{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T19:09:47Z","timestamp":1792177787674,"version":"4.4.0"},"reference-count":58,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2025,4,21]],"date-time":"2025-04-21T00:00:00Z","timestamp":1745193600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Instituto de Investigaci\u00f3n Sanitaria INCLIVA"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antibiotics"],"abstract":"<jats:p>Background: Sepsis is a major global health issue and the leading cause of death in critically ill patients, with rising incidence and associated healthcare costs. Early administration of antibiotic therapy is crucial, but increasing antibiotic resistance poses a threat. Beta-lactam antibiotics, commonly used as a first-line therapy option against sepsis, often demonstrate unpredictable concentrations due to pharmacokinetic and pharmacodynamic changes in critically ill patients. Acute kidney injury (AKI) affects a significant portion of septic patients, and continuous renal replacement therapy can further complicate treatment by reducing antibiotic levels and, consequently, increasing antibiotic resistance risk. Objectives: To develop pharmacokinetic\/pharmacodynamic models for beta-lactam antibiotics in septic shock patients undergoing continuous renal replacement therapy (CRRT), with the goal of optimizing antibiotic dosing and then improving treatment outcomes. Methods: Septic shock Caucasian adult patients treated with beta-lactams and who have undergone major surgery in AKI failure that requires CRRT will be eligible with previous informed written consent. CRRT will be performed exclusively using Continuous Venovenous Hemodiafiltration (CVVHDF) modality. Antimicrobial determination analyses will be carried out with LC-MS\/MS. Further calculation of pharmacokinetic parameters and determination of PK\/PD breakpoints will be made using Monte Carlo simulation. Conclusions: The expected results from this study will lead to a better understanding of the pharmacokinetics of beta-lactam antibiotics in critically ill patients with AKI and septic shock undergoing CVVHDF, allowing for improved therapeutic strategies.<\/jats:p>","DOI":"10.3390\/antibiotics14040420","type":"journal-article","created":{"date-parts":[[2025,4,21]],"date-time":"2025-04-21T20:42:00Z","timestamp":1745268120000},"page":"420","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Antimicrobial Dosing During Continuous Venovenous Hemodiafiltration in Septic Shock Patients: A Prospective, Multicenter Study Protocol"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-4727-1498","authenticated-orcid":false,"given":"Alicia Wendy","family":"Vega Harwood","sequence":"first","affiliation":[{"name":"Critical Care Unit, Anesthesiology and Critical Care Department, Clinic University Hospital of Valladolid, 47003 Valladolid, Spain"},{"name":"BioCritic, Group for Biomedical Research in Critical Care Medicine, 47003 Valladolid, Spain"},{"name":"Personalizing Antimicrobials in Critical Care Unit (PACCU) Network, 46010 Valencia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marta Mart\u00edn","family":"Fern\u00e1ndez","sequence":"additional","affiliation":[{"name":"BioCritic, Group for Biomedical Research in Critical Care Medicine, 47003 Valladolid, Spain"},{"name":"Personalizing Antimicrobials in Critical Care Unit (PACCU) Network, 46010 Valencia, Spain"},{"name":"Pharmacology, Faculty of Medicine, University of Valladolid, 47005 Valladolid, Spain"},{"name":"Center for Biomedical Research Network on Infection Diseases (CIBERINFEC), Instituto de Salud Carlos III, 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4457-8843","authenticated-orcid":false,"given":"Carlos","family":"Ezquer Garin","sequence":"additional","affiliation":[{"name":"Personalizing Antimicrobials in Critical Care Unit (PACCU) Network, 46010 Valencia, Spain"},{"name":"Institute for Health Research (INCLIVA), Clinic University Hospital of Valencia, 46010 Valencia, Spain"},{"name":"Central Unit for Medical Research of the School of Medicine (UCIM), University of Valencia, 46010 Valencia, Spain"},{"name":"Department of Pharmacy, Clinic University Hospital of Valencia, 46010 Valencia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7566-5678","authenticated-orcid":false,"given":"Francisco Javier","family":"\u00c1lvarez","sequence":"additional","affiliation":[{"name":"BioCritic, Group for Biomedical Research in Critical Care Medicine, 47003 Valladolid, Spain"},{"name":"Personalizing Antimicrobials in Critical Care Unit (PACCU) Network, 46010 Valencia, Spain"},{"name":"Pharmacology, Faculty of Medicine, University of Valladolid, 47005 Valladolid, Spain"},{"name":"Center for Biomedical Research Network on Infection Diseases (CIBERINFEC), Instituto de Salud Carlos III, 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0295-7071","authenticated-orcid":false,"given":"Roc\u00edo","family":"L\u00f3pez Herrero","sequence":"additional","affiliation":[{"name":"Critical Care Unit, Anesthesiology and Critical Care Department, Clinic University Hospital of Valladolid, 47003 Valladolid, Spain"},{"name":"BioCritic, Group for Biomedical Research in Critical Care Medicine, 47003 Valladolid, Spain"},{"name":"Personalizing Antimicrobials in Critical Care Unit (PACCU) Network, 46010 Valencia, Spain"},{"name":"Center for Biomedical Research Network on Infection Diseases (CIBERINFEC), Instituto de Salud Carlos III, 28029 Madrid, Spain"},{"name":"Department of Surgery, University of Valladolid, 47003 Valladolid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8900-0944","authenticated-orcid":false,"given":"Eduardo","family":"Tamayo","sequence":"additional","affiliation":[{"name":"Critical Care Unit, Anesthesiology and Critical Care Department, Clinic University Hospital of Valladolid, 47003 Valladolid, Spain"},{"name":"BioCritic, Group for Biomedical Research in Critical Care Medicine, 47003 Valladolid, Spain"},{"name":"Personalizing Antimicrobials in Critical Care Unit (PACCU) Network, 46010 Valencia, Spain"},{"name":"Center for Biomedical Research Network on Infection Diseases (CIBERINFEC), Instituto de Salud Carlos III, 28029 Madrid, Spain"},{"name":"Department of Surgery, University of Valladolid, 47003 Valladolid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7997-4294","authenticated-orcid":false,"given":"Gerardo","family":"Aguilar","sequence":"additional","affiliation":[{"name":"Personalizing Antimicrobials in Critical Care Unit (PACCU) Network, 46010 Valencia, Spain"},{"name":"Institute for Health Research (INCLIVA), Clinic University Hospital of Valencia, 46010 Valencia, Spain"},{"name":"Critical Care Unit, Anesthesiology and Critical Care Department, Clinic University Hospital of Valencia, 46010 Valencia, Spain"},{"name":"Department of Surgery, School of Medicine, University of Valencia, 46010 Valencia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,4,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1303","DOI":"10.1097\/00003246-200107000-00002","article-title":"Epidemiology of severe sepsis in the United States: Analysis of incidence, 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