View source for Linezolid

{{Short description|Antibiotic medication}}
{{Use dmy dates|date=December 2018}}
{{cs1 config|name-list-style=vanc|display-authors=6}}
{{Featured article}}
{{Infobox drug
| Verifiedfields = 
| Watchedfields = 
| verifiedrevid = 850189766
| image = Linezolid.svg
| image_class = skin-invert-image
| width             = 
| alt = Skeletal formula of linezolid
| image2 = Linezolid-from-xtal-2008-3D-balls.png
| width2            = 
| alt2              = 
| caption           =

<!-- Clinical data -->
| pronounce   = {{IPAc-en|l|ɪ|ˈ|n|ɛ|z|əl|ɪ|d|,_|-|ˈ|n|eɪ|z|-}}
| tradename = Zyvox, Zyvoxam, others<!-- no generics here, please! -->
| Drugs.com = {{drugs.com|monograph|linezolid}}
| MedlinePlus = a602004
| DailyMedID = Linezolid
| pregnancy_AU = B3
| pregnancy_AU_comment = <ref name="Drugs.com pregnancy">{{cite web | title=Linezolid (Zyvox) Use During Pregnancy | website=Drugs.com | date=16 April 2018 | url=https://www.drugs.com/pregnancy/linezolid.html | access-date=17 March 2020 | archive-date=17 March 2020 | archive-url=https://web.archive.org/web/20200317065515/https://www.drugs.com/pregnancy/linezolid.html | url-status=live }}</ref>
| pregnancy_category= 
| routes_of_administration = [[Intravenous therapy|Intravenous infusion]], [[by mouth]]
| class = [[Oxazolidinone]] antibiotic
| ATC_prefix = J01
| ATC_suffix = XX08
| ATC_supplemental  =

<!-- Legal status -->
| legal_AU = S4
| legal_AU_comment = <ref>{{cite web | title=Linezolid, injection, 600 mg per 300 mL, tablet, 600 mg and powder for oral suspension, 20 mg per mL, Zyvox® | publisher=Australian Government Department of Health and Aged Care | date=24 September 2001 | url=https://www.pbs.gov.au/info/industry/listing/elements/pbac-meetings/psd/2013-07/linezolid | access-date=30 March 2024 | archive-date=18 November 2022 | archive-url=https://web.archive.org/web/20221118203806/https://www.pbs.gov.au/info/industry/listing/elements/pbac-meetings/psd/2013-07/linezolid | url-status=live }}</ref><ref>{{cite web | title=Public Summary | url=https://www.ebs.tga.gov.au/servlet/xmlmillr6?dbid=ebs/PublicHTML/pdfStore.nsf&docid=277696&agid=(PrintDetailsPublic)&actionid=1 | format=PDF | access-date=30 March 2024}}</ref><ref>{{cite web | title=Prescription medicines: registration of new generic medicines and biosimilar medicines, 2017 | website=Therapeutic Goods Administration (TGA) | date=21 June 2022 | url=https://www.tga.gov.au/resources/publication/publications/prescription-medicines-registration-new-generic-medicines-and-biosimilar-medicines-2017 | access-date=30 March 2024 | archive-date=6 July 2023 | archive-url=https://web.archive.org/web/20230706023149/https://www.tga.gov.au/resources/publication/publications/prescription-medicines-registration-new-generic-medicines-and-biosimilar-medicines-2017 | url-status=live }}</ref>
| legal_BR =  <!-- OTC, A1, A2, A3, B1, B2, C1, C2, C3, C4, C5, D1, D2, E, F -->
| legal_BR_comment = 
| legal_CA = Rx-only
| legal_CA_comment = <ref>{{cite web | title=Product information | website=health-products.canada.ca | date=31 July 2020 | url=https://health-products.canada.ca/dpd-bdpp/info?lang=eng&code=67614 | access-date=29 March 2024 | archive-date=29 March 2024 | archive-url=https://web.archive.org/web/20240329202900/https://health-products.canada.ca/dpd-bdpp/info?lang=eng&code=67614 | url-status=live }}</ref><ref>{{cite web | title=Product information | website=health-products.canada.ca | date=7 February 2006 | url=https://health-products.canada.ca/dpd-bdpp/info?lang=eng&code=67615 | access-date=29 March 2024 | archive-date=29 March 2024 | archive-url=https://web.archive.org/web/20240329203402/https://health-products.canada.ca/dpd-bdpp/info?lang=eng&code=67615 | url-status=live }}</ref>
| legal_DE = <!-- Anlage I, II, III or Unscheduled -->
| legal_DE_comment = 
| legal_NZ = <!-- Class A, B, C -->
| legal_NZ_comment = 
| legal_UK = POM
| legal_UK_comment = <ref name="Zyvox SPC" />
| legal_US = Rx-only
| legal_US_comment = <ref name="Zyvox FDA label" />
| legal_UN = <!-- N I, II, III, IV / P I, II, III, IV -->
| legal_UN_comment = 
| legal_status      = <!-- For countries not listed above -->

<!-- Pharmacokinetic data -->
| bioavailability = ~100% (oral)
| protein_bound = Low (31%)
| metabolism = [[Liver]] (50–70%, [[cytochrome P450|CYP]] not&nbsp;involved)
| metabolites       = 
| onset             = 
| elimination_half-life = 3–7&nbsp;hours;<ref name=Roger2018 /> longer half-life in [[Cerebrospinal fluid|CSF]] than [[blood plasma|plasma]]<ref name=Roger2018 />
| duration_of_action = 
| excretion = non-kidney, [[kidney]], and fecal<ref name=AHFS2016/>

<!-- Identifiers -->
| CAS_number_Ref = {{cascite|correct|??}}
| CAS_number = 165800-03-3
| CAS_supplemental  = 
| PubChem = 441401
| IUPHAR_ligand     = 
| DrugBank_Ref = {{drugbankcite|correct|drugbank}}
| DrugBank = DB00601
| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
| ChemSpiderID = 390139
| UNII_Ref = {{fdacite|correct|FDA}}
| UNII = ISQ9I6J12J
| KEGG_Ref = {{keggcite|correct|kegg}}
| KEGG = D00947
| ChEBI_Ref         = 
| ChEBI             = 63607
| ChEMBL_Ref = {{ebicite|correct|EBI}}
| ChEMBL = 126
| NIAID_ChemDB = 070944
| PDB_ligand        = ZLD
| synonyms          =

