{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,5]],"date-time":"2026-09-05T11:30:40Z","timestamp":1788607840780,"version":"build-2803163510"},"reference-count":32,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2025,11,21]],"date-time":"2025-11-21T00:00:00Z","timestamp":1763683200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antibiotics"],"abstract":"<jats:p>Background: Linezolid standard dosing is typically applied in ICU without adjustments, even in renal impairment. This study examines serum concentration variability by renal function or CRRT administration in patients receiving 1200 mg\/day of linezolid. Methods: This retrospective, single-center, non-randomized observational study was conducted at Niguarda Hospital (Milan, Italy) on data from the two-year period 2023\u20132024. ICU patients receiving linezolid, with a renal function determination and trough TDM performed at steady-state were included and stratified by renal function or CRRT status. Results: 54 patients were included, with 18 (33%) undergoing CRRT (CVVH). CRRT patients presented higher median linezolid concentrations (4.6 mg\/L) than non-CRRT patients (3.2 mg\/L), and a lower risk of underdosing (17% vs. 39%). CRRT patients showed significantly lower concentrations (4.6 mg\/L vs. 10 mg\/L, p = 0.007) than non-CRRT patients with renal function \u2264 30 mL\/min, with fewer out-of-range levels (39% vs. 91%, p = 0.008) and overdosing (22% vs. 73%, p = 0.018). A significant inverse correlation was found between renal function and linezolid levels (Spearman\u2019s rho = \u22120.61, p &lt; 0.001), with CRRT patients exhibiting concentrations comparable to those of individuals with moderately impaired renal function. Continuous infusion resulted in significantly higher median concentrations (7.2 mg\/L) than extended infusion (2.7 mg\/L), with an increased risk of overdosing (47% vs. 17%; p = 0.018). Conclusions: After standard-dosing administration, linezolid levels vary widely in critically ill patients. Renal function significantly affects pharmacokinetics: severe impairment increases overdose risk, while ARC may cause underdosing. Standard-dosing appears adequate in CRRT patients, with levels similar to moderate-impairment. Continuous infusion aids target attainment in normal or ARC patients but raises overdose risk in severe impairment. TDM-based personalized dosing seems crucial to optimize therapy and reduce toxicity or failure.<\/jats:p>","DOI":"10.3390\/antibiotics14121188","type":"journal-article","created":{"date-parts":[[2025,11,21]],"date-time":"2025-11-21T14:17:23Z","timestamp":1763734643000},"page":"1188","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Linezolid Serum Concentration Variability Among Critically Ill Patients Based on Renal Function and Continuous Renal Replacement Therapy Administration"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9765-5529","authenticated-orcid":false,"given":"Stefano","family":"Agliardi","sequence":"first","affiliation":[{"name":"Department of Medical Biotechnologies and Translational Medicine, Post-Graduate School of Pharmacology and Clinical Toxicology, University of Milan, 20122 Milan, Italy"},{"name":"Chemical-Clinical Analyses, Poison Control Center and Clinical Pharmacology Unit, ASST Grande Ospedale Metropolitano Niguarda, 20162 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-3110-5967","authenticated-orcid":false,"given":"Beatrice","family":"Brunoni","sequence":"additional","affiliation":[{"name":"Department of Medicine and Surgery, University of Milano-Bicocca, 20126 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0648-3309","authenticated-orcid":false,"given":"Gianluca","family":"Gazzaniga","sequence":"additional","affiliation":[{"name":"Department of Medical Biotechnologies and Translational Medicine, Post-Graduate School of Pharmacology and Clinical Toxicology, University of Milan, 20122 Milan, Italy"},{"name":"Department of General Surgery, Surgical Specialty and Anesthesiology Paride Stefanini, Sapienza University of Rome, 00161 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-3993-0381","authenticated-orcid":false,"given":"Leonardo","family":"Baggio","sequence":"additional","affiliation":[{"name":"Department of Medicine and Surgery, University of Milano-Bicocca, 20126 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Riccardo","family":"Giossi","sequence":"additional","affiliation":[{"name":"Chemical-Clinical Analyses, Poison Control Center and