{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T13:52:31Z","timestamp":1791985951109,"version":"4.4.0"},"reference-count":27,"publisher":"American Society for Microbiology","license":[{"start":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T00:00:00Z","timestamp":1791936000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T00:00:00Z","timestamp":1791936000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"name":"German Research Council","award":["504995322"],"award-info":[{"award-number":["504995322"]}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Antimicrob Agents Chemother"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title\/>\n                    <jats:p>\n                      Sex-specific differences in pharmacokinetics are increasingly recognized as clinically relevant, yet most population pharmacokinetic models for antibiotics have been developed in predominantly male populations with limited transferability to female patients. This study aimed to develop and externally evaluate a population pharmacokinetic model of piperacillin specifically for critically ill women to support model-informed precision dosing (MIPD). A total of 923 samples from 165 critically ill women (from four previously published studies) receiving piperacillin\/tazobactam were analyzed. The data set was randomly split into a training set (80%) and an independent external evaluation set (20%). Non-linear mixed-effects modeling was employed based on the training data using NONMEM, and covariates were identified using stepwise covariate modeling with cross-validation. Prediction accuracy and bias were quantified using the median prediction error (MDPE) and the median absolute prediction error (MDAPE) in an MIPD scenario. Model predictions for future concentrations were generated both\n                      <jats:italic toggle=\"yes\">a priori<\/jats:italic>\n                      and through Bayesian forecasting based on one prior sample. A two-compartment model provided the best fit for the data. Clearance was significantly affected by renal function estimated by the Cockcroft\u2013Gault equation, along with procalcitonin and serum albumin. The external evaluation demonstrated strong predictive performance with very low systematic bias. In the MIPD scenario,\n                      <jats:italic toggle=\"yes\">a priori<\/jats:italic>\n                      predictions exhibited good predictive performance (MDPE &lt; |5.2|%, MDAPE &lt; 33.4%), which substantially improved with Bayesian forecasting (MDPE &lt; |3.2|%, MDAPE &lt; 19.1%). A female-specific population pharmacokinetic model of piperacillin was developed and externally validated, demonstrating robust predictive performance and clear benefits for Bayesian forecasting.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1128\/aac.00986-26","type":"journal-article","created":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T13:29:31Z","timestamp":1791984571000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":0,"title":["Population pharmacokinetics of piperacillin based on multicenter data to support model-informed precision dosing in critically ill women"],"prefix":"10.1128","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-6492-0486","authenticated-orcid":false,"given":"Sebastian","family":"Greppmair","sequence":"first","affiliation":[{"name":"Department of Anaesthesiology, LMU University Hospital, LMU Munich","place":["Munich, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6397-7068","authenticated-orcid":false,"given":"Sina","family":"Pesthy","sequence":"additional","affiliation":[{"name":"Department of Anaesthesiology, LMU University Hospital, LMU Munich","place":["Munich, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5337-6509","authenticated-orcid":false,"given":"Michael","family":"Zoller","sequence":"additional","affiliation":[{"name":"Department of Anaesthesiology, LMU University Hospital, LMU Munich","place":["Munich, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5310-4116","authenticated-orcid":false,"given":"Christina","family":"Scharf","sequence":"additional","affiliation":[{"name":"Department of Anaesthesiology, LMU University Hospital, LMU Munich","place":["Munich, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander","family":"Brinkmann","sequence":"additional","affiliation":[{"name":"Department of Anaesthesiology and Intensive Care Medicine, General Hospital of Heidenheim","place":["Heidenheim, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Otto","family":"Frey","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, General Hospital of Heidenheim","place":["Heidenheim, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4539-0703","authenticated-orcid":true,"given":"Johannes","family":"Zander","sequence":"additional","affiliation":[{"name":"Laboratory Dr. Brunner, Laboratory Medical Care Center Konstanz GmbH","place":["Constance, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nadine","family":"Liebchen","sequence":"additional","affiliation":[{"name":"Department of Anaesthesiology, LMU University Hospital, LMU