{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,18]],"date-time":"2026-03-18T10:13:29Z","timestamp":1773828809230,"version":"3.50.1"},"reference-count":51,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2026,3,4]],"date-time":"2026-03-04T00:00:00Z","timestamp":1772582400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,3,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Continuous infusion (CI) of linezolid has been proposed to stabilize exposure and improve pharmacokinetic\/pharmacodynamic (PK\/PD) target attainment compared with conventional intermittent dosing. By maintaining concentrations above inhibitory thresholds, CI may optimize antibacterial efficacy and reduce inter- and intra-patient variability. However, this \u2018new way of dosing\u2019 revisits \u2018old risks\u2019 associated with linezolid, including nonlinear PK, metabolic saturation, and concentration-dependent toxicities such as lactic acidosis, myelosuppression and neurotoxicity. Rather than eliminating these concerns, CI may accentuate them by prolonging exposure near toxic thresholds, particularly in patients with impaired elimination. Current evidence is predominantly PK; robust clinical outcome data remain limited. Our review synthesizes pharmacometric, observational and trial data and outlines how therapeutic drug monitoring and model-informed precision dosing can be used to individualize CI while surveilling for toxicity. We propose a pragmatic framework for candidate selection, regimen design aligned to PK\/PD goals, early therapeutic drug monitoring with adaptive adjustments and vigilant safety monitoring. Overall, CI of linezolid is mechanistically attractive but is not established as standard of care; its use should remain individualized, safety-conscious and evidence-generating pending randomized controlled trials.<\/jats:p>","DOI":"10.1093\/jac\/dkag100","type":"journal-article","created":{"date-parts":[[2026,3,18]],"date-time":"2026-03-18T07:56:02Z","timestamp":1773820562000},"source":"Crossref","is-referenced-by-count":0,"title":["Continuous linezolid infusion: the new way to dose, the old risks to fear"],"prefix":"10.1093","volume":"81","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8667-8159","authenticated-orcid":false,"given":"Daniel","family":"Mu\u00f1oz-Pichuante","sequence":"first","affiliation":[{"name":"Universidad San Sebasti\u00e1n Escuela de Qu\u00edmica y Farmacia, Facultad de Ciencias, , Valdivia ,","place":["Chile"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jaime","family":"Sasso","sequence":"additional","affiliation":[{"name":"Universidad San Sebasti\u00e1n Escuela de Qu\u00edmica y Farmacia, Facultad de Ciencias, , Santiago ,","place":["Chile"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7183-6372","authenticated-orcid":false,"given":"Ricardo","family":"Nalda-Molina","sequence":"additional","affiliation":[{"name":"Miguel Hernandez University Pharmacy and Pharmaceutics Division, Department of Engineering, , San Juan de Alicante, Alicante ,","place":["Spain"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amelia","family":"Ramon-Lopez","sequence":"additional","affiliation":[{"name":"Miguel Hernandez University Pharmacy and Pharmaceutics Division, Department of Engineering, , San Juan de Alicante, Alicante ,","place":["Spain"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lorenzo","family":"Villa-Zapata","sequence":"additional","affiliation":[{"name":"Clinical and Administrative Pharmacy University of Georgia College of Pharmacy , Athens, GA ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2026,3,18]]},"reference":[{"key":"2026031803555552400_dkag100-B1","doi-asserted-by":"publisher","first-page":"1759","DOI":"10.2147\/DDDT.S164515","article-title":"Linezolid: a review of its properties, function, and use in critical care","volume":"12","author":"Hashemian","year":"2018","journal-title":"Drug Des Devel Ther"},{"key":"2026031803555552400_dkag100-B2","doi-asserted-by":"publisher","first-page":"493","DOI":"10.21037\/atm.2020.03.207","article-title":"Does the conventional dosage of linezolid necessitate therapeutic drug monitoring?