{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,7]],"date-time":"2026-05-07T05:14:09Z","timestamp":1778130849516,"version":"3.51.4"},"reference-count":39,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,5,7]],"date-time":"2026-05-07T00:00:00Z","timestamp":1778112000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Although organ replacement therapy serves as a bridge to the recovery of vital organ function, it may lead to significant physiological and pharmacokinetic changes. To identify factors that may affect patient outcomes due to inadequate antimicrobial therapy, we aimed to evaluate the effectiveness of primary dosage determination of piperacillin (PIP) in the intensive care unit (ICU) setting, particularly in patients undergoing renal or lung replacement therapy.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Between January 2020 and December 2021, we retrospectively analyzed all ICU patients with a confirmed SARS-CoV-2 infection who received piperacillin\/tazobactam (PIP\/TAZ) continuous infusion due to suspected secondary infection. The analysis included a comparison of serum PIP levels, demographic data, and laboratory findings among different patient groups.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>From 108 included patients, therapeutic drug monitoring (TDM) was performed at the initiation of antibiotic treatment in 91 (84.3%) cases. Of these patients, 15 received extracorporeal membrane oxygenation (ECMO), 12 underwent continuous renal replacement therapy (CRRT), and 43 received both procedures during their ICU stay. The median age was 58 years. The in-hospital mortality rate was significantly higher in patients receiving ECMO therapy (73.3% vs. 23.8%) and in those receiving both ECMO and CRRT (72.1% vs. 23.8%) compared to patients without organ replacement procedures. Dosing calculation adjusted to renal function was correctly performed according to the established standard operating procedure in 96.7% of cases. The PIP level after primary dosage, prior to further adjustments, was within the standard operating procedure-defined concentration range of 32\u201396\u00a0mg\/L, encompassing the empirical target range and the higher exposure range relevant in specific clinical scenarios, in 59.0% [median target concentration: 44.0\u00a0mg\/L] of patients without organ support, 58.3% of those on ECMO [median target concentration: 66.8\u00a0mg\/L], 80.0% of those undergoing CRRT [median target concentration: 56.0\u00a0mg\/L], and in 27.8% of the patients receiving both ECMO and CRRT [median target concentration: 116.0\u00a0mg\/L]. In total, 17.6% of all patients did not reach the minimum PIP target level of 32\u00a0mg\/L and 27.5% were above the maximum PIP target level of 96\u00a0mg\/L. Binary regression analysis did not identify significant correlation between plasma bilirubin, plasma albumin, the capillary leak index (CLI) or anthropometric variables and achieving the target plasma concentration of PIP.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>In total, 45% of first-dose PIP concentrations in the analyzed critically ill patients were outside the recommended concentration corridor. While lowest concentrations of PIP levels were detected in critically ill patients without organ support therapy, levels above the therapeutic range were detected in patients treated with ECMO support. However, based on the data of this study, a predictor to prevent primary drug levels outside the therapeutic range was not identified. These findings underscore the critical role of TDM in daily clinical routine.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fphar.2026.1725502","type":"journal-article","created":{"date-parts":[[2026,5,7]],"date-time":"2026-05-07T04:54:43Z","timestamp":1778129683000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Effects of extracorporeal membrane oxygenation and\/or renal replacement therapy on piperacillin\/tazobactam levels in critically ill patients"],"prefix":"10.3389","volume":"17","author":[{"given":"T.","family":"Riese","sequence":"first","affiliation":[{"name":"Department of Anaesthesiology, Intensive Care, Emergency and Pain Medicine, University Hospital W\u00fcrzburg","place":["W\u00fcrzburg, Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"S.","family":"Lauter","sequence":"additional","affiliation":[{"name":"Department of Anaesthesiology, Intensive Care, Emergency and Pain Medicine, University Hospital W\u00fcrzburg","place":["W\u00fcrzburg, Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"G.","family":"Surat","sequence":"additional","affiliation":[{"name":"Unit of Infection Control and Antimicrobial Stewardship, University Hospital W\u00fcrzburg","place":["W\u00fcrzburg, Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M.","family":"Kurlbaum","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine