{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,19]],"date-time":"2026-06-19T10:52:28Z","timestamp":1781866348333,"version":"3.54.5"},"reference-count":36,"publisher":"Oxford University Press (OUP)","issue":"7","license":[{"start":{"date-parts":[[2026,6,19]],"date-time":"2026-06-19T00:00:00Z","timestamp":1781827200000},"content-version":"vor","delay-in-days":16,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"Australian National Health and Medical Research Council","award":["APP2009736"],"award-info":[{"award-number":["APP2009736"]}]},{"name":"Advancing Queensland Clinical Fellowship"},{"name":"University Malaya Private","award":["PV023-2017"],"award-info":[{"award-number":["PV023-2017"]}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82003860"],"award-info":[{"award-number":["82003860"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100015401","name":"Key Research and Development Program of Shaanxi","doi-asserted-by":"publisher","award":["2024SF-YBXM-277"],"award-info":[{"award-number":["2024SF-YBXM-277"]}],"id":[{"id":"10.13039\/501100015401","id-type":"DOI","asserted-by":"publisher"}]},{"name":"IIT Clinical Research Fund"},{"name":"Hospital of Xi'an Jiaotong University","award":["M097"],"award-info":[{"award-number":["M097"]}]},{"DOI":"10.13039\/501100003093","name":"Ministry of Higher Education of Malaysia","doi-asserted-by":"crossref","award":["FRGS16-048-0547"],"award-info":[{"award-number":["FRGS16-048-0547"]}],"id":[{"id":"10.13039\/501100003093","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Australian National Health and Medical Research Council Centre of Research Excellence","award":["APP2007007"],"award-info":[{"award-number":["APP2007007"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,6,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>To characterize the population pharmacokinetics and pharmacokinetic\/pharmacodynamic target attainment of piperacillin and tazobactam in critically ill patients with sepsis or septic shock in Malaysian intensive care units and to use the population pharmacokinetic model to estimate individual target attainment and explore associations with clinical outcomes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Serial blood samples were collected on days 1 and 3 of therapy in this prospective multicentre study. Total plasma piperacillin and tazobactam concentrations were quantified using a validated chromatographic assay. Population pharmacokinetic analysis and Monte Carlo dosing simulations were performed using Monolix. Therapeutic exposure was defined as achieving 100% fT&amp;gt;16 mg\/L for piperacillin and 85% fT&amp;gt;2 mg\/L for tazobactam while remaining below the piperacillin toxicity threshold (&amp;lt;160\u2005mg\/L).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Forty-five critically ill adults with sepsis or septic shock were recruited (median age, 61\u2005years [range: 18\u201388]; median creatinine clearance (CLcr) 70\u2005mL\/min [range: 30\u2013161]; 20 females). A one-compartment model with first-order elimination best described the pharmacokinetics for both drugs. Estimated CLcr significantly influenced drug clearance. Pre-defined therapeutic exposures were achieved in 54% and 44% on days 1 and 3, respectively. Patients attaining exposures were older and had lower CLcr. Clinical cure and ICU survival were numerically different across exposure groups, although these exploratory comparisons were not statistically significant. Simulations indicated that a 4.5\u2005g loading dose followed by 4.5\u2005g every 6\u2005h as a continuous infusion achieved effective and safe exposures in patients with CLcr 50 to 130\u2005mL\/min.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Continuous infusion is the most reliable strategy for achieving early piperacillin\/tazobactam therapeutic exposures in patients with sepsis or septic shock.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/jac\/dkag199","type":"journal-article","created":{"date-parts":[[2026,5,28]],"date-time":"2026-05-28T11:42:31Z","timestamp":1779968551000},"source":"Crossref","is-referenced-by-count":0,"title":["A multicentre evaluation of pharmacokinetic\/pharmacodynamic target attainment of piperacillin and tazobactam and the association with clinical outcomes in critically ill patients with sepsis and septic shock"],"prefix":"10.1093","volume":"81","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7541-6615","authenticated-orcid":false,"given":"Helmi","family":"Sulaiman","sequence":"first","affiliation":[{"name":"Infectious Diseases Unit, Department of Medicine, Faculty of Medicine, Universiti Malaya , Kuala Lumpur ,","place":["Malaysia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saskia A","family":"W\u00f6lky","sequence":"additional","affiliation":[{"name":"Hospital Pharmacy, Heidelberg University Hospital , Heidelberg ,","place":["Germany"]},{"name":"Frazer Institute, Faculty of Health, Medicine, and Behavioural Sciences, The University of Queensland , Brisbane ,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muhammad Azrai","family":"Rozali","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Kulliyyah of Pharmacy, International Islamic University Malaysia (IIUM) , Kuantan ,","place":["Malaysia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Santosh K S","family":"Adiraju","sequence":"additional","affiliation":[{"name":"Frazer Institute, Faculty of Health, Medicine, and Behavioural Sciences, The University of Queensland , Brisbane ,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7493-7416","authenticated-orcid":false,"given":"M Shahnaz","family":"Hasan","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Faculty of Medicine, Universiti Malaya , Kuala Lumpur ,","place":["Malaysia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3565-0292","authenticated-orcid":false,"given":"Maria Patricia","family":"Hernandez-Mitre","sequence":"additional","affiliation":[{"name":"Frazer Institute, Faculty of Health, Medicine, and Behavioural Sciences, The University of Queensland , Brisbane ,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6210-8100","authenticated-orcid":false,"given":"Xin","family":"Liu","sequence":"additional","affiliation":[{"name":"Frazer Institute, Faculty of Health, Medicine, and Behavioural Sciences, The University of Queensland , Brisbane ,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohd-Basri","family":"Mat-Nor","sequence":"additional","affiliation":[{"name":"Department of Anaesthesiology and Intensive Care, Kulliyyah of Medicine, International Islamic University Malaysia (IIUM) , Kuantan ,","place":["Malaysia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohd Zulfakar","family":"Mazlan","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology and Intensive Care, School of Medical Sciences, Universiti Sains Malaysia , Kota Bharu ,","place":["Malaysia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zeti Norfidiyati","family":"Salmuna","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology and Parasitology, School of Medical Sciences, Universiti Sains Malaysia , Kota Bharu ,","place":["Malaysia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2392-9854","authenticated-orcid":false,"given":"Steven C","family":"Wallis","sequence":"additional","affiliation":[{"name":"Frazer Institute, Faculty of Health, Medicine, and Behavioural Sciences, The University of Queensland , Brisbane ,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7115-829X","authenticated-orcid":false,"given":"Jiao","family":"Xie","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, The Second Affiliated Hospital of Xi\u2019an Jiaotong University , Xi\u2019an 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