sequence":"first","affiliation":[{"name":"Department of General Medicine and Laboratory Services, The Royal Children\u2019s Hospital Melbourne, Parkville, Australia"},{"name":"Antimicrobials and Infectious Diseases Group, Murdoch Children\u2019s Research Institute, Melbourne, Australia"},{"name":"Department of Paediatrics, The University of Melbourne, Melbourne, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"W.","family":"Zhang","sequence":"additional","affiliation":[{"name":"Infection, Immunity and Inflammation, Great Ormond Street Institute of Child Health, University College London, London, United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"H.","family":"Soeorg","sequence":"additional","affiliation":[{"name":"Infection, Immunity and Inflammation, Great Ormond Street Institute of Child Health, University College London, London, United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"G.","family":"Gonis","sequence":"additional","affiliation":[{"name":"Department of General Medicine and Laboratory Services, The Royal Children\u2019s Hospital Melbourne, Parkville, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A.","family":"Di Carlo","sequence":"additional","affiliation":[{"name":"Department of General Medicine and Laboratory Services, The Royal Children\u2019s Hospital Melbourne, Parkville, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A.","family":"Daley","sequence":"additional","affiliation":[{"name":"Department of General Medicine and Laboratory Services, The Royal Children\u2019s Hospital Melbourne, Parkville, Australia"},{"name":"Department of Paediatrics, The University of Melbourne, Melbourne, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"N.","family":"Curtis","sequence":"additional","affiliation":[{"name":"Department of General Medicine and Laboratory Services, The Royal Children\u2019s Hospital Melbourne, Parkville, Australia"},{"name":"Antimicrobials and Infectious Diseases Group, Murdoch Children\u2019s Research Institute, Melbourne, Australia"},{"name":"Department of Paediatrics, The University of Melbourne, Melbourne, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"B.","family":"McWhinney","sequence":"additional","affiliation":[{"name":"Department of Chemical Pathology, Pathology Queensland, Brisbane, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J. P. J.","family":"Ungerer","sequence":"additional","affiliation":[{"name":"Department of Chemical Pathology, Pathology Queensland, Brisbane, Australia"},{"name":"Faculty of Health and Behavioural Sciences, University of Queensland, Brisbane, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A.","family":"Lei","sequence":"additional","affiliation":[{"name":"Antimicrobials and Infectious Diseases Group, Murdoch Children\u2019s Research Institute, Melbourne, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J. F.","family":"Standing","sequence":"additional","affiliation":[{"name":"Infection, Immunity and Inflammation, Great Ormond Street Institute of Child Health, University College London, London, United Kingdom"},{"name":"Department of Pharmacy, Great Ormond Street Hospital for Children NHS Foundation Trust, London, United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4016-8986","authenticated-orcid":false,"given":"A.","family":"Gwee","sequence":"additional","affiliation":[{"name":"Department of General Medicine and Laboratory Services, The Royal Children\u2019s Hospital Melbourne, Parkville, Australia"},{"name":"Antimicrobials and Infectious Diseases Group, Murdoch Children\u2019s Research Institute, Melbourne, Australia"},{"name":"Department of Paediatrics, The University of Melbourne, Melbourne, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"235","reference":[{"key":"e_1_3_5_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(03)13693-8"},{"key":"e_1_3_5_3_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2022.20521"},{"key":"e_1_3_5_4_2","doi-asserted-by":"publisher","DOI":"10.1086\/425368"},{"key":"e_1_3_5_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(12)61186-6"},{"key":"e_1_3_5_6_2","unstructured":"Royal children\u2019s hospital melbourne clinical practice guideline: meningitis and encephalitis [Internet]. 2022. Available from: https:\/\/www.rch.org.au\/clinicalguide\/guideline_index\/Meningitis_encephalitis\/. Retrieved 9 Apr 2024."},{"key":"e_1_3_5_7_2","volume-title":"Meningitis (bacterial) and meningococcal septicaemia in under 16s: recognition, diagnosis and management","author":"National Institute for Health and Care Excellence Clinical Guidelines, No. 102","year":"2015","unstructured":"National Institute for Health and Care Excellence Clinical Guidelines, No. 102. 2015. Meningitis (bacterial) and meningococcal septicaemia in under 16s: recognition, diagnosis and management. National Institute for Health and Care Excellence (NICE), London."},{"key":"e_1_3_5_8_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.25.4.438"},{"key":"e_1_3_5_9_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/47.4.421"},{"key":"e_1_3_5_10_2","doi-asserted-by":"publisher","DOI":"10.1128\/CMR.00007-10"},{"key":"e_1_3_5_11_2","unstructured":"\"The European Committee on Antimicrobial Susceptibility Testing. Breakpoint tables for interpretation of MICs and zone diameters. Version 14.0. 2024. Available from: https:\/\/www.eucast.org\/fileadmin\/src\/media\/PDFs\/EUCAST_files\/Breakpoint_tables\/v_14.0_Breakpoint_Tables.pdf"},{"key":"e_1_3_5_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.diagmicrobio.2020.115292"},{"key":"e_1_3_5_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijantimicag.2020.106113"},{"key":"e_1_3_5_14_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.45.1.13-22.2001"},{"key":"e_1_3_5_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijantimicag.2007.12.009"},{"key":"e_1_3_5_16_2","doi-asserted-by":"publisher","DOI":"10.1093\/clinids\/11.4.526"},{"key":"e_1_3_5_17_2","first-page":"813","article-title":"Study on the penetration of ceftriaxone into cerebrospinal fluid","volume":"49","author":"Hattori T","year":"1996","unstructured":"Hattori T, Kobayashi H, Uno T. 1996. Study on the penetration of ceftriaxone into cerebrospinal fluid. 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J Coll Physicians Surg Pak 15:165\u2013167.","journal-title":"J Coll Physicians Surg Pak"},{"key":"e_1_3_5_25_2","doi-asserted-by":"publisher","DOI":"10.1007\/s11064-021-03472-1"},{"key":"e_1_3_5_26_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00467-008-0997-5"},{"key":"e_1_3_5_27_2","doi-asserted-by":"publisher","DOI":"10.1186\/1743-8454-5-10"},{"key":"e_1_3_5_28_2","unstructured":"Joint Formulary Committee. 2024. British National Formulary [Internet]. BMJ Group and Pharmaceutical Press London. Available from: https:\/\/bnf.nice.org.uk. Retrieved 1 May 2024."},{"key":"e_1_3_5_29_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkaa363"},{"key":"e_1_3_5_30_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dky128"}],"container-title":["Antimicrobial Agents and Chemotherapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/aac.00747-24","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/aac.00747-24","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,11,6]],"date-time":"2024-11-06T13:03:01Z","timestamp":1730898181000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/aac.00747-24"}},"subtitle":[],"editor":[{"given":"Andreas H.","family":"Groll","sequence":"additional","affiliation":[],"role":[{"role":"editor","vocabulary":"crossref"}]}],"short-title":[],"issued":{"date-parts":[[2024,11,6]]},"references-count":29,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2024,11,6]]}},"alternative-id":["10.1128\/aac.00747-24"],"URL":"https:\/\/doi.org\/10.1128\/aac.00747-24","relation":{},"ISSN":["0066-4804","1098-6596"],"issn-type":[{"type":"print","value":"0066-4804"},{"type":"electronic","value":"1098-6596"}],"subject":[],"published":{"date-parts":[[2024,11,6]]},"assertion":[{"value":"2024-05-25","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-08-02","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-10-08","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e00747-24"}}