<!-- Chemical and physical data -->
| IUPAC_name = (''S'')-''N''-({3-[3-fluoro-4-(morpholin-4-yl)phenyl]-2-oxo-1,3-oxazolidin-5-yl}methyl)acetamide
| C=16 | H=20 | F=1 | N=3 | O=4
| SMILES = O=C1O[C@@H](CNC(=O)C)CN1c3cc(F)c(N2CCOCC2)cc3
| StdInChI_Ref = {{stdinchicite|correct|chemspider}}
| StdInChI = 1S/C16H20FN3O4/c1-11(21)18-9-13-10-20(16(22)24-13)12-2-3-15(14(17)8-12)19-4-6-23-7-5-19/h2-3,8,13H,4-7,9-10H2,1H3,(H,18,21)/t13-/m0/s1
| StdInChI_comment  = 
| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}
| StdInChIKey = TYZROVQLWOKYKF-ZDUSSCGKSA-N
| density           = 
| density_notes     = 
| melting_point     = 
| melting_high      = 
| melting_notes     = 
| boiling_point     = 
| boiling_notes     = 
| solubility        = 
| sol_units         = 
| specific_rotation = 
}}

<!-- Definition and uses -->
'''Linezolid''' is an [[antibiotic]] used for the treatment of [[infection]]s caused by [[Gram-positive bacteria]] that are [[antibiotic resistance|resistant]] to other antibiotics.<ref name=Roger2018>{{cite journal | vauthors = Roger C, Roberts JA, Muller L | title = Clinical Pharmacokinetics and Pharmacodynamics of Oxazolidinones | journal = Clinical Pharmacokinetics | volume = 57 | issue = 5 | pages = 559–575 | date = May 2018 | pmid = 29063519 | doi = 10.1007/s40262-017-0601-x | s2cid = 4961324 | doi-access = free }}</ref><ref name=AHFS2016/> Linezolid is active against most Gram-positive bacteria that cause disease, including [[Streptococcus|streptococci]], [[vancomycin-resistant enterococcus|vancomycin-resistant enterococci]] (VRE), and [[methicillin-resistant Staphylococcus aureus|methicillin-resistant ''Staphylococcus aureus'']] (MRSA).<ref name=Roger2018 /><ref name="Zyvox FDA label">{{cite web | title=Zyvox- linezolid injection, solution Zyvox- linezolid tablet, film coated Zyvox- linezolid suspension | website=DailyMed | date=21 February 2020 | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=6e70e63b-bfd5-478d-a8ee-8ba22c9efabd | access-date=17 March 2020 | archive-date=26 April 2021 | archive-url=https://web.archive.org/web/20210426030640/https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=6e70e63b-bfd5-478d-a8ee-8ba22c9efabd | url-status=live }}</ref> The main uses are infections of the [[skin]] and [[pneumonia]] although it may be used for a variety of other infections including [[drug-resistant tuberculosis]].<ref name=AHFS2016/><ref name=WHO2015Use>{{cite book | vauthors = ((World Health Organization)) | year = 2015 | title = The selection and use of essential medicines. Twentieth report of the WHO Expert Committee 2015 (including 19th WHO Model List of Essential Medicines and 5th WHO Model List of Essential Medicines for Children) | publisher = World Health Organization | location = Geneva | author-link = World Health Organization | hdl = 10665/189763 | id = WHO technical report series;994 | hdl-access=free | isbn = 9789241209946 | issn = 0512-3054 | pages=26–33 }}</ref> It is used either by [[intravenous|injection into a vein]] or [[by mouth]].<ref name=AHFS2016/>

<!-- Side effects -->
When given for short periods, linezolid is a relatively safe antibiotic.<ref name=Marino2007>{{cite book |vauthors=Marino PL, Sutin KM |chapter=Antimicrobial therapy |title=The ICU book |publisher=Lippincott Williams & Wilkins |location=Hagerstown, MD |year=2007 |page=817 |isbn=978-0-7817-4802-5}}</ref> It can be used in people of all ages and in people with [[liver disease]] or [[renal failure|poor kidney function]].<ref name=AHFS2016/> Common side effects with short-term use include [[headache]], [[diarrhea]], rash, and [[nausea]].<ref name=AHFS2016/> Serious side effects may include [[serotonin syndrome]], [[bone marrow suppression]], and [[lactic acidosis|high blood lactate levels]], particularly when used for more than two weeks.<ref name=AHFS2016/><ref name=SFX2016/> If used for longer periods it may cause  [[chemotherapy-induced peripheral neuropathy|nerve damage]], including [[optic neuropathy|optic nerve damage]], which may be irreversible.<ref name=SFX2016>{{cite web|title=Linezolid Side Effects in Detail|url=https://www.drugs.com/sfx/linezolid-side-effects.html|website=drugs.com|access-date=11 December 2016|url-status=live|archive-url=https://web.archive.org/web/20161220233415/https://www.drugs.com/sfx/linezolid-side-effects.html|archive-date=20 December 2016}}</ref>

<!-- Mechanism of action -->
As a [[protein synthesis inhibitor]], linezolid works by suppressing [[bacterial translation|bacterial protein production]].<ref name=Swaney1998/> This either [[bacteriostatic|stops growth]] or results in [[bactericidal|bacterial death]].<ref name=AHFS2016/> Although many antibiotics work this way, the exact [[mechanism of action]] of linezolid appears to be unique in that it blocks the initiation of protein production, rather than one of the later steps.<ref name=Swaney1998>{{cite journal | vauthors = Swaney SM, Aoki H, Ganoza MC, Shinabarger DL | title = The oxazolidinone linezolid inhibits initiation of protein synthesis in bacteria | journal = Antimicrobial Agents and Chemotherapy | volume = 42 | issue = 12 | pages = 3251–5 | date = December 1998 | pmid = 9835522 | pmc = 106030 | url = | doi = 10.1128/AAC.42.12.3251 }}</ref> As of 2014, [[bacterial resistance]] to linezolid has remained low.<ref>{{cite journal | vauthors = Mendes RE, Deshpande LM, Jones RN | title = Linezolid update: stable in vitro activity following more than a decade of clinical use and summary of associated resistance mechanisms | journal = Drug Resistance Updates | volume = 17 | issue = 1–2 | pages = 1–12 | date = April 2014 | pmid = 24880801 | doi = 10.1016/j.drup.2014.04.002 | quote = Emergence of resistance has been limited&nbsp;... It is still uncertain whether the occurrences of such isolates are becoming more prevalent. }}</ref> Linezolid is a member of the [[2-Oxazolidone|oxazolidinone]] class of medications.<ref name=AHFS2016/>