\u2014experience from a prospective observational study","volume":"8","author":"Fang","year":"2020","journal-title":"Ann Transl Med"},{"key":"2026031803555552400_dkag100-B3","doi-asserted-by":"publisher","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":"2026031803555552400_dkag100-B4","doi-asserted-by":"publisher","first-page":"209","DOI":"10.1007\/s40262-023-01213-x","article-title":"Pharmacokinetic alterations associated with critical illness","volume":"62","author":"Morales Castro","year":"2023","journal-title":"Clin Pharmacokinet"},{"key":"2026031803555552400_dkag100-B5","doi-asserted-by":"publisher","first-page":"119","DOI":"10.1186\/s13054-017-1696-z","article-title":"Timing of appropriate empirical antimicrobial administration and outcome of adults with community-onset bacteremia","volume":"21","author":"Lee","year":"2017","journal-title":"Crit Care"},{"key":"2026031803555552400_dkag100-B6","doi-asserted-by":"publisher","first-page":"1301","DOI":"10.1007\/s00228-022-03340-z","article-title":"Applying pharmacokinetic\/pharmacodynamic measurements for linezolid in critically ill patients: optimizing efficacy and reducing resistance occurrence","volume":"78","author":"El-Gaml","year":"2022","journal-title":"Eur J Clin Pharmacol"},{"key":"2026031803555552400_dkag100-B7","doi-asserted-by":"publisher","first-page":"1118","DOI":"10.5005\/jp-journals-10071-24848","article-title":"Efficacy and safety of continuous vs intermittent linezolid infusion in critically ill patients with septic shock","volume":"28","author":"Albadry","year":"2024","journal-title":"Indian J Crit Care Med"},{"key":"2026031803555552400_dkag100-B8","doi-asserted-by":"publisher","first-page":"1287","DOI":"10.1128\/AAC.01194-06","article-title":"Pharmacokinetic\/pharmacodynamic factors influencing emergence of resistance to linezolid in an in vitro model","volume":"51","author":"Boak","year":"2007","journal-title":"Antimicrob Agents Chemother"},{"key":"2026031803555552400_dkag100-B9","doi-asserted-by":"publisher","first-page":"259","DOI":"10.1016\/j.ijantimicag.2016.05.009","article-title":"Pharmacokinetic\/pharmacodynamic evaluation of linezolid for the treatment of staphylococcal infections in critically ill patients","volume":"48","author":"Dong","year":"2016","journal-title":"Int J Antimicrob Agents"},{"key":"2026031803555552400_dkag100-B10","doi-asserted-by":"publisher","first-page":"39","DOI":"10.2217\/fmb-2016-0140","article-title":"Optimization of linezolid treatment regimens for gram-positive bacterial infections based on pharmacokinetic\/pharmacodynamic analysis","volume":"12","author":"Yang","year":"2017","journal-title":"Future Microbiol"},{"key":"2026031803555552400_dkag100-B11","doi-asserted-by":"publisher","first-page":"1129","DOI":"10.2165\/00003088-200342130-00004","article-title":"Clinical pharmacokinetics of linezolid, a novel oxazolidinone antibacterial","volume":"42","author":"Stalker","year":"2003","journal-title":"Clin Pharmacokinet"},{"key":"2026031803555552400_dkag100-B12","doi-asserted-by":"publisher","first-page":"1816","DOI":"10.1124\/dmd.106.013755","article-title":"Does linezolid inhibit its own metabolism? Population pharmacokinetics as a tool to explain the observed nonlinearity in both healthy volunteers and septic patients","volume":"35","author":"Plock","year":"2007","journal-title":"Drug Metab Dispos"},{"key":"2026031803555552400_dkag100-B13","doi-asserted-by":"publisher","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":"2026031803555552400_dkag100-B14","doi-asserted-by":"publisher","first-page":"1157","DOI":"10.1007\/s00134-025-07889-y","article-title":"Continuous infusion of linezolid for critically ill patients: toward a new standard of care","volume":"51","author":"Barrasa","year":"2025","journal-title":"Intensive