I, Division of Endocrinology\/Diabetology, University Hospital W\u00fcrzburg","place":["W\u00fcrzburg, Germany"]},{"name":"Central Laboratory, Core Unit Clinical Mass Spectrometry, University Hospital W\u00fcrzburg","place":["W\u00fcrzburg, Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"D.","family":"Roeder","sequence":"additional","affiliation":[{"name":"Department of Anaesthesiology, Intensive Care, Emergency and Pain Medicine, University Hospital W\u00fcrzburg","place":["W\u00fcrzburg, Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"P.","family":"Meybohm","sequence":"additional","affiliation":[{"name":"Department of Anaesthesiology, Intensive Care, Emergency and Pain Medicine, University Hospital W\u00fcrzburg","place":["W\u00fcrzburg, Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"K.","family":"Hoppe","sequence":"additional","affiliation":[{"name":"Department of Anaesthesiology, Intensive Care, Emergency and Pain Medicine, University Hospital W\u00fcrzburg","place":["W\u00fcrzburg, Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2026,5,7]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1127","DOI":"10.1007\/s00134-020-06050-1","article-title":"Antimicrobial therapeutic drug monitoring in critically ill adult patients: a position paper","volume":"46","author":"Abdul-Aziz","year":"2020","journal-title":"Intensive Care Med."},{"key":"B2","doi-asserted-by":"publisher","first-page":"414","DOI":"10.1001\/jamainternmed.2023.8225","article-title":"COVID-19\u2212Associated acute kidney injury and longitudinal kidney outcomes","volume":"184","author":"Aklilu","year":"2024","journal-title":"JAMA Intern Med."},{"key":"B3","doi-asserted-by":"publisher","first-page":"31","DOI":"10.1186\/s13000-021-01092-5","article-title":"Hypoproteinemia predicts disease severity and mortality in COVID-19: a call for action","volume":"16","author":"Ali","year":"2021","journal-title":"Diagn Pathol."},{"key":"B4","doi-asserted-by":"publisher","first-page":"2090792","DOI":"10.1080\/21688370.2022.2090792","article-title":"Roles of the ACE\/ang II\/AT1R pathway, cytokine release, and alteration of tight junctions in COVID-19 pathogenesis","volume":"11","author":"Ashour","year":"2023","journal-title":"Tissue Barriers"},{"key":"B5","doi-asserted-by":"publisher","first-page":"788","DOI":"10.1001\/jama.2016.0291","article-title":"Epidemiology, patterns of care, and mortality for patients with acute respiratory distress syndrome in intensive care units in 50 countries","volume":"315","author":"Bellani","year":"2016","journal-title":"JAMA"},{"key":"B6","doi-asserted-by":"publisher","first-page":"115","DOI":"10.1067\/mcp.2002.121829","article-title":"Changes in plasma protein binding have little clinical relevance","volume":"71","author":"Benet","year":"2002","journal-title":"Clin. Pharmacol. Ther."},{"key":"B7","doi-asserted-by":"publisher","first-page":"75","DOI":"10.1016\/S0140-6736(18)30696-2","article-title":"Sepsis and septic shock","volume":"392","author":"Cecconi","year":"2018","journal-title":"Lancet"},{"key":"B8","doi-asserted-by":"publisher","first-page":"667","DOI":"10.3390\/antibiotics10060667","article-title":"Personalized piperacillin dosing for the critically ill: a retrospective analysis of clinical experience with dosing software and therapeutic drug monitoring to optimize antimicrobial dosing","volume":"10","author":"Chiriac","year":"2021","journal-title":"Antibiotics"},{"key":"B9","doi-asserted-by":"publisher","first-page":"S1","DOI":"10.1186\/2110-5820-2-S1-S1","article-title":"Fluid management in critically ill patients: the role of extravascular lung water, abdominal hypertension, capillary leak, and fluid balance","volume":"2","author":"Cordemans","year":"2012","journal-title":"Ann Intensive Care"},{"key":"B10","doi-asserted-by":"publisher","first-page":"380","DOI":"10.1007\/s00134-013-3187-2","article-title":"Therapeutic drug monitoring-based dose optimisation of piperacillin and meropenem: a randomised controlled trial","volume":"40","author":"De Waele","year":"2014","journal-title":"Inensive Care Med."},{"key":"B11","doi-asserted-by":"publisher","first-page":"1171","DOI":"10.1007\/s40264-017-0578-2","article-title":"Neurological adverse effects attributable to \u03b2-Lactam antibiotics: a literature review","volume":"40","author":"Deshayes","year":"2017","journal-title":"Drug Saf."