{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T14:17:41Z","timestamp":1783606661087,"version":"3.55.0"},"reference-count":39,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2022,3,24]],"date-time":"2022-03-24T00:00:00Z","timestamp":1648080000000},"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>A judicious antibiotic therapy is one of the challenges in the therapy of critically ill patients with sepsis and septic shock. The pathophysiological changes in these patients significantly alter the antibiotic pharmacokinetics (PK) and pharmacodynamics (PD) with important consequences in reaching the therapeutic targets or the risk of side effects. The use of linezolid, an oxazolidinone antibiotic, in intensive care is such an example. The optimization of its therapeutic effects, administration in intermittent (II) or continuous infusion (CI) is gaining increased interest. In a systematic review of the main databases, we propose a detailed analysis of the main PK\/PD determinants, their relationship with the clinical therapeutic response and the occurrence of adverse effects following II or CI of linezolid to different classes of critically ill patients or in Monte Carlo simulations.<\/jats:p>","DOI":"10.3390\/antibiotics11040436","type":"journal-article","created":{"date-parts":[[2022,3,25]],"date-time":"2022-03-25T00:05:18Z","timestamp":1648166718000},"page":"436","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Linezolid Administration to Critically Ill Patients: Intermittent or Continuous Infusion? A Systematic Literature Search and Review"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4630-1434","authenticated-orcid":false,"given":"Ligia-Ancuta","family":"Hui","sequence":"first","affiliation":[{"name":"Pharmaceutical Technology and Biopharmaceutics Department, Faculty of Pharmacy, University of Medicine and Pharmacy \u201cIuliu Hatieganu\u201d, 400012 Cluj-Napoca, Romania"},{"name":"Clinical Pharmacy Specialist, University Clinical Municipal Hospital, 400139 Cluj-Napoca, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7798-0762","authenticated-orcid":false,"given":"Constantin","family":"Bodolea","sequence":"additional","affiliation":[{"name":"ICU Department, Faculty of Medicine, University of Medicine and Pharmacy \u201cIuliu Hatieganu\u201d, 400006 Cluj-Napoca, Romania"},{"name":"ICU Department, University Clinical Municipal Hospital, 400139 Cluj-Napoca, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0664-3387","authenticated-orcid":false,"given":"Laurian","family":"Vlase","sequence":"additional","affiliation":[{"name":"Pharmaceutical Technology and Biopharmaceutics Department, Faculty of Pharmacy, University of Medicine and Pharmacy \u201cIuliu Hatieganu\u201d, 400012 Cluj-Napoca, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisabeta Ioana","family":"Hiriscau","sequence":"additional","affiliation":[{"name":"ICU Department, University Clinical Municipal Hospital, 400139 Cluj-Napoca, Romania"},{"name":"Nursing Department, Faculty of Medicine, University of Medicine and Pharmacy \u201cIuliu Hatieganu\u201d, 400089 Cluj-Napoca, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adina","family":"Popa","sequence":"additional","affiliation":[{"name":"Clinical Pharmacy Department, Faculty of Pharmacy, University of Medicine and Pharmacy \u201cIuliu Hatieganu\u201d, 400012 Cluj-Napoca, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,3,24]]},"reference":[{"key":"ref_1","unstructured":"World Health Organization (WHO) (2020, September 21). Antimicrobial Resistance. Available online: https:\/\/www.who.int\/news-room\/fact-sheets\/detail\/antibiotic-resistance."},{"key":"ref_2","unstructured":"United States Center for Disease Control and Prevention (CDC) (2020, September 21). Biggest Threats and Data Resistance, Available online: https:\/\/www.cdc.gov\/drugresistance\/biggest-threats.html."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1111\/j.1749-6632.2011.06330.x","article-title":"The Oxazolidinones: Past, Present, and Future","volume":"1241","author":"Shaw","year":"2011","journal-title":"Ann. N. Y. Acad Sci."},{"key":"ref_4","unstructured":"Grayson, M.L., Cosgrove, S.E., Crowe, S., Hope, W., McCarthy, J.S., Mills, J., Mouton, J.W., and Peterson, D.L. (2012). Kucers\u2019 the Use of Antibiotics, CRC Press. [6th ed.]."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1080\/17425255.2020.1750597","article-title":"Pharmacokinetic and Pharmacodynamic Considerations in Antimicrobial Therapy for Sepsis","volume":"16","author":"Fujii","year":"2020","journal-title":"Expert Opin. Drug Metab. Toxicol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"2129","DOI":"10.2147\/DDDT.S303497","article-title":"Pharmacokinetics of Linezolid Dose Adjustment for Creatinine Clearance in Critically Ill Patients: A Multicenter, Prospective, Open-Label, Observational Study","volume":"15","author":"Wang","year":"2021","journal-title":"Drug Des. Dev. Ther."