Care Med"},{"key":"2026031803555552400_dkag100-B15","doi-asserted-by":"publisher","first-page":"54","DOI":"10.3390\/pharmaceutics12010054","article-title":"Novel population pharmacokinetic model for linezolid in critically ill patients and evaluation of the adequacy of the current dosing recommendation","volume":"12","author":"Soraluce","year":"2020","journal-title":"Pharmaceutics"},{"key":"2026031803555552400_dkag100-B16","doi-asserted-by":"publisher","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":"2026031803555552400_dkag100-B17","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":"2026031803555552400_dkag100-B18","doi-asserted-by":"publisher","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":"2026031803555552400_dkag100-B19","doi-asserted-by":"publisher","first-page":"296","DOI":"10.3390\/ph15030296","article-title":"Continuous versus intermittent linezolid infusion for critically ill patients with hospital-acquired and ventilator-associated pneumonia: efficacy and safety challenges","volume":"15","author":"Abou Warda","year":"2022","journal-title":"Pharmaceuticals (Basel)"},{"key":"2026031803555552400_dkag100-B20","doi-asserted-by":"publisher","first-page":"e02490-20","DOI":"10.1128\/AAC.02490-20","article-title":"Dosage individualization of linezolid: precision dosing of linezolid to optimize efficacy and minimize toxicity","volume":"65","author":"Luque","year":"2021","journal-title":"Antimicrob Agents Chemother"},{"key":"2026031803555552400_dkag100-B21","doi-asserted-by":"publisher","first-page":"967311","DOI":"10.3389\/fpubh.2022.967311","article-title":"Expert consensus statement on therapeutic drug monitoring and individualization of linezolid","volume":"10","author":"Lin","year":"2022","journal-title":"Front Public Health"},{"key":"2026031803555552400_dkag100-B22","doi-asserted-by":"publisher","first-page":"3100","DOI":"10.1093\/jac\/dkx249","article-title":"Testing the mutant selection window hypothesis with Staphylococcus aureus exposed to linezolid in an in vitro dynamic model","volume":"72","author":"Firsov","year":"2017","journal-title":"J Antimicrob Chemother"},{"key":"2026031803555552400_dkag100-B23","doi-asserted-by":"publisher","first-page":"514","DOI":"10.1038\/s41429-017-0016-9","article-title":"Time inside the mutant selection window as a predictor of staphylococcal resistance to linezolid","volume":"71","author":"Alieva","year":"2018","journal-title":"J Antibiot (Tokyo)"},{"key":"2026031803555552400_dkag100-B24","doi-asserted-by":"publisher","first-page":"e01373-22","DOI":"10.1128\/aac.01373-22","article-title":"Mutant prevention concentration, frequency of spontaneous mutant selection, and mutant selection window\u2014a new approach to the in vitro determination of the antimicrobial potency of compounds","volume":"67","author":"Krajewska","year":"2023","journal-title":"Antimicrob Agents Chemother"},{"key":"2026031803555552400_dkag100-B25","doi-asserted-by":"publisher","first-page":"4","DOI":"10.1038\/s41429-024-00778-4","article-title":"Resistance to linezolid in Staphylococcus aureus by mutation, modification, and acquisition of genes","volume":"78","author":"Yang","year":"2025","journal-title":"J Antibiot (Tokyo)"},{"key":"2026031803555552400_dkag100-B26","doi-asserted-by":"publisher","first-page":"e1299","DOI":"10.1097\/CCE.0000000000001299","article-title":"Impact of extending beta-lactam infusions on IV access requirements","volume":"7","author":"Kooda","year":"2025","journal-title":"Crit Care Explor"},{"key":"2026031803555552400_dkag100-B27","doi-asserted-by":"publisher","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":"2026031803555552400_dkag100-B28","doi-asserted-by":"publisher","first-page":"436","DOI":"10.3390\/antibiotics11040436","article-title":"Linezolid administration to critically ill patients: intermittent or continuous infusion? A systematic literature search and review","volume":"11","author":"Hui","year":"2022","journal-title":"Antibiotics (Basel)"},{"key":"2026031803555552400_dkag100-B29","doi-asserted-by":"publisher","first-page":"789","DOI":"10.1007\/s40262-022-01125-2","article-title":"A review of population pharmacokinetic analyses of linezolid","volume":"61","author":"Band\u00edn-Vilar","year":"2022","journal-title":"Clin Pharmacokinet"},{"key":"2026031803555552400_dkag100-B30","doi-asserted-by":"publisher","first-page":"106881","DOI":"10.1016\/j.ijantimicag.2023.106881","article-title":"Dose optimisation of linezolid in critically ill patients based on a population pharmacokinetic model: a two-centre prospective interventional study","volume":"62","author":"Shi","year":"2023","journal-title":"Int J Antimicrob Agents"},{"key":"2026031803555552400_dkag100-B31","doi-asserted-by":"publisher","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":"2026031803555552400_dkag100-B32","doi-asserted-by":"publisher","first-page":"e2418234","DOI":"10.1001\/jamanetworkopen.2024.18234","article-title":"Extended-infusion \u03b2-lactam therapy, mortality, and subsequent antibiotic resistance among hospitalized adults with Gram-negative bloodstream infections","volume":"7","author":"Karaba","year":"2024","journal-title":"JAMA Netw Open"},{"key":"2026031803555552400_dkag100-B33","doi-asserted-by":"publisher","first-page":"533","DOI":"10.1517\/17425255.2016.1166204","article-title":"Drug monitoring and individual dose optimization of antimicrobial drugs: oxazolidinones","volume":"12","author":"Cattaneo","year":"2016","journal-title":"Expert Opin Drug Metab Toxicol"},{"key":"2026031803555552400_dkag100-B34","doi-asserted-by":"publisher","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":"2026031803555552400_dkag100-B35","doi-asserted-by":"publisher","first-page":"1200","DOI":"10.1093\/infdis\/jiad413","article-title":"Linezolid population pharmacokinetic model in plasma and cerebrospinal fluid among patients with tuberculosis meningitis","volume":"229","author":"Abdelgawad","year":"2024","journal-title":"J Infect Dis"},{"key":"2026031803555552400_dkag100-B36","doi-asserted-by":"publisher","first-page":"1173","DOI":"10.1093\/cid\/ciac917","article-title":"Linezolid population pharmacokinetics to improve dosing in cardiosurgical patients: factoring a new drug\u2013drug interaction pathway","volume":"76","author":"Pai","year":"2023","journal-title":"Clin Infect Dis"},{"key":"2026031803555552400_dkag100-B37","doi-asserted-by":"publisher","first-page":"1111","DOI":"10.1086\/501356","article-title":"Linezolid-induced inhibition of mitochondrial protein synthesis","volume":"42","author":"De Vriese","year":"2006","journal-title":"Clin Infect Dis"},{"key":"2026031803555552400_dkag100-B38","doi-asserted-by":"publisher","first-page":"e579","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":"2026031803555552400_dkag100-B39","doi-asserted-by":"publisher","first-page":"e113","DOI":"10.1086\/430441","article-title":"Does linezolid cause lactic acidosis by inhibiting mitochondrial protein synthesis?","volume":"40","author":"Palenzuela","year":"2005","journal-title":"Clin Infect Dis"},{"key":"2026031803555552400_dkag100-B40","doi-asserted-by":"publisher","first-page":"962","DOI":"10.1128\/AAC.01190-06","article-title":"Reversible inhibition of mitochondrial protein synthesis during linezolid-related hyperlactatemia","volume":"51","author":"Garrabou","year":"2007","journal-title":"Antimicrob Agents Chemother"},{"key":"2026031803555552400_dkag100-B41","doi-asserted-by":"publisher","first-page":"547","DOI":"10.1002\/9781119329725.ch36","volume-title":"Mitochondrial Toxicity: Methods and Protocols","author":"Santini","year":"2018"},{"key":"2026031803555552400_dkag100-B42","doi-asserted-by":"publisher","first-page":"557","DOI":"10.1016\/j.ijantimicag.2017.06.023","article-title":"Linezolid in liver failure: exploring the value of the maximal liver function capacity (LiMAx) test in a pharmacokinetic pilot