},{"key":"B12","doi-asserted-by":"publisher","first-page":"37","DOI":"10.1007\/s00063-020-00685-0","article-title":"S3-Leitlinie Sepsis \u2013 pr\u00e4vention, Diagnose, Therapie und Nachsorge: langfassung","volume":"115","author":"Deutsche Sepsis Gesellschaft","year":"2020","journal-title":"Med. Klin. - Intensivmed. Notfallmedizin"},{"key":"B13","doi-asserted-by":"publisher","first-page":"75","DOI":"10.1016\/j.jcrc.2019.04.013","article-title":"Early target attainment of continous infusion piperacillin\/tazobactam and meropenem in critially ill patients: a prospective observational study","volume":"52","author":"Dhaese","year":"2019","journal-title":"J. Crit Care"},{"key":"B14","doi-asserted-by":"publisher","first-page":"278","DOI":"10.1016\/j.ijantimicag.2014.11.005","article-title":"\u03b2-Lactam pharmacokinetics during extracorporeal membrane oxygenation therapy: a case\u2013control study","volume":"45","author":"Donadello","year":"2015","journal-title":"Int. J. Antimicrob. Agents"},{"key":"B15","doi-asserted-by":"publisher","first-page":"926","DOI":"10.1164\/rccm.202207-1258ED","article-title":"Insights into endotheliopathy in COVID-19","volume":"206","author":"Filbin","year":"2022","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"B16","doi-asserted-by":"publisher","first-page":"338","DOI":"10.3390\/antibiotics11030338","article-title":"Antibiotics and ECMO in the adult population\u2014persistent challenges and practical guides","volume":"11","author":"Gomez","year":"2022","journal-title":"Antibiotics"},{"key":"B17","doi-asserted-by":"publisher","first-page":"R206","DOI":"10.1186\/cc10441","article-title":"Antibiotics in critically ill patients: a systematic review of the pharmacokinetics of \u03b2-lactams","volume":"15","author":"Gon\u00e7alves-Pereira","year":"2011","journal-title":"Crit. Care"},{"key":"B18","doi-asserted-by":"publisher","first-page":"104","DOI":"10.1186\/s13054-019-2378-9","article-title":"Optimization of the treatment with beta-lactam antibiotics in critically ill patients\u2014guidelines from the French Society of Pharmacology and Therapeutics (Soci\u00e9t\u00e9 Fran\u00e7aise de Pharmacologie et Th\u00e9rapeutique\u2014SFPT) and the French Society of Anaesthesia and Intensive Care Medicine (Soci\u00e9t\u00e9 Fran\u00e7aise d\u2019Anesth\u00e9sie et R\u00e9animation\u2014SFAR)","volume":"23","author":"Guilhaumou","year":"2019","journal-title":"Crit. Care"},{"key":"B19","doi-asserted-by":"publisher","first-page":"311","DOI":"10.1007\/s00134-021-06609-6","article-title":"Effect of therapeutic drug monitoring-based dose optimization of piperacillin\/tazobactam on sepsis-related organ dysfunction in patients with sepsis: a randomized controlled trial","volume":"48","author":"Hagel","year":"2022","journal-title":"Intensive Care Med."},{"key":"B20","doi-asserted-by":"publisher","first-page":"1411","DOI":"10.1007\/s00134-015-3934-7","article-title":"Epidemiology of acute kidney injury in critically ill patients: the multinational AKI-EPI study","volume":"41","author":"Hoste","year":"2015","journal-title":"Intensive Care Med."},{"key":"B21","doi-asserted-by":"publisher","first-page":"24379","DOI":"10.1038\/s41598-021-03865-w","article-title":"Effect of hypoproteinemia on the mortality of sepsis patients in the ICU: a retrospective cohort study","volume":"11","author":"Hu","year":"2021","journal-title":"Sci. Rep."},{"key":"B22","doi-asserted-by":"publisher","first-page":"1678","DOI":"10.1007\/s11427-020-1733-4","article-title":"Decreased serum albumin level indicates poor prognosis of COVID-19 patients: hepatic injury analysis from 2,623 hospitalized cases","volume":"63","author":"Huang","year":"2020","journal-title":"Sci. China Life Sci."},{"key":"B23","doi-asserted-by":"publisher","first-page":"1640","DOI":"10.1097\/CCM.0000000000000317","article-title":"The impact of variation in renal replacement therapy settings on piperacillin, meropenem, and vancomycin drug clearance in the critically ill: an analysis of published literature and dosing regimens","volume":"42","author":"Jamal","year":"2014","journal-title":"Crit. Care Med."},{"key":"B24","doi-asserted-by":"publisher","first-page":"664","DOI":"10.1186\/s13054-020-03397-1","article-title":"Antibiotic therapeutic drug monitoring in intensive care patients treated with different modalities of extracorporeal membrane oxygenation (ECMO) and renal replacement therapy: a prospective, observational single-center study","volume":"24","author":"K\u00fchn","year":"2020","journal-title":"Crit. Care"},{"key":"B25","doi-asserted-by":"publisher","first-page":"1589","DOI":"10.1097\/01.CCM.0000217961.75225.E9","article-title":"Duration of hypotension before initiation of effective antimicrobial therapy is the critical determinant of survival in human septic shock","volume":"34","author":"Kumar","year":"2006","journal-title":"Crit. Care Med."