Clinical Pharmacology Unit, ASST Grande Ospedale Metropolitano Niguarda, 20162 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-4589-017X","authenticated-orcid":false,"given":"Greta","family":"Guarnieri","sequence":"additional","affiliation":[{"name":"Department of Medical Biotechnologies and Translational Medicine, Post-Graduate School of Pharmacology and Clinical Toxicology, University of Milan, 20122 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefania","family":"Paccagnini","sequence":"additional","affiliation":[{"name":"Chemical-Clinical Analyses, Poison Control Center and Clinical Pharmacology Unit, ASST Grande Ospedale Metropolitano Niguarda, 20162 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matteo","family":"Laratta","sequence":"additional","affiliation":[{"name":"Department of Anesthesia and Intensive Care Medicine, ASST Grande Ospedale Metropolitano Niguarda, 20162 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Langer","sequence":"additional","affiliation":[{"name":"Department of Medicine and Surgery, University of Milano-Bicocca, 20126 Milan, Italy"},{"name":"Department of Anesthesia and Intensive Care Medicine, ASST Grande Ospedale Metropolitano Niguarda, 20162 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Santambrogio","sequence":"additional","affiliation":[{"name":"Department of Anesthesia and Intensive Care Medicine, ASST Grande Ospedale Metropolitano Niguarda, 20162 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gianpaola","family":"Monti","sequence":"additional","affiliation":[{"name":"Department of Anesthesia and Intensive Care Medicine, ASST Grande Ospedale Metropolitano Niguarda, 20162 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Romano","family":"Danesi","sequence":"additional","affiliation":[{"name":"Chemical-Clinical Analyses, Poison Control Center and Clinical Pharmacology Unit, ASST Grande Ospedale Metropolitano Niguarda, 20162 Milan, Italy"},{"name":"Department of Oncology and Hemato-Oncology, Universit\u00e0 degli Studi di Milano, 20122 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8554-2401","authenticated-orcid":false,"given":"Francesco","family":"Scaglione","sequence":"additional","affiliation":[{"name":"Department of Oncology and Hemato-Oncology, Universit\u00e0 degli Studi di Milano, 20122 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6464-2596","authenticated-orcid":false,"given":"Arianna","family":"Pani","sequence":"additional","affiliation":[{"name":"Department of Oncology and Hemato-Oncology, Universit\u00e0 degli Studi di Milano, 20122 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0398-1329","authenticated-orcid":false,"given":"Roberto","family":"Fumagalli","sequence":"additional","affiliation":[{"name":"Department of Medicine and Surgery, University of Milano-Bicocca, 20126 Milan, Italy"},{"name":"Department of Anesthesia and Intensive Care Medicine, ASST Grande Ospedale Metropolitano Niguarda, 20162 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,11,21]]},"reference":[{"key":"ref_1","unstructured":"(2025, February 02). Zyvox (Linezolid) [Prescribing Information] Retrieved February 2025, Available online: https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/2014\/021130s032,021131s026,021132s031lbl.pdf."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1007\/s40262-023-01213-x","article-title":"Pharmacokinetic Alterations Associated with Critical Illness","volume":"62","author":"Castro","year":"2023","journal-title":"Clin. Pharmacokinet."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Fidalgo, P., and Bagshaw, S.M. (2014). Chronic Kidney Disease in the Intensive Care Unit. Management of Chronic Kidney Disease, Springer.","DOI":"10.1007\/978-3-642-54637-2_32"},{"key":"ref_4","doi-asserted-by":"crossref","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":"ref_5","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1016\/j.diagmicrobio.2015.01.013","article-title":"How can we ensure effective antibiotic dosing in critically ill patients receiving different types of renal replacement therapy?","volume":"82","author":"Jamal","year":"2015","journal-title":"Diagn. Microbiol. Infect. Dis."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1107","DOI":"10.1007\/s40262-018-0636-7","article-title":"Augmented Renal Clearance in Critically Ill Patients: A Systematic Review","volume":"57","author":"Barrasa","year":"2018","journal-title":"Clin. Pharmacokinet."