<!-- History and culture -->
Linezolid was discovered in the mid-1990s, and was approved for commercial use in 2000.<ref>{{cite book| vauthors = Li JJ, Corey EJ  |title=Drug Discovery: Practices, Processes, and Perspectives|date=2013|publisher=John Wiley & Sons|isbn=978-1-118-35446-9|page=6|url=https://books.google.com/books?id=mIyxO5cLEAcC&pg=PA6|language=en|url-status=live|archive-url=https://web.archive.org/web/20170910172617/https://books.google.com/books?id=mIyxO5cLEAcC&pg=PA6|archive-date=10 September 2017}}</ref><ref>{{cite book| vauthors = Torok E, Moran E, Cooke F |title=Oxford Handbook of Infectious Diseases and Microbiology|date=2009|publisher=OUP Oxford|isbn=978-0-19-103962-1|chapter-url=https://books.google.com/books?id=5W-WBQAAQBAJ&pg=PT56|language=en|chapter=Chapter 2 Antimicrobials|url-status=live|archive-url=https://web.archive.org/web/20170908143257/https://books.google.com/books?id=5W-WBQAAQBAJ&pg=PT56|archive-date=8 September 2017}}</ref> It is on the [[WHO Model List of Essential Medicines|World Health Organization's List of Essential Medicines]].<ref name="WHO23rd">{{cite book | vauthors = ((World Health Organization)) | title = The selection and use of essential medicines 2023: web annex A: World Health Organization model list of essential medicines: 23rd list (2023) | year = 2023 | hdl = 10665/371090 | author-link = World Health Organization | publisher = World Health Organization | location = Geneva | id = WHO/MHP/HPS/EML/2023.02 | hdl-access=free }}</ref> The World Health Organization classifies linezolid as critically important for human medicine.<ref>{{cite book | vauthors=((World Health Organization)) | year=2019 | title=Critically important antimicrobials for human medicine | edition=6th revision |  author-link = World Health Organization | publisher = World Health Organization | location = Geneva | hdl=10665/312266 | isbn=9789241515528 | hdl-access=free }}</ref> Linezolid is available as a [[generic medication]].<ref name=AHFS2016>{{cite web|title=Linezolid|url=https://www.drugs.com/monograph/linezolid.html|publisher=The American Society of Health-System Pharmacists|access-date=8 December 2016|url-status=live|archive-url=https://web.archive.org/web/20161220231329/https://www.drugs.com/monograph/linezolid.html|archive-date=20 December 2016}}</ref> 
{{TOC limit}}

==Medical uses==
The main use of linezolid is the treatment of severe infections caused by [[Aerobic organism|aerobic]] [[Gram-positive bacteria]] that are [[antibiotic resistance|resistant]] to other antibiotics; it should not be used against bacteria that are sensitive to drugs with a narrower spectrum of activity, such as [[penicillin]]s and [[cephalosporin]]s. In both the popular press and the scientific literature, linezolid has been called a "reserve antibiotic"—one that should be used sparingly so that it will remain effective as a [[drug of last resort]] against potentially intractable infections.<ref>{{cite news | vauthors = Wroe D |title=An antibiotic to fight immune bugs |work=[[The Age]] |date=28 February 2002 |access-date=16 May 2009 |url=http://www.theage.com.au/articles/2002/02/27/1014704966995.html |url-status=live |archive-url=https://web.archive.org/web/20100127140624/http://www.theage.com.au/articles/2002/02/27/1014704966995.html |archive-date=27 January 2010 }}</ref><ref name=Wilson>{{cite journal | vauthors = Wilson AP, Cepeda JA, Hayman S, Whitehouse T, Singer M, Bellingan G | title = In vitro susceptibility of Gram-positive pathogens to linezolid and teicoplanin and effect on outcome in critically ill patients | journal = The Journal of Antimicrobial Chemotherapy | volume = 58 | issue = 2 | pages = 470–3 | date = August 2006 | pmid = 16735420 | doi = 10.1093/jac/dkl233 | doi-access = free }}</ref><ref name="Bozdogan">{{cite journal | vauthors = Bozdogan B, Appelbaum PC | title = Oxazolidinones: activity, mode of action, and mechanism of resistance | journal = International Journal of Antimicrobial Agents | volume = 23 | issue = 2 | pages = 113–9 | date = February 2004 | pmid = 15013035 | doi = 10.1016/j.ijantimicag.2003.11.003 }}</ref>

In the United States, the indications for linezolid use approved by the U.S. [[Food and Drug Administration]] (FDA) are the treatment of [[vancomycin-resistant Enterococcus|vancomycin-resistant ''Enterococcus'']] [[Enterococcus faecium|''faecium'']] [[infections]], with or without [[bacteremia|bacterial invasion of the bloodstream]]; [[nosocomial pneumonia]] (hospital-acquired) and [[community-acquired pneumonia]] caused by ''S. aureus'' or ''S. pneumoniae''; [[complicated skin and skin structure infection]]s (cSSSI) caused by susceptible bacteria, including [[diabetic foot]] infection, unless complicated by [[osteomyelitis]] (infection of the bone and bone marrow); and ''uncomplicated'' skin and soft tissue infections caused by ''S. pyogenes'' or ''S. aureus''.<ref name="Zyvox FDA label" /> The manufacturer advises against the use of linezolid for community-acquired pneumonia or ''uncomplicated'' skin and soft tissue infections caused by MRSA.<ref name="Zyvox FDA label" /> In the United Kingdom, pneumonia and cSSSIs are the only indications noted in the product labeling.<ref name="Zyvox SPC">{{cite web |url=http://emc.medicines.org.uk/medicine/9857 |title=Zyvox 600 mg Film-Coated Tablets, 100 mg/5 ml Granules for Oral Suspension, 2 mg/ml Solution for Infusion&nbsp;– Summary of Product Characteristics (SPC) |publisher=electronic Medicines Compendium |date=24 June 2009 |access-date=3 July 2009 |archive-url=https://web.archive.org/web/20120806161920/http://www.medicines.org.uk/emc/medicine/9857 |archive-date=6 August 2012 |url-status=dead }}</ref>

Linezolid appears to be as safe and effective for use in children and newborns as it is in adults.<ref name=Herrmann/><!-- Linezolid is available in three forms: as tablets, powder for the preparation of an oral suspension, and a ready-to-use solution for intravenous injection.<ref name="Zyvox FDA label" /><ref name=InfectiousDiseases/> -->