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"525","DOI":"10.1186\/s13054-014-0525-x","article-title":"Therapeutic Drug Monitoring: Linezolid Too?","volume":"18","author":"Richards","year":"2014","journal-title":"Crit. Care"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"755","DOI":"10.2165\/00003088-200645080-00001","article-title":"Antibacterial Dosing in Intensive Care","volume":"45","author":"Roberts","year":"2006","journal-title":"Clin. Pharmacokinet."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"595","DOI":"10.1517\/17425255.2016.1170807","article-title":"Pharmacokinetics of Linezolid in Critically Ill Patients","volume":"12","author":"Sazdanovic","year":"2016","journal-title":"Expert Opin. Drug Metab. Toxicol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"840","DOI":"10.1097\/CCM.0b013e3181961bff","article-title":"Pharmacokinetic Issues for Antibiotics in the Critically Ill Patient","volume":"37","author":"Roberts","year":"2009","journal-title":"Crit. Care Med."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1016\/j.ijid.2020.02.044","article-title":"Impact of Augmented Renal Clearance on the Pharmacokinetics of Linezolid: Advantages of Continuous Infusion from a Pharmacokinetic\/Pharmacodynamic Perspective","volume":"93","author":"Barrasa","year":"2020","journal-title":"Int. J. Infect. Dis."},{"key":"ref_12","doi-asserted-by":"crossref","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":"Metz","year":"2020","journal-title":"Crit. Care"},{"key":"ref_13","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."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Soraluce, A., Barrasa, H., As\u00edn-Prieto, E., S\u00e1nchez-Izquierdo, J.\u00c1., Maynar, J., Isla, A., and Rodr\u00edguez-Gasc\u00f3n, A. (2020). Novel Population Pharmacokinetic Model for Linezolid in Critically Ill Patients and Evaluation of the Adequacy of the Current Dosing Recommendation. Pharmaceutics, 12.","DOI":"10.3390\/pharmaceutics12010054"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"681","DOI":"10.1164\/rccm.201601-0024OC","article-title":"Continuous versus Intermittent \u03b2-Lactam Infusion in Severe Sepsis: A Meta-Analysis of Individual Patient Data from Randomized Trials","volume":"194","author":"Roberts","year":"2016","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_16","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_17","doi-asserted-by":"crossref","first-page":"1411","DOI":"10.2165\/00003088-200342150-00007","article-title":"Clinical Pharmacodynamics of Linezolid in Seriously Ill Patients Treated in a Compassionate Use Programme","volume":"42","author":"Rayner","year":"2003","journal-title":"Clin. Pharmacokinet."},{"key":"ref_18","first-page":"201","article-title":"Linezolid Continuous Infusion in Obese Patients with Nosocomial Pneumonia","volume":"39","author":"Fortuna","year":"2013","journal-title":"Intensive Care Med."},{"key":"ref_19","first-page":"58","article-title":"Continuous Infusion of Linezolid in Critically Ill Patients: Optimizing the Dosage Regimen through a PK\/PD Analysis. 37th International Symposium on Intensive Care and Emergency Medicine (Part 3 of 3)","volume":"21","author":"Barrasa","year":"2017","journal-title":"Crit. Care"},{"key":"ref_20","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_21","doi-asserted-by":"crossref","first-page":"679","DOI":"10.1093\/jac\/dkq506","article-title":"Linezolid for Endocarditis: A Case Series of 14 Patients","volume":"66","author":"Tascini","year":"2011","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1016\/j.medin.2016.04.006","article-title":"Successful Treatment of Panton\u2013Valentine Leukocidin-Positive Methicillin-Resistant Staphylococcus Aureus Pneumonia with High Doses of Linezolid Administered in Continuous Infusion","volume":"41","author":"Grau","year":"2017","journal-title":"Med. Intensiva (Engl. Ed.)"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1207","DOI":"10.1093\/jac\/dks022","article-title":"Alveolar Diffusion and Pharmacokinetics of Linezolid Administered in Continuous Infusion to Critically Ill Patients with Ventilator-Associated Pneumonia","volume":"67","author":"Boselli","year":"2012","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"503","DOI":"10.3947\/ic.2021.0034","article-title":"Optimization of Linezolid Dosing Regimens for Treatment of Vancomycin-Resistant Enterococci Infection","volume":"53","author":"Santimaleeworagun","year":"2021","journal-title":"Infect. Chemother."