study","volume":"50","author":"Wicha","year":"2017","journal-title":"Int J Antimicrob Agents"},{"key":"2026031803555552400_dkag100-B43","doi-asserted-by":"publisher","first-page":"291","DOI":"10.1007\/s00228-009-0766-9","article-title":"Pharmacokinetics of linezolid in septic patients with and without extended dialysis","volume":"66","author":"Swoboda","year":"2010","journal-title":"Eur J Clin Pharmacol"},{"key":"2026031803555552400_dkag100-B44","doi-asserted-by":"publisher","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":"2026031803555552400_dkag100-B45","doi-asserted-by":"publisher","first-page":"3588","DOI":"10.1093\/jac\/dkz374","article-title":"Proactive therapeutic drug monitoring (TDM) may be helpful in managing long-term treatment with linezolid safely: findings from a monocentric, prospective, open-label, interventional study","volume":"74","author":"Cojutti","year":"2019","journal-title":"J Antimicrob Chemother"},{"key":"2026031803555552400_dkag100-B46","doi-asserted-by":"publisher","first-page":"89","DOI":"10.1186\/s40360-022-00628-9","article-title":"Safety of linezolid in patients with decreased renal function and trough monitoring: a systematic review and meta-analysis","volume":"23","author":"Liu","year":"2022","journal-title":"BMC Pharmacol Toxicol"},{"key":"2026031803555552400_dkag100-B47","doi-asserted-by":"publisher","first-page":"833","DOI":"10.1080\/14740338.2017.1335305","article-title":"Linezolid-induced lactic acidosis: the thin line between bacterial and mitochondrial ribosomes","volume":"16","author":"Santini","year":"2017","journal-title":"Expert Opin Drug Saf"},{"key":"2026031803555552400_dkag100-B48","doi-asserted-by":"publisher","first-page":"e00133-20","DOI":"10.1128\/AAC.00133-20","article-title":"Population pharmacokinetics and dosage optimization of linezolid in patients with liver dysfunction","volume":"64","author":"Zhang","year":"2020","journal-title":"Antimicrob Agents Chemother"},{"key":"2026031803555552400_dkag100-B49","doi-asserted-by":"publisher","first-page":"2362","DOI":"10.1097\/TP.0000000000003691","article-title":"Mitochondrial dysfunction and oxidative stress in liver transplantation and underlying diseases: new insights and therapeutics","volume":"105","author":"Shi","year":"2021","journal-title":"Transplantation"},{"key":"2026031803555552400_dkag100-B50","doi-asserted-by":"publisher","first-page":"e0053324","DOI":"10.1128\/aac.00533-24","article-title":"Oxazolidinone antibiotics impair ex vivo megakaryocyte differentiation from hematopoietic progenitor cells and their maturation into platelets","volume":"68","author":"Milosevic","year":"2024","journal-title":"Antimicrob Agents Chemother"},{"key":"2026031803555552400_dkag100-B51","doi-asserted-by":"publisher","first-page":"661","DOI":"10.1016\/j.ijantimicag.2019.07.021","article-title":"Prolonged inhibition and incomplete recovery of mitochondrial function in oxazolidinone-treated megakaryoblastic cell lines","volume":"54","author":"Milosevic","year":"2019","journal-title":"Int J Antimicrob Agents"}],"container-title":["Journal of Antimicrobial Chemotherapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/jac\/article-pdf\/81\/4\/dkag100\/67386024\/dkag100.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jac\/article-pdf\/81\/4\/dkag100\/67386024\/dkag100.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,18]],"date-time":"2026-03-18T07:56:03Z","timestamp":1773820563000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jac\/article\/doi\/10.1093\/jac\/dkag100\/8527039"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3,4]]},"references-count":51,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2026,3,4]]}},"URL":"https:\/\/doi.org\/10.1093\/jac\/dkag100","relation":{},"ISSN":["0305-7453","1460-2091"],"issn-type":[{"value":"0305-7453","type":"print"},{"value":"1460-2091","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2026,4]]},"published":{"date-parts":[[2026,3,4]]},"article-number":"dkag100"}}