{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T15:39:26Z","timestamp":1792510766577,"version":"4.5.0"},"reference-count":35,"publisher":"American Society for Microbiology","issue":"10","license":[{"start":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T00:00:00Z","timestamp":1791331200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T00:00:00Z","timestamp":1791331200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"name":"Children's Health Queensland","award":["50225"],"award-info":[{"award-number":["50225"]}],"id":[{"id":"https:\/\/ror.org\/02t3p7e85","id-type":"ROR","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","award":["APP1142757"],"award-info":[{"award-number":["APP1142757"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","award":["APP2007007"],"award-info":[{"award-number":["APP2007007"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","award":["APP2009736"],"award-info":[{"award-number":["APP2009736"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[2026,10,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title\/>\n                    <jats:p>Piperacillin-tazobactam is commonly used in critically ill pediatric patients; however, standard dosing regimens may not reliably achieve maximally effective exposures in this population. To characterize the population pharmacokinetics of piperacillin-tazobactam in critically ill pediatric patients and evaluate the adequacy of commonly used dosing regimens, plasma concentrations were obtained around a single dose of piperacillin-tazobactam in critically ill pediatric patients aged 1 month to 12 years. A simultaneous population pharmacokinetic model for piperacillin and tazobactam was developed using nonlinear mixed-effects modeling. Monte Carlo simulations were performed to assess the probability of target attainment (PTA) for short, extended, and continuous infusion regimens across a range of ages and renal function states. Dosing adequacy was defined by simultaneous attainment of target drug exposures for piperacillin (100%fT &gt; MIC) and tazobactam (85%fT &gt; 2 mg\/L). Thirty-one patients contributed 102 plasma samples, of which only 22.6% of patients achieved simultaneous piperacillin-tazobactam target exposures, considering a piperacillin MIC of 16 mg\/L. Renal function and infusion duration were the primary determinants of attainment of target attainment. Standard short infusions frequently failed to achieve combined target exposures, particularly in patients with preserved renal function or augmented renal clearance (ARC). Extended infusions improved PTA, but remained suboptimal at higher MICs. Continuous infusion consistently achieved the highest target drug exposures across all simulated scenarios. Short intermittent piperacillin-tazobactam infusions and even extended infusions often result in suboptimal exposure in critically ill pediatric patients. Continuous infusion represents a rational dosing strategy to improve combined target attainment, particularly in children with preserved or ARC.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1128\/aac.00272-26","type":"journal-article","created":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T14:04:20Z","timestamp":1788444260000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":0,"title":["Population pharmacokinetics of piperacillin\/tazobactam in critically ill pediatric patients"],"prefix":"10.1128","volume":"70","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5030-7535","authenticated-orcid":true,"given":"Tavey","family":"Dorofaeff","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/00rqy9422","id-type":"ROR","asserted-by":"publisher"}],"name":"Frazer Institute, The University of Queensland","place":["Brisbane, Australia"]},{"id":[{"id":"https:\/\/ror.org\/02t3p7e85","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Pediatric Intensive Care, Queensland Children's Hospital","place":["Brisbane, Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3565-0292","authenticated-orcid":true,"given":"Mar\u00eda Patricia","family":"Hern\u00e1ndez-Mitre","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/00rqy9422","id-type":"ROR","asserted-by":"publisher"}],"name":"Frazer Institute, The University of Queensland","place":["Brisbane, Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6210-8100","authenticated-orcid":true,"given":"Xin","family":"Liu","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/00rqy9422","id-type":"ROR","asserted-by":"publisher"}],"name":"Frazer Institute, The University of Queensland","place":["Brisbane, Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yarmarly C.","family":"Guerra Valero","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/00rqy9422","id-type":"ROR","asserted-by":"publisher"}],"name":"Frazer Institute, The University of Queensland","place":["Brisbane, Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7400-5582","authenticated-orcid":true,"given":"Mark G.","family":"Coulthard","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02t3p7e85","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Pediatric Intensive Care, Queensland Children's Hospital","place":["Brisbane, Australia"]},{"id":[{"id":"https:\/\/ror.org\/00rqy9422","id-type":"ROR","asserted-by":"publisher"}],"name":"Faculty of Health Medicine and Behavioural Sciences, The University of Queensland","place":["Brisbane, Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5965-9876","authenticated-orcid":true,"given":"Jeffrey","family":"Lipman","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/00rqy9422","id-type":"ROR","asserted-by":"publisher"}],"name":"Frazer Institute, The University of Queensland","place":["Brisbane, Australia"]},{"id":[{"id":"https:\/\/ror.org\/05p52kj31","id-type":"ROR","asserted-by":"publisher"}],"name":"Jamieson Trauma Institute, Royal Brisbane & Women\u2019s Hospital","place":["Brisbane, Australia"]},{"id":[{"id":"https:\/\/ror.org\/051escj72","id-type":"ROR","asserted-by":"publisher"}],"name":"Division of Anesthesia Critical Care, Pain and Emergency Medicine, UR-UM104 IMAGINE, University of Montpellier, Nimes University