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1097\/FTD.0000000000000942","article-title":"Therapeutic Drug Monitoring of Antibiotics in Critically Ill Patients: Current Practice and Future Perspectives with a Focus on Clinical Outcome","volume":"44","author":"Koch","year":"2022","journal-title":"Ther. Drug Monit."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1867","DOI":"10.1128\/AAC.01185-10","article-title":"Population pharmacokinetic and pharmacodynamic analysis of linezolid and a hematologic side effect, thrombocytopenia, in Japanese patients","volume":"55","author":"Sasaki","year":"2011","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"747","DOI":"10.1093\/ndt\/gfh707","article-title":"Assessment of renal function in recently admitted critically ill patients with normal serum creatinine","volume":"20","author":"Hoste","year":"2005","journal-title":"Nephrol. Dial. Transplant."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1007\/s00134-003-2078-3","article-title":"Defining acute renal failure: Physiological principles","volume":"30","author":"Bellomo","year":"2004","journal-title":"Intensive Care Med."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"R82","DOI":"10.1186\/cc9004","article-title":"Fluid accumulation, recognition and staging of acute kidney injury in critically-ill patients","volume":"14","author":"Macedo","year":"2010","journal-title":"Crit. Care Lond. Engl."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"R108","DOI":"10.1186\/cc12777","article-title":"Assessing glomerular filtration rate (GFR) in critically ill patients with acute kidney injury\u2014True GFR versus urinary creatinine clearance and estimating equations","volume":"17","author":"Bragadottir","year":"2013","journal-title":"Crit. Care Lond. Engl."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"e14540","DOI":"10.1111\/aas.14540","article-title":"Accuracy of estimating equations for the assessment of glomerular filtration rate in critically ill patients versus outpatients","volume":"69","author":"Kiss","year":"2025","journal-title":"Acta Anaesthesiol. Scand."},{"key":"ref_14","doi-asserted-by":"crossref","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":"Alffenaar","year":"2020","journal-title":"Intensive Care Med."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Corona, A., Veronese, A., Santini, S., and Cattaneo, D. (2022). \u201cCATCH\u201d Study: Correct Antibiotic Therapy in Continuous Hemofiltration in the Critically Ill in Continuous Renal Replacement Therapy: A Prospective Observational Study. Antibiotics, 11.","DOI":"10.3390\/antibiotics11121811"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"70","DOI":"10.2174\/1389200224666221228144117","article-title":"A Systematic Review of Linezolid Pharmacokinetics\/Pharmacodynamics in Patients Undergoing Continuous Renal Replacement Therapy: Does One Size Fit All?","volume":"24","author":"Liu","year":"2023","journal-title":"Curr. Drug Metab."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"374","DOI":"10.1186\/s13054-016-1551-7","article-title":"Effects of continuous renal replacement therapy on linezolid pharmacokinetic\/pharmacodynamics: A systematic review","volume":"20","author":"Villa","year":"2016","journal-title":"Crit. Care Lond. Engl."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"2204","DOI":"10.1002\/hep.30824","article-title":"Liver Injury and Failure in Critical Illness","volume":"70","author":"Horvatits","year":"2019","journal-title":"Hepatology"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1007\/s00228-022-03427-7","article-title":"A standard dose of linezolid puts patients with hepatic impairment at risk of overexposure","volume":"79","author":"Liao","year":"2023","journal-title":"Eur. J. Clin. Pharmacol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"229","DOI":"10.2147\/IJGM.S102819","article-title":"Human serum albumin homeostasis: A new look at the roles of synthesis, catabolism, renal and gastrointestinal excretion, and the clinical value of serum albumin measurements","volume":"9","author":"Levitt","year":"2016","journal-title":"Int. J. Gen. Med."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"99","DOI":"10.2165\/11539220-000000000-00000","article-title":"The effects of hypoalbuminaemia on optimizing antibacterial dosing in critically ill patients","volume":"50","author":"Ulldemolins","year":"2011","journal-title":"Clin. Pharmacokinet."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"2087","DOI":"10.2147\/DDDT.S136335","article-title":"Evaluation of the stability of linezolid in aqueous solution and commonly used intravenous fluids","volume":"11","author":"Taylor","year":"2017","journal-title":"Drug Des. Devel. Ther."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"740","DOI":"10.1002\/phar.2842","article-title":"International consensus recommendations for the use of prolonged-infusion beta-lactam antibiotics: Endorsed by the American College of Clinical Pharmacy, British Society for Antimicrobial Chemotherapy, Cystic Fibrosis Foundation, European Society of Clinical Microbiology and Infectious Diseases, Infectious Diseases Society of America, Society of Critical Care Medicine, and Society of Infectious Diseases Pharmacists","volume":"43","author":"Hong","year":"2023","journal-title":"Pharmacotherapy"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"835","DOI":"10.1093\/ajhp\/zxaa036","article-title":"Therapeutic monitoring of vancomycin for serious methicillin-resistant Staphylococcus aureus infections: A revised consensus guideline and review by the American Society of Health-System Pharmacists, the Infectious Diseases Society of America, the Pediatric Infectious Diseases Society, and the Society of Infectious Diseases Pharmacists","volume":"77","author":"Rybak","year":"2020","journal-title":"Am. J. Health-Syst. Pharm."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Warda, A.E.A., Sarhan, R.M., Al-Fishawy, H.S., Moharram, A.N., and Salem, H.F. (2022). Continuous Versus Intermittent Linezolid Infusion for Critically Ill Patients with Hospital-Acquired and Ventilator-Associated Pneumonia: Efficacy and Safety Challenges. Pharmaceuticals, 15.","DOI":"10.3390\/ph15030296"},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Hui, L.-A., Bodolea, C., Popa, A., Vlase, A.-M., Hiri\u0219c\u0103u, E.I., and Vlase, L. (2024). Linezolid Pharmacokinetics in Critically Ill Patients: Continuous Versus Intermittent Infusion. Antibiotics, 13.","DOI":"10.3390\/antibiotics13100961"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"106572","DOI":"10.1016\/j.ijantimicag.2022.106572","article-title":"Population pharmacokinetics and toxicodynamics of continuously infused linezolid in critically ill patients","volume":"59","author":"Wicha","year":"2022","journal-title":"Int. J. Antimicrob. Agents"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"4605","DOI":"10.1128\/AAC.00177-10","article-title":"Therapeutic drug monitoring of linezolid: A retrospective monocentric analysis","volume":"54","author":"Pea","year":"2010","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"2034","DOI":"10.1093\/jac\/dks153","article-title":"Therapeutic drug monitoring may improve safety outcomes of long-term treatment with linezolid in adult patients","volume":"67","author":"Pea","year":"2012","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1016\/j.diagmicrobio.2007.06.001","article-title":"Zyvox Annual Appraisal of Potency and Spectrum Program Results for 2006: An activity and spectrum analysis of linezolid using clinical isolates from 16 countries","volume":"59","author":"Jones","year":"2007","journal-title":"Diagn. Microbiol. Infect. Dis."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1016\/j.ijantimicag.2007.09.009","article-title":"Linezolid pharmacokinetic\/pharmacodynamic profile in critically ill septic patients: Intermittent versus continuous infusion","volume":"31","author":"Adembri","year":"2008","journal-title":"Int. J. Antimicrob. Agents"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1007\/s00134-014-3550-y","article-title":"Linezolid plasma and intrapulmonary concentrations in critically ill obese patients with ventilator-associated pneumonia: Intermittent vs continuous administration","volume":"41","author":"Fortuna","year":"2015","journal-title":"Intensive Care Med."}],"container-title":["Antibiotics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2079-6382\/14\/12\/1188\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,11,24]],"date-time":"2025-11-24T09:42:32Z","timestamp":1763977352000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2079-6382\/14\/12\/1188"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,11,21]]},"references-count":32,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2025,12]]}},"alternative-id":["antibiotics14121188"],"URL":"https:\/\/doi.org\/10.3390\/antibiotics14121188","relation":{},"ISSN":["2079-6382"],"issn-type":[{"value":"2079-6382","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,11,21]]}}}