===Skin and soft tissue infections===
A large [[meta-analysis]] of randomized controlled trials found linezolid to be more effective than glycopeptide antibiotics (such as vancomycin and [[teicoplanin]]) and [[beta-lactam antibiotic]]s in the treatment of skin and soft tissue infections (SSTIs) caused by Gram-positive bacteria,<ref name=Falagas2008>{{cite journal |vauthors=Falagas ME, Siempos II, Vardakas KZ |title=Linezolid versus glycopeptide or beta-lactam for treatment of Gram-positive bacterial infections: meta-analysis of randomised controlled trials |journal=Lancet Infectious Diseases |volume=8 |issue=1 |pages=53–66 |date=January 2008 |pmid=18156089 |doi=10.1016/S1473-3099(07)70312-2 |issn=1473-3099}} Structured abstract with quality assessment available at [http://www.crd.york.ac.uk/CRDWeb/ShowRecord.asp?ID=12008005415 DARE] {{webarchive|url=https://web.archive.org/web/20111004094022/http://www.crd.york.ac.uk/CRDWeb/ShowRecord.asp?ID=12008005415 |date=4 October 2011 }}.</ref> and smaller studies appear to confirm its superiority over teicoplanin in the treatment of all serious Gram-positive infections.<ref name=Tascini>{{cite journal  |vauthors=Tascini C, Gemignani G, Doria R, etal |title=Linezolid treatment for gram-positive infections: a retrospective comparison with teicoplanin |journal=Journal of Chemotherapy |volume=21 |issue=3 |pages=311–6 |date=June 2009 |pmid=19567352 |issn=1120-009X |doi=10.1179/joc.2009.21.3.311|s2cid=19381342 }}</ref>

In the treatment of diabetic foot infections, linezolid appears to be cheaper and more effective than vancomycin.<ref name=Chow>{{cite journal | vauthors = Chow I, Lemos EV, Einarson TR | title = Management and prevention of diabetic foot ulcers and infections: a health economic review | journal = PharmacoEconomics | volume = 26 | issue = 12 | pages = 1019–35 | year = 2008 | pmid = 19014203 | doi = 10.2165/0019053-200826120-00005 | s2cid = 30903985 }}</ref> In a 2004 [[open-label study]], it was as effective as [[ampicillin/sulbactam]] and [[amoxicillin/clavulanic acid]], and far superior in patients with foot ulcers and no [[osteomyelitis]], but with significantly higher rates of adverse effects.<ref name=Lipsky>{{cite journal | vauthors = Lipsky BA, Itani K, Norden C | title = Treating foot infections in diabetic patients: a randomized, multicenter, open-label trial of linezolid versus ampicillin-sulbactam/amoxicillin-clavulanate | journal = Clinical Infectious Diseases | volume = 38 | issue = 1 | pages = 17–24 | date = January 2004 | pmid = 14679443 | doi = 10.1086/380449 | s2cid = 20586344 | doi-access =  }}</ref><ref name=Pigrau>{{cite journal | vauthors = Pigrau C, Almirante B | title = [Oxazolidinones, glycopeptides and cyclic lipopeptides] | language = es | journal = Enfermedades Infecciosas y Microbiologia Clinica | volume = 27 | issue = 4 | pages = 236–46 | date = April 2009 | pmid = 19406516 | doi = 10.1016/j.eimc.2009.02.004 | url = http://www.elsevier.es/sites/default/files/elsevier/pdf/28/28v27n04a13136682pdf001.pdf | trans-title = Oxazolidinones, glycopeptides and cyclic lipopeptides | archive-url = https://web.archive.org/web/20110723082633/http://www.elsevier.es/sites/default/files/elsevier/pdf/28/28v27n04a13136682pdf001.pdf | url-status = dead | archive-date = 23 July 2011 }}</ref> A 2008 meta-analysis of 18 randomized controlled trials, however, found that linezolid treatment failed as often as other antibiotics, regardless of whether patients had osteomyelitis.<ref name=Vardakas>{{cite journal | vauthors = Vardakas KZ, Horianopoulou M, Falagas ME | title = Factors associated with treatment failure in patients with diabetic foot infections: An analysis of data from randomized controlled trials | journal = Diabetes Research and Clinical Practice | volume = 80 | issue = 3 | pages = 344–51 | date = June 2008 | pmid = 18291550 | doi = 10.1016/j.diabres.2008.01.009 }}</ref>

Some authors have recommended that combinations of cheaper or more cost-effective drugs (such as [[co-trimoxazole]] with [[rifampicin]] or [[clindamycin]]) be tried before linezolid in the treatment of SSTIs when susceptibility of the causative organism allows it.<ref name=Pigrau/><ref>{{cite journal |vauthors=Grammatikos A, Falagas ME |title=Linezolid for the treatment of skin and soft tissue infection |journal=[[Expert Review of Dermatology]] |volume=3 |issue=5 |pages=539–48 |year=2008 |doi=10.1586/17469872.3.5.539}}</ref>

===Pneumonia===
No significant difference appears in treatment success rates between linezolid, glycopeptides, or appropriate beta-lactam antibiotics in the treatment of pneumonia.<ref name=Falagas2008/> [[Medical guideline|Clinical guideline]]s for the treatment of community-acquired pneumonia developed by the [[American Thoracic Society]] and the [[Infectious Diseases Society of America]] recommend that linezolid be reserved for cases in which MRSA has been confirmed as the causative organism, or when MRSA infection is suspected based on the clinical presentation.<ref name=USCAPGuidelines>{{cite journal  |vauthors=Mandell LA, Wunderink RG, Anzueto A, etal |title=Infectious Diseases Society of America/American Thoracic Society consensus guidelines on the management of community-acquired pneumonia in adults |journal=Clinical Infectious Diseases |volume=44 |issue=Suppl 2 |pages=S27–72 |date=March 2007 |pmid=17278083 |doi=10.1086/511159 |pmc=7107997 |issn=1058-4838|doi-access=free }}</ref> The guidelines of the [[British Thoracic Society]] do not recommend it as first-line treatment, but rather as an alternative to vancomycin.<ref name=BTSCAPGuidelines>{{cite web|url=http://www.brit-thoracic.org.uk/Portals/0/Clinical%20Information/Pneumonia/Guidelines/MACAPrevisedApr04.pdf |title=BTS guidelines for the management of community acquired pneumonia in adults&nbsp;– 2004 update |author=BTS Pneumonia Guidelines Committee |publisher=[[British Thoracic Society]] |date=30 April 2004 |access-date=30 June 2009 |url-status=dead |archive-url=https://web.archive.org/web/20090407092653/http://www.brit-thoracic.org.uk/Portals/0/Clinical%20Information/Pneumonia/Guidelines/MACAPrevisedApr04.pdf |archive-date=7 April 2009 }}</ref> Linezolid is also an acceptable second-line treatment for community-acquired pneumococcal pneumonia when penicillin resistance is present.<ref name=USCAPGuidelines/>