Munich","place":["Munich, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2999-6131","authenticated-orcid":false,"given":"Stefan","family":"Hagel","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/05qpz1x62","id-type":"ROR","asserted-by":"publisher"}],"name":"Institute for Infectious Diseases and Infection Control, Jena University Hospital, Friedrich\u2010Schiller\u2010University Jena","place":["Jena, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8773-4845","authenticated-orcid":true,"given":"Sebastian G.","family":"Wicha","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/00g30e956","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Clinical Pharmacy, Institute of Pharmacy, University of Hamburg","place":["Hamburg, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2560-9598","authenticated-orcid":false,"given":"Christoph","family":"Dorn","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/01eezs655","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Pharmaceutical and Medicinal Chemistry I, University of Regensburg","place":["Regensburg, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sabrina","family":"B\u00f6ing","sequence":"additional","affiliation":[{"name":"Department of Anaesthesiology, LMU University Hospital, LMU Munich","place":["Munich, Germany"]},{"name":"Doctoral Program Clinical Pharmacy, LMU University Hospital, LMU Munich","place":["Munich, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4375-0923","authenticated-orcid":true,"given":"Uwe","family":"Liebchen","sequence":"additional","affiliation":[{"name":"Department of Anaesthesiology, LMU University Hospital, LMU Munich","place":["Munich, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","published-online":{"date-parts":[[2026,10,14]]},"reference":[{"key":"e_1_3_6_2_2","doi-asserted-by":"publisher","DOI":"10.1080\/17425255.2025.2481891"},{"key":"e_1_3_6_3_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00210-025-04721-8"},{"key":"e_1_3_6_4_2","doi-asserted-by":"publisher","DOI":"10.18549\/PharmPract.2016.01.708"},{"key":"e_1_3_6_5_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13293-020-00308-5"},{"key":"e_1_3_6_6_2","doi-asserted-by":"publisher","DOI":"10.1007\/164_2023_669"},{"key":"e_1_3_6_7_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00134-023-07154-0"},{"key":"e_1_3_6_8_2","doi-asserted-by":"publisher","DOI":"10.1002\/cpt.2202"},{"key":"e_1_3_6_9_2","doi-asserted-by":"publisher","DOI":"10.1080\/17512433.2026.2620530"},{"key":"e_1_3_6_10_2","doi-asserted-by":"publisher","DOI":"10.1007\/s40262-015-0236-8"},{"key":"e_1_3_6_11_2","doi-asserted-by":"publisher","DOI":"10.1007\/s15010-019-01352-z"},{"key":"e_1_3_6_12_2","doi-asserted-by":"publisher","DOI":"10.1097\/FTD.0000000000000827"},{"key":"e_1_3_6_13_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13054-016-1255-z"},{"key":"e_1_3_6_14_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00134-021-06609-6"},{"key":"e_1_3_6_15_2","doi-asserted-by":"publisher","DOI":"10.1159\/000180580"},{"key":"e_1_3_6_16_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2885.2012.01404.x"},{"key":"e_1_3_6_17_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.14.6.829"},{"key":"e_1_3_6_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejps.2023.106395"},{"key":"e_1_3_6_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(23)00432-2"},{"key":"e_1_3_6_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejps.2021.105814"},{"key":"e_1_3_6_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/s0009-2797(02)00006-6"},{"key":"e_1_3_6_22_2","doi-asserted-by":"publisher","DOI":"10.3390\/pharmaceutics15102427"},{"key":"e_1_3_6_23_2","doi-asserted-by":"publisher","DOI":"10.1007\/s40262-021-01013-1"},{"key":"e_1_3_6_24_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmi.2023.03.018"},{"key":"e_1_3_6_25_2","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/ciac506"},{"key":"e_1_3_6_26_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00134-020-05961-3"},{"key":"e_1_3_6_27_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00134-019-05910-9"},{"key":"e_1_3_6_28_2","unstructured":"Fachinformation: piperacillin-tazobactam-teva 4 g\/ 0 5 g. Pulver zur Herstellung einer Infusionsl\u00f6sung. Available from: https:\/\/www.fachinfo.de\/fi\/pdf\/013311. Retrieved 2121 JanJanuary 2026. Accessed 2121 JanJanuary 2026"}],"container-title":["Antimicrobial Agents and Chemotherapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/aac.00986-26","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/aac.00986-26","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T13:29:34Z","timestamp":1791984574000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/aac.00986-26"}},"subtitle":[],"editor":[{"given":"James E.","family":"Leggett","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2026,10,14]]},"references-count":27,"alternative-id":["10.1128\/aac.00986-26"],"URL":"https:\/\/doi.org\/10.1128\/aac.00986-26","relation":{},"ISSN":["0066-4804","1098-6596"],"issn-type":[{"value":"0066-4804","type":"print"},{"value":"1098-6596","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,10,14]]},"assertion":[{"value":"2026-07-26","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-09-13","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-10-14","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e00986-26"}}