Hospital","place":["Montpellier, France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2392-9854","authenticated-orcid":true,"given":"Steven C.","family":"Wallis","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/00rqy9422","id-type":"ROR","asserted-by":"publisher"}],"name":"Frazer Institute, The University of Queensland","place":["Brisbane, Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7901-6790","authenticated-orcid":true,"given":"Diane L.","family":"Maresco-Pennisi","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/00rqy9422","id-type":"ROR","asserted-by":"publisher"}],"name":"Frazer Institute, The University of Queensland","place":["Brisbane, Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6124-7475","authenticated-orcid":true,"given":"Suzane L.","family":"Parker","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/00rqy9422","id-type":"ROR","asserted-by":"publisher"}],"name":"Frazer Institute, The University of Queensland","place":["Brisbane, Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jason A.","family":"Roberts","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/00rqy9422","id-type":"ROR","asserted-by":"publisher"}],"name":"Frazer Institute, The University of Queensland","place":["Brisbane, Australia"]},{"id":[{"id":"https:\/\/ror.org\/05p52kj31","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Intensive Care Medicine, Royal Brisbane & Women\u2019s Hospital","place":["Brisbane, Australia"]},{"name":"Department of Pharmacy, Royal Brisbane & Women\u2019s Hospital","place":["Brisbane, Australia"]},{"id":[{"id":"https:\/\/ror.org\/03a0hqz22","id-type":"ROR","asserted-by":"publisher"}],"name":"Herston Infectious Diseases Institute (HeIDI), Metro North Health","place":["Brisbane, Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1002\/j.1875-9114.1982.tb03202.x"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1093\/ajhp\/52.6_Suppl_2.S29"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijantimicag.2003.10.012"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1002\/phar.2210"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.1080\/14787210.2019.1647781"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.1097\/PCC.0000000000001535"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.1517\/17425250802614688"},{"key":"e_1_3_4_9_2","doi-asserted-by":"publisher","DOI":"10.1007\/s40262-018-0682-1"},{"key":"e_1_3_4_10_2","doi-asserted-by":"publisher","DOI":"10.1111\/bcp.14505"},{"key":"e_1_3_4_11_2","doi-asserted-by":"publisher","DOI":"10.3390\/antibiotics9060329"},{"key":"e_1_3_4_12_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkx093"},{"key":"e_1_3_4_13_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00431-022-04716-0"},{"key":"e_1_3_4_14_2","doi-asserted-by":"publisher","DOI":"10.1007\/s40262-019-00813-w"},{"key":"e_1_3_4_15_2","doi-asserted-by":"publisher","DOI":"10.5863\/1551-6776-22.3.212"},{"key":"e_1_3_4_16_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01260-19"},{"key":"e_1_3_4_17_2","doi-asserted-by":"publisher","DOI":"10.1097\/PCC.0000000000002951"},{"key":"e_1_3_4_18_2","doi-asserted-by":"publisher","DOI":"10.3390\/antibiotics10101182"},{"key":"e_1_3_4_19_2","doi-asserted-by":"publisher","DOI":"10.1097\/INF.0000000000004054"},{"key":"e_1_3_4_20_2","doi-asserted-by":"publisher","DOI":"10.1097\/INF.0b013e3182a743c7"},{"key":"e_1_3_4_21_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.02089-15"},{"key":"e_1_3_4_22_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkaf457"},{"key":"e_1_3_4_23_2","doi-asserted-by":"publisher","DOI":"10.1002\/pbc.22051"},{"key":"e_1_3_4_24_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2024.9779"},{"key":"e_1_3_4_25_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijantimicag.2009.10.008"},{"key":"e_1_3_4_26_2","doi-asserted-by":"publisher","DOI":"10.1097\/CCM.0b013e3181968e44"},{"key":"e_1_3_4_27_2","doi-asserted-by":"publisher","DOI":"10.24875\/RIC.19002943"},{"key":"e_1_3_4_28_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00467-023-06221-4"},{"key":"e_1_3_4_29_2","unstructured":"US Food and Drug Administration. 2018. Bioanalytical method validation: guidance for industry. U.S. Department of Health and Human Services Food and Drug Administration Center for Drug Evaluation and Research (CDER) Center for Veterinary Medicine (CVM) Silver Spring MD. https:\/\/www.fda.gov\/files\/drugs\/published\/Bioanalytical-Method-Validation-Guidance-for-Industry.pdf."},{"key":"e_1_3_4_30_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpba.2017.10.023"},{"key":"e_1_3_4_31_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00134-020-06050-1"},{"key":"e_1_3_4_32_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkx209"},{"key":"e_1_3_4_33_2","doi-asserted-by":"publisher","DOI":"10.1128\/aac.01253-25"},{"key":"e_1_3_4_34_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00654-17"},{"key":"e_1_3_4_35_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2024.21972"},{"key":"e_1_3_4_36_2","doi-asserted-by":"publisher","DOI":"10.1007\/s40262-015-0236-8"}],"container-title":["Antimicrobial Agents and Chemotherapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/aac.00272-26","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/aac.00272-26","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T14:49:39Z","timestamp":1792507779000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/aac.00272-26"}},"subtitle":[],"editor":[{"given":"Pranita D.","family":"Tamma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2026,10,7]]},"references-count":35,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2026,10,7]]}},"alternative-id":["10.1128\/aac.00272-26"],"URL":"https:\/\/doi.org\/10.1128\/aac.00272-26","relation":{},"ISSN":["0066-4804","1098-6596"],"issn-type":[{"value":"0066-4804","type":"print"},{"value":"1098-6596","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,10,7]]},"assertion":[{"value":"2026-02-18","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-07-24","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-09-03","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e00272-26"}}