U.S. guidelines recommend either linezolid or vancomycin as the first-line treatment for hospital-acquired (nosocomial) MRSA pneumonia.<ref name=USHAPGuideline>{{cite journal |author=American Thoracic Society |author-link=American Thoracic Society |author2 = Infectious Diseases Society |author-link2 = Infectious Diseases Society of America |title=Guidelines for the management of adults with hospital-acquired, ventilator-associated, and healthcare-associated pneumonia |journal=American Journal of Respiratory and Critical Care Medicine |volume=171 |issue=4 |pages=388–416 |date=February 2005 |pmid=15699079 |doi=10.1164/rccm.200405-644ST  |s2cid=14907563 }}</ref> Some studies have suggested that linezolid is better than vancomycin against nosocomial pneumonia, particularly [[ventilator-associated pneumonia]] caused by MRSA, perhaps because the penetration of linezolid into bronchial fluids is much higher than that of vancomycin. Several issues in study design have been raised, however, calling into question results that suggest the superiority of linezolid.<ref name=Pigrau/> Regardless, linezolid's advantages include its high [[oral bioavailability]]—which allows easy switching to oral therapy—and the fact that poor kidney function is not an obstacle to use.<ref name=USHAPGuideline/> In contrast, achieving the correct dosage of vancomycin in patients with [[kidney failure]] is very difficult.<ref name=USHAPGuideline/>

===Other===
[[File:Endocarditis ultrasound.JPG|thumb|This [[echocardiography|echocardiogram]] shows vegetations on the [[tricuspid valve]] (white arrow) caused by infective endocarditis. The patient received conventional treatment, with [[ampicillin]], [[imipenem]], and [[glucocorticoid]]s, and recovered fully after heart surgery.<ref>{{cite journal | vauthors = Koya D, Shibuya K, Kikkawa R, Haneda M | title = Successful recovery of infective endocarditis-induced rapidly progressive glomerulonephritis by steroid therapy combined with antibiotics: a case report | journal = BMC Nephrology | volume = 5 | issue = 1 | pages = 18 | date = December 2004 | pmid = 15610562 | pmc = 544880 | doi = 10.1186/1471-2369-5-18 | doi-access = free }}</ref>|alt=Side-by-side echocardiogram cross-sections of a human heart. In the second image a white arrow points at a mass on the tricuspid valve.]]

It is traditionally believed that so-called "deep" infections—such as osteomyelitis or [[infective endocarditis]]—should be treated with bactericidal antibiotics, not bacteriostatic ones. Nevertheless, preclinical studies were conducted to assess the efficacy of linezolid for these infections,<ref name=Barbachyn/> and the drug has been used successfully to treat them in clinical practice. Linezolid appears to be a reasonable therapeutic option for infective endocarditis caused by multi-resistant Gram-positive bacteria, despite a lack of high-quality evidence to support this use.<ref>{{cite journal |vauthors=Pankey GA, Sabath LD |title=Clinical relevance of bacteriostatic versus bactericidal mechanisms of action in the treatment of Gram-positive bacterial infections |journal=[[Clinical Infectious Diseases]] |volume=38 |issue=6 |pages=864–70 |date=March 2004 |pmid=14999632 |doi=10.1086/381972 |issn=1058-4838|doi-access=free }}</ref><ref name=Falagas>{{cite journal |vauthors=Falagas ME, Manta KG, Ntziora F, Vardakas KZ |title=Linezolid for the treatment of patients with endocarditis: a systematic review of the published evidence |journal=Journal of Antimicrobial Chemotherapy |volume=58 |issue=2 |pages=273–80 |date=August 2006 |pmid=16735427 |doi=10.1093/jac/dkl219 |doi-access=free }}</ref> Results in the treatment of enterococcal endocarditis have varied, with some cases treated successfully and others not responding to therapy.<ref>{{cite journal |vauthors=Babcock HM, Ritchie DJ, Christiansen E, Starlin R, Little R, Stanley S |title=Successful treatment of vancomycin-resistant ''Enterococcus'' endocarditis with oral linezolid |journal=Clinical Infectious Diseases |volume=32 |issue=9 |pages=1373–5 |date=May 2001 |pmid=11303275 |doi=10.1086/319986 |issn=1058-4838|doi-access=free }}</ref><ref>{{cite journal |vauthors=Ang JY, Lua JL, Turner DR, Asmar BI |title=Vancomycin-resistant ''Enterococcus faecium'' endocarditis in a premature infant successfully treated with linezolid |journal=The Pediatric Infectious Disease Journal |volume=22 |issue=12 |pages=1101–3 |date=December 2003 |pmid=14688576 |doi=10.1097/01.inf.0000101784.83146.0c |issn=0891-3668|doi-access=free }}</ref><ref>{{cite journal |vauthors=Archuleta S, Murphy B, Keller MJ |title=Successful treatment of vancomycin-resistant ''Enterococcus faecium'' endocarditis with linezolid in a renal transplant recipient with human immunodeficiency virus infection |journal=Transplant Infectious Disease |volume=6 |issue=3 |pages=117–9 |date=September 2004 |pmid=15569227 |doi=10.1111/j.1399-3062.2004.00059.x |s2cid=40817941 |issn=1398-2273}}</ref><ref>{{cite journal |vauthors=Zimmer SM, Caliendo AM, Thigpen MC, Somani J |title=Failure of linezolid treatment for enterococcal endocarditis |journal=Clinical Infectious Diseases |volume=37 |issue=3 |pages=e29–30 |date=August 2003 |pmid=12884185 |doi=10.1086/375877 |issn=1058-4838}}</ref><ref>{{cite journal |vauthors=Tsigrelis C, Singh KV, Coutinho TD, Murray BE, Baddour LM |title=Vancomycin-Resistant Enterococcus faecalis Endocarditis: Linezolid Failure and Strain Characterization of Virulence Factors |journal=[[Journal of Clinical Microbiology]] |volume=45 |issue=2 |pages=631–5 |date=February 2007 |pmid=17182759 |pmc=1829077 |doi=10.1128/JCM.02188-06 }}</ref><ref>{{cite journal |vauthors=Berdal JE, Eskesen A |title=Short-term success, but long-term treatment failure with linezolid for enterococcal endocarditis |journal=Scandinavian Journal of Infectious Diseases |volume=40 |issue=9 |pages=765–6 |year=2008 |pmid=18609208 |doi=10.1080/00365540802087209 |s2cid=12651659 |issn=0036-5548}}</ref> [[Evidence-based medicine#Assessing the quality of evidence|Low- to medium-quality evidence]] is also mounting for its use in bone and joint infections, including chronic osteomyelitis, although adverse effects are a significant concern when long-term use is necessary.<ref>{{cite journal |vauthors=Falagas ME, Siempos II, Papagelopoulos PJ, Vardakas KZ |title=Linezolid for the treatment of adults with bone and joint infections |journal=International Journal of Antimicrobial Agents |volume=29 |issue=3 |pages=233–9 |date=March 2007 |pmid=17204407 |doi=10.1016/j.ijantimicag.2006.08.030 |issn=0924-8579}} Review.</ref><ref>{{cite journal  |vauthors=Bassetti M, Vitale F, Melica G, etal |title=Linezolid in the treatment of Gram-positive prosthetic joint infections |journal=Journal of Antimicrobial Chemotherapy |volume=55 |issue=3 |pages=387–90 |date=March 2005 |pmid=15705640 |doi=10.1093/jac/dki016 |doi-access=free }}</ref><ref>{{cite journal |vauthors=Aneziokoro CO, Cannon JP, Pachucki CT, Lentino JR |title=The effectiveness and safety of oral linezolid for the primary and secondary treatment of osteomyelitis |journal=Journal of Chemotherapy |volume=17 |issue=6 |pages=643–50 |date=December 2005 |pmid=16433195 |issn=1120-009X |doi=10.1179/joc.2005.17.6.643|s2cid=46391229 }}</ref><ref>{{cite journal  |vauthors=Senneville E, Legout L, Valette M, etal |title=Effectiveness and tolerability of prolonged linezolid treatment for chronic osteomyelitis: a retrospective study |journal=Clinical Therapeutics |volume=28 |issue=8 |pages=1155–63 |date=August 2006 |pmid=16982292 |doi=10.1016/j.clinthera.2006.08.001 |issn=0149-2918}}</ref><ref>{{cite journal |vauthors=Rao N, Hamilton CW |title=Efficacy and safety of linezolid for Gram-positive orthopedic infections: a prospective case series |journal=Diagnostic Microbiology and Infectious Disease |volume=59 |issue=2 |pages=173–9 |date=October 2007 |pmid=17574788 |doi=10.1016/j.diagmicrobio.2007.04.006 |issn=0732-8893}}</ref><ref>{{cite journal |vauthors=Papadopoulos A, Plachouras D, Giannitsioti E, Poulakou G, Giamarellou H, Kanellakopoulou K |title=Efficacy and tolerability of linezolid in chronic osteomyelitis and prosthetic joint infections: a case-control study |journal=Journal of Chemotherapy |volume=21 |issue=2 |pages=165–9 |date=April 2009 |pmid=19423469 |issn=1120-009X |doi=10.1179/joc.2009.21.2.165|s2cid=12400080 }}</ref>