},{"key":"B26","doi-asserted-by":"publisher","first-page":"622","DOI":"10.1016\/S0140-6736(21)00439-6","article-title":"Acute respiratory distress syndrome","volume":"398","author":"Meyer","year":"2021","journal-title":"Lancet"},{"key":"B27","doi-asserted-by":"publisher","first-page":"1452","DOI":"10.3390\/antibiotics10121452","article-title":"Personalized antibiotic therapy for the critically ill: implementation strategies and effects on clinical outcome of piperacillin therapeutic drug monitoring\u2014A descriptive retrospective analysis","volume":"10","author":"Nikolas","year":"2021","journal-title":"Antibiotics"},{"key":"B28","doi-asserted-by":"publisher","first-page":"1001","DOI":"10.1007\/s15010-019-01352-z","article-title":"Therapeutic drug monitoring-guided continuous infusion of piperacillin\/tazobactam significantly improves pharmacokinetic target attainment in critically ill patients: a retrospective analysis of four years of clinical experience","volume":"47","author":"Richter","year":"2019","journal-title":"Infection"},{"key":"B29","doi-asserted-by":"publisher","first-page":"1523","DOI":"10.1097\/CCM.0b013e318241e553","article-title":"Variability of antibiotic concentrations in critically ill patients receiving continuous renal replacement therapy: a multicentre pharmacokinetic study","volume":"40","author":"Roberts","year":"2012","journal-title":"Crit. Care Med."},{"key":"B30","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1007\/s40262-012-0018-5","article-title":"The clinical relevance of plasma protein binding changes","volume":"52","author":"Roberts","year":"2013","journal-title":"Clin. Pharmacokinet."},{"key":"B31","doi-asserted-by":"publisher","first-page":"1369","DOI":"10.1093\/cid\/ciaa224","article-title":"The effect of renal replacement therapy and antibiotic dose on antibiotic concentrations in critically ill patients: data from the multinational sampling antibiotics in renal replacement therapy study","volume":"72","author":"Roberts","year":"2021","journal-title":"Clin. Infect. Dis."},{"key":"B32","doi-asserted-by":"publisher","first-page":"86","DOI":"10.1186\/s40560-020-00504-w","article-title":"The higher the better ? Defining the optimal beta-lactam target for critically ill patients to reach infection resolution and improve outcome","volume":"8","author":"Scharf","year":"2020","journal-title":"J. Intensive Care"},{"key":"B33","doi-asserted-by":"publisher","first-page":"e9","DOI":"10.1016\/j.jcrc.2012.02.013","article-title":"Pharmacokinetic changes in patients receiving extracorporeal membrane oxygenation","volume":"27","author":"Shekar","year":"2012","journal-title":"J. Crit. Care"},{"key":"B34","doi-asserted-by":"publisher","first-page":"83","DOI":"10.1016\/j.xkme.2020.11.008","article-title":"The prevalence of acute kidney injury in patients hospitalized with COVID-19 infection: a systematic review and meta-analysis","volume":"3","author":"Silver","year":"2021","journal-title":"Kidney Med."},{"key":"B35","doi-asserted-by":"publisher","first-page":"801","DOI":"10.1001\/jama.2016.0287","article-title":"The third international consensus definitions for sepsis and septic shock (Sepsis-3)","volume":"315","author":"Singer","year":"2016","journal-title":"JAMA"},{"key":"B36","doi-asserted-by":"publisher","first-page":"1647","DOI":"10.1093\/jac\/dky057","article-title":"Pharmacokinetics of piperacillin in critically ill patients with acute kidney injury receiving sustained low-efficiency diafiltration","volume":"73","author":"Sinnollareddy","year":"2018","journal-title":"J. Antimicrob. Chemother."},{"key":"B37","doi-asserted-by":"publisher","first-page":"S14","DOI":"10.1007\/BF01745246","article-title":"Pharmacokinetic characteristics of piperacillin\/tazobactam","volume":"20","author":"S\u00f6rgel","year":"1994","journal-title":"Intensive Care Med."},{"key":"B38","doi-asserted-by":"publisher","first-page":"175","DOI":"10.1186\/s13613-021-00965-8","article-title":"Diagnosing capillary leak in critically ill patients: development of an innovative scoring instrument for non-invasive detection","volume":"11","author":"Wollborn","year":"2021","journal-title":"Ann. Intensive Care"},{"key":"B39","doi-asserted-by":"publisher","first-page":"695","DOI":"10.1038\/s41401-022-00998-0","article-title":"Endothelial dysfunction in COVID-19: an overview of evidence, biomarkers, mechanisms and potential therapies","volume":"44","author":"Xu","year":"2023","journal-title":"Acta Pharmacol. Sin."}],"container-title":["Frontiers in Pharmacology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2026.1725502\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,7]],"date-time":"2026-05-07T04:54:48Z","timestamp":1778129688000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2026.1725502\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,7]]},"references-count":39,"alternative-id":["10.3389\/fphar.2026.1725502"],"URL":"https:\/\/doi.org\/10.3389\/fphar.2026.1725502","relation":{},"ISSN":["1663-9812"],"issn-type":[{"value":"1663-9812","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,7]]},"article-number":"1725502"}}