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"548","DOI":"10.1128\/AAC.47.2.548-553.2003","article-title":"Population Pharmacokinetics of Linezolid in Patients Treated in a Compassionate-Use Program","volume":"47","author":"Meagher","year":"2003","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1515\/labmed-2020-0052","article-title":"Personalized Antibiotic Therapy- A Rapid High Performance Liquid Chromatography-Tandem Mass Spectrometry Method for the Quantitation of Eight Antibiotics and Voriconazole for Patients in the Intensive Care Unit","volume":"44","author":"Georgi","year":"2020","journal-title":"J. Lab. Med."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"2304","DOI":"10.1093\/jac\/dkx149","article-title":"Optimization of Linezolid Therapy in the Critically Ill: The Effect of Adjusted Infusion Regimens","volume":"72","author":"Taubert","year":"2017","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"579","DOI":"10.1097\/CCM.0000000000001478","article-title":"Changes in Whole-Body Oxygen Consumption and Skeletal Muscle Mitochondria during Linezolid-Induced Lactic Acidosis","volume":"44","author":"Protti","year":"2016","journal-title":"Crit. Care Med."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"765","DOI":"10.5414\/CP202317","article-title":"Pharmacokinetic\/Pharmacodynamic Research on Three Different Infusion Time Regimens of Linezolid in Healthy Chinese Volunteers","volume":"53","author":"Cai","year":"2015","journal-title":"Int. J. Clin. Pharmacol. Ther."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1007\/s00228-020-02978-x","article-title":"Prolonged Infusion of Linezolid Is Associated with Improved Pharmacokinetic\/Pharmacodynamic (PK\/PD) Profiles in Patients with External Ventricular Drains","volume":"77","author":"Zhao","year":"2021","journal-title":"Eur. J. Clin. Pharmacol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1222","DOI":"10.1016\/j.cmi.2020.04.009","article-title":"Risk of Target Non-Attainment in Obese Compared to Non-Obese Patients in Calculated Linezolid Therapy","volume":"26","author":"Ehmann","year":"2020","journal-title":"Clin. Microbiol. Infect."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1016\/j.ijid.2020.03.054","article-title":"Dosage Regimen and Toxicity Risk Assessment of Linezolid in Sepsis Patients","volume":"96","author":"Dou","year":"2020","journal-title":"Int. J. Infect. Dis."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"732503","DOI":"10.3389\/fphar.2021.732503","article-title":"Model Based Identification of Linezolid Exposure\u2013Toxicity Thresholds in Hospitalized Patients","volume":"12","author":"Fang","year":"2021","journal-title":"Front. Pharmacol."},{"key":"ref_34","unstructured":"(2022, January 11). Linezolid Kabi-Product Resume. Available online: https:\/\/www.anm.ro\/_\/_RCP\/RCP_7392_12.02.15.pdf."},{"key":"ref_35","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. Dev. Ther."},{"key":"ref_36","unstructured":"(2021, May 05). Micromedex-Linezolid Administration, Y Site Incompatibilities. Available online: https:\/\/www-micromedexsolutions-com.am.e-nformation.ro\/micromedex2\/librarian\/CS\/D9D0C5\/ND_PR\/evidencexpert\/ND_P\/evidencexpert\/DUPLICATIONSHIELDSYNC\/078916\/ND_PG\/evidencexpert\/ND_B\/evidencexpert\/ND_AppProduct\/evidencexpert\/ND_T\/evidencexpert\/PFActionId\/evi."},{"key":"ref_37","unstructured":"(2021, May 05). Medscape-Linezolid Administration, Y Site Incompatibilities. Available online: https:\/\/reference.medscape.com\/drug\/zyvox-linezolid-342574#11."},{"key":"ref_38","unstructured":"Gilbert, D.N., Chambers, H.F., Eliopoulos, G.M., Pavia, A.T., Black, D., Freedman, D.O., Kim, K., Schwarts, B., Saag, M.S., and Sanford, J.C. (2019). The Sanford Guide to Antimicrobial Therapy 2019, Antimicrobial Therapy Inc."},{"key":"ref_39","unstructured":"(2019, August 02). Prolonged Infusions of Beta-Lactam Antibiotics. Available online: https:\/\/www.uptodate.com\/contents\/prolonged-infusions-of-beta-lactam-antibiotics?search=continuous%20infusion&source=search_result&selectedTitle=1~150&usage_type=default&display_rank=1#H42557378."}],"container-title":["Antibiotics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2079-6382\/11\/4\/436\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T22:42:18Z","timestamp":1760136138000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2079-6382\/11\/4\/436"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,3,24]]},"references-count":39,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2022,4]]}},"alternative-id":["antibiotics11040436"],"URL":"https:\/\/doi.org\/10.3390\/antibiotics11040436","relation":{},"ISSN":["2079-6382"],"issn-type":[{"value":"2079-6382","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,3,24]]}}}