In combination with other drugs, linezolid has been used to [[Tuberculosis treatment|treat tuberculosis]].<ref name=Lippea2006>{{cite journal | vauthors = von der Lippe B, Sandven P, Brubakk O | title = Efficacy and safety of linezolid in multidrug resistant tuberculosis (MDR-TB)--a report of ten cases | journal = The Journal of Infection | volume = 52 | issue = 2 | pages = 92–6 | date = February 2006 | pmid = 15907341 | doi = 10.1016/j.jinf.2005.04.007 }}</ref> The optimal dose for this purpose has not been established.  In adults, daily and twice-daily dosing have been used to good effect. Many months of treatment are often required, and the rate of adverse effects is high regardless of dosage.<ref name="Park2006">{{cite journal | vauthors = Park IN, Hong SB, Oh YM, Kim MN, Lim CM, Lee SD, Koh Y, Kim WS, Kim DS, Kim WD, Shim TS | title = Efficacy and tolerability of daily-half dose linezolid in patients with intractable multidrug-resistant tuberculosis | journal = The Journal of Antimicrobial Chemotherapy | volume = 58 | issue = 3 | pages = 701–4 | date = September 2006 | pmid = 16857689 | doi = 10.1093/jac/dkl298 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Fortún J, Martín-Dávila P, Navas E, Pérez-Elías MJ, Cobo J, Tato M, De la Pedrosa EG, Gómez-Mampaso E, Moreno S | title = Linezolid for the treatment of multidrug-resistant tuberculosis | journal = The Journal of Antimicrobial Chemotherapy | volume = 56 | issue = 1 | pages = 180–5 | date = July 2005 | pmid = 15911549 | doi = 10.1093/jac/dki148 | doi-access = free }}</ref> There is not enough reliable evidence of efficacy and safety to support this indication as a routine use.<ref name=Herrmann/>

Linezolid has been studied as an alternative to vancomycin in the treatment of [[febrile neutropenia]] in cancer patients when Gram-positive infection is suspected.<ref>{{cite journal |vauthors=Jaksic B, Martinelli G, Perez-Oteyza J, Hartman CS, Leonard LB, Tack KJ |title=Efficacy and safety of linezolid compared with vancomycin in a randomized, double-blind study of febrile neutropenic patients with cancer |journal=Clinical Infectious Diseases |volume=42 |issue=5 |pages=597–607 |date=March 2006 |pmid=16447103 |doi=10.1086/500139 |issn=1058-4838|doi-access=free }} Criticism in {{doi|10.1086/504431}}; author reply in {{doi|10.1086/504437}}.</ref> It is also one of few antibiotics that diffuse into the [[vitreous humor]], and may therefore be effective in treating [[endophthalmitis]] (inflammation of the inner linings and cavities of the eye) caused by susceptible bacteria. Again, there is little evidence for its use in this setting, as infectious endophthalmitis is treated widely and effectively with vancomycin [[intravitreal administration|injected directly into the eye]].<ref name=Pigrau/>

====Infections of the central nervous system====
In animal studies of [[meningitis]] caused by ''Streptococcus pneumoniae'', linezolid was found to penetrate well into [[cerebrospinal fluid]], but its effectiveness was inferior to that of other antibiotics.<ref name=Moellering/><ref>{{cite journal |vauthors=Cottagnoud P, Gerber CM, Acosta F, Cottagnoud M, Neftel K, Täuber MG |title=Linezolid against penicillin-sensitive and -resistant pneumococci in the rabbit meningitis model |journal=Journal of Antimicrobial Chemotherapy |volume=46 |issue=6 |pages=981–5 |date=December 2000 |pmid=11102418 |doi=10.1093/jac/46.6.981|doi-access=free }}</ref> There does not appear to be enough high-quality evidence to support the routine use of linezolid to treat bacterial meningitis. Nonetheless, it has been used successfully in many cases of [[central nervous system]] infection—including meningitis—caused by susceptible bacteria, and has also been suggested as a reasonable choice for this indication when treatment options are limited or when other antibiotics have failed.<ref name=Sabbatani/><ref>{{cite journal |vauthors=Ntziora F, Falagas ME |title=Linezolid for the treatment of patients with central nervous system infection |journal=Annals of Pharmacotherapy |volume=41 |issue=2 |pages=296–308 |date=February 2007 |pmid=17284501 |doi=10.1345/aph.1H307 |s2cid=33514115 |issn=1060-0280}} Structured abstract with quality assessment available at [http://www.crd.york.ac.uk/CRDWeb/ShowRecord.asp?ID=12007005296 DARE] {{webarchive|url=https://web.archive.org/web/20110902114025/http://www.crd.york.ac.uk/CRDWeb/ShowRecord.asp?ID=12007005296 |date=2 September 2011 }}.</ref> The guidelines of the Infectious Diseases Society of America recommend linezolid as the first-line drug of choice for VRE meningitis, and as an alternative to vancomycin for MRSA meningitis.<ref>{{cite journal  |vauthors=Tunkel AR, Hartman BJ, Kaplan SL, etal |title=Practice guidelines for the management of bacterial meningitis |journal=Clinical Infectious Diseases |volume=39 |issue=9 |pages=1267–84 |date=November 2004 |pmid=15494903 |doi=10.1086/425368 |issn=1058-4838|doi-access=free }}</ref> Linezolid appears superior to vancomycin in treating community-acquired MRSA infections of the central nervous system, although very few cases of such infections have been published ({{as of|2009|lc=on}}).<ref name=Naesens>{{cite journal |vauthors=Naesens R, Ronsyn M, Druwé P, Denis O, Ieven M, Jeurissen A |title=Central nervous system invasion by community-acquired methicillin-resistant ''Staphylococcus aureus'': case report and review of the literature |journal=[[Journal of Medical Microbiology]] |volume= 58|issue= Pt 9|pages= 1247–51|date=June 2009 |pmid=19528145 |doi=10.1099/jmm.0.011130-0 |issn=0022-2615}}</ref>

====Catheter-related infections====
In March 2007, the FDA reported the results of a [[randomized controlled trial|randomized]], [[open-label trial|open-label]], phase III clinical trial comparing linezolid to vancomycin in the treatment of [[central venous catheter#Infection|catheter-related bloodstream infections]]. Patients treated with vancomycin could be switched to [[oxacillin]] or [[dicloxacillin]] if the bacteria that caused their infection was found to be susceptible, and patients in both groups (linezolid and vancomycin) could receive specific treatment against Gram-negative bacteria if necessary.<ref name=CRBSI>{{cite web |author=[No authors listed] |url=https://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/DrugSafetyInformationforHeathcareProfessionals/ucm085249.htm |title=Information for Healthcare Professionals: Linezolid (marketed as Zyvox) |date=16 March 2007 |publisher=[[Food and Drug Administration (United States)|U.S. Food and Drug Administration]] (FDA) |access-date=15 September 2010 |url-status=dead |archive-url=https://web.archive.org/web/20101019044734/https://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/DrugSafetyInformationforHeathcareProfessionals/ucm085249.htm |archive-date=19 October 2010 }}</ref> The study itself was published in January 2009.<ref name=Wilcox>{{cite journal  |vauthors=Wilcox MH, Tack KJ, Bouza E, etal |title=Complicated skin and skin-structure infections and catheter-related bloodstream infections: noninferiority of linezolid in a phase 3 study |journal=Clinical Infectious Diseases |volume=48 |issue=2 |pages=203–12 |date=January 2009 |pmid=19072714 |doi=10.1086/595686 |issn=1058-4838|doi-access=free }}</ref>

Linezolid was associated with [[statistical significance|significant]]ly greater mortality than the comparator antibiotics. When data from all participants were pooled, the study found that 21.5% of those given linezolid died, compared to 16% of those not receiving it. The difference was found to be due to the inferiority of linezolid in the treatment of Gram-negative infections alone or mixed Gram-negative/Gram-positive infections. In participants whose infection was due to Gram-positive bacteria alone, linezolid was as safe and effective as vancomycin.<ref name=CRBSI/><ref name=Wilcox/> In light of these results, the FDA issued an alert reminding healthcare professionals that linezolid is not approved for the treatment of catheter-related infections or infections caused by Gram-negative organisms, and that more appropriate therapy should be instituted whenever a Gram-negative infection is confirmed or suspected.<ref name=CRBSI/>

===Specific populations===
In adults and children over the age of 12, linezolid is usually given every 12 hours, whether orally or intravenously.<ref name=Moellering/><ref name="American Family Physician"/> In younger children and infants, it is given every eight hours.<ref name=Buck>{{cite journal | vauthors = Buck ML |title=Linezolid use for resistant Gram-positive infections in children |journal=Pediatric Pharmacotherapy |volume=9 |issue=6 |date=June 2003 |url=http://www.healthsystem.virginia.edu/alive/pediatrics/PharmNews/200306.pdf |access-date=8 June 2009 |url-status=dead |archive-url=https://web.archive.org/web/20110605115607/http://www.healthsystem.virginia.edu/alive/pediatrics/PharmNews/200306.pdf |archive-date=5 June 2011 }}</ref> No dosage adjustments are required in the elderly, in people with mild-to-moderate liver failure, or in those with impaired kidney function.<ref name=Lexi-Comp/> In people requiring [[hemodialysis]], care should be taken to give linezolid after a session, because dialysis removes 30–40% of a dose from the body; no dosage adjustments are needed in people undergoing [[hemofiltration|continuous hemofiltration]],<ref name=Lexi-Comp/> although more frequent administration may be warranted in some cases.<ref name=Herrmann/> According to one study, linezolid may need to be given more frequently than normal in people with [[burn]]s affecting more than 20% of [[total body surface area|body area]], due to increased nonrenal clearance of the drug.<ref>{{cite journal  |vauthors=Lovering AM, Le Floch R, Hovsepian L, etal |title=Pharmacokinetic evaluation of linezolid in patients with major thermal injuries |journal=Journal of Antimicrobial Chemotherapy |volume=63 |issue=3 |pages=553–9 |date=March 2009 |pmid=19153078 |doi=10.1093/jac/dkn541 |issn=0305-7453|doi-access=free }}</ref>

Linezolid is in U.S. [[pregnancy category]] C, meaning there have been no adequate studies of its safety when used by pregnant women, and although animal studies have shown mild toxicity to the fetus, the benefits of using the drug may outweigh its risks.<ref name="Zyvox FDA label" /> It also passes into [[breast milk]], although the clinical significance of this (if any) is unknown.<ref name=InfectiousDiseases/>

===Spectrum of activity===
{{multiple image
| align     = right
| direction = vertical
| footer    = [[Scanning electron microscopy|Scanning electron micrograph]]s of [[vancomycin-resistant enterococcus|vancomycin-resistant ''Enterococcus'']] (top) and [[methicillin-resistant Staphylococcus aureus|methicillin-resistant ''Staphylococcus aureus'']] (bottom; false colors)
| width     = 200
| image1    = Vancomycin-Resistant Enterococcus 01.jpg
| alt1      = Black and white micrograph: a band of sphere-shaped bacteria, clustered in pairs, extends across a gray field.
| image2    = CDC-10046-MRSA.jpg
| alt2      = Colorized micrograph: sphere-shaped bacteria clustered in grape-like bunches.
}}
Linezolid is effective against all clinically important Gram-positive [[bacteria]]—those whose [[cell wall]] contains a thick layer of [[peptidoglycan]] and no [[bacterial outer membrane|outer membrane]]—notably ''[[Enterococcus faecium]]'' and ''[[Enterococcus faecalis]]'' (including [[vancomycin-resistant enterococcus|vancomycin-resistant enterococci]]), ''Staphylococcus aureus'' (including methicillin-resistant ''Staphylococcus aureus'', MRSA), ''[[Streptococcus agalactiae]]'', ''[[Streptococcus pneumoniae]]'', ''[[Streptococcus pyogenes]]'', the [[Streptococcus#Viridans and others|''viridans'' group streptococci]], ''[[Listeria monocytogenes]]'', and ''[[Corynebacterium]]'' species (the latter being among the most susceptible to linezolid, with [[minimum inhibitory concentration]]s routinely below 0.5&nbsp;mg/L).<ref name="Zyvox FDA label" /><ref name=Moellering/><ref name=Jones>{{cite journal |vauthors=Jones RN, Stilwell MG, Hogan PA, Sheehan DJ |title=Activity of Linezolid against 3,251 Strains of Uncommonly Isolated Gram-Positive Organisms: Report from the SENTRY Antimicrobial Surveillance Program |journal=Antimicrobial Agents and Chemotherapy |volume=51 |issue=4 |pages=1491–3 |date=April 2007 |pmid=17210770 |pmc=1855453 |doi=10.1128/AAC.01496-06}}</ref> Linezolid is also highly active ''[[in vitro]]'' against several [[Mycobacterium|mycobacteria]].<ref name=Moellering/> It appears to be very effective against ''[[Nocardia]]'', but because of high cost and potentially serious adverse effects, authors have recommended that it be combined with other antibiotics or reserved for cases that have failed traditional treatment.<ref>{{cite journal |vauthors=Jodlowski TZ, Melnychuk I, Conry J |title=Linezolid for the treatment of ''Nocardia'' spp. infections |journal=[[Annals of Pharmacotherapy]] |volume=41 |issue=10 |pages=1694–9 |date=October 2007 |pmid=17785610 |doi=10.1345/aph.1K196 |s2cid=33975237 |issn=1060-0280}}</ref>

Linezolid is considered [[bacteriostatic agent|bacteriostatic]] against most organisms—that is, it stops their growth and reproduction without actually killing them—but has some [[bactericide|bactericidal]] (killing) activity against streptococci.<ref name="Zyvox FDA label" /><ref name=DrugTherPerspect/> Some authors have noted that, despite its bacteriostatic effect ''in vitro'', linezolid "behaves" as a bactericidal antibiotic ''in vivo'' because it inhibits the production of [[exotoxin|toxin]]s by staphylococci and streptococci.<ref name=Barbachyn/> It also has a [[antimicrobial pharmacodynamics|post-antibiotic effect]] lasting one to four hours for most bacteria, meaning that bacterial growth is temporarily suppressed even after the drug is discontinued.<ref name=Herrmann>{{cite journal |vauthors=Herrmann DJ, Peppard WJ, Ledeboer NA, Theesfeld ML, Weigelt JA, Buechel BJ |title=Linezolid for the treatment of drug-resistant infections |journal=Expert Review of Anti-infective Therapy |volume=6 |issue=6 |pages=825–48 |date=December 2008 |pmid=19053895 |doi=10.1586/14787210.6.6.825 |s2cid=8791647 |issn=1478-7210}}</ref>

====Gram-negative bacteria====
Linezolid has no clinically significant effect on most [[Gram-negative bacteria]]. ''[[Pseudomonas]]'' and the [[Enterobacteriaceae]], for instance, are not susceptible.<ref name=DrugTherPerspect/> ''In vitro'', it is active against ''[[Pasteurella multocida]]'',<ref name="Zyvox FDA label" /><ref>{{cite web|url=http://www.hpa.org.uk/webw/HPAweb&HPAwebStandard/HPAweb_C/1195733833519?p=1203409654995 |title=Animal Bites and ''Pasteurella multocida'': Information for Healthcare Staff |author=[No authors listed] |publisher=[[Health Protection Agency]] |date=5 August 2008 |url-status=dead |archive-url=https://web.archive.org/web/20100126195237/http://www.hpa.org.uk/webw/HPAweb%26HPAwebStandard/HPAweb_C/1195733833519?p=1203409654995 |archive-date=26 January 2010 }} Retrieved on 15 May 2009.</ref> ''[[Fusobacterium]]'', ''[[Moraxella catarrhalis]]'', ''[[Legionella]]'', ''[[Bordetella]]'', and ''[[Elizabethkingia meningoseptica]]'', and moderately active (having a minimum inhibitory concentration for 90% of strains of 8&nbsp;mg/L) against ''[[Haemophilus influenzae]]''.<ref name=InfectiousDiseases>{{cite book |vauthors=Davaro RE, Glew RH, Daly JS |veditors= Gorbach SL, Bartlett JG, Blacklow NR | editor-link1 = Sherwood Gorbach |chapter=Oxazolidinones, quinupristin-dalfopristin, and daptomycin |chapter-url=https://books.google.com/books?id=91altE1evAsC&pg=PP241 |title=Infectious diseases |publisher=Lippincott Williams & Wilkins |location=Hagerstown, MD |year=2004 |pages=241–3 |isbn=978-0-7817-3371-7 |access-date=20 June 2009}}</ref><ref name=DrugTherPerspect/> It has also been used to great effect as a second-line treatment for ''[[Capnocytophaga]]'' infections.<ref name=Sabbatani>{{cite journal|vauthors=Sabbatani S, Manfredi R, Frank G, Chiodo F |title=Linezolid in the treatment of severe central nervous system infections resistant to recommended antimicrobial compounds |journal=Le Infezioni in Medicina |volume=13 |issue=2 |pages=112–9 |date=June 2005 |pmid=16220032 |url=http://www.infezmed.it/VisualizzaUnArticolo.aspx?Anno=2005&numero=2&ArticoloDaVisualizzare=Vol_13_2_2005_8 |issn=1124-9390 |url-status=dead |archive-url=https://web.archive.org/web/20110722035501/http://www.infezmed.it/VisualizzaUnArticolo.aspx?Anno=2005&numero=2&ArticoloDaVisualizzare=Vol_13_2_2005_8 |archive-date=22 July 2011 }}</ref><ref>{{cite journal |vauthors=Geisler WM, Malhotra U, Stamm WE |title=Pneumonia and sepsis due to fluoroquinolone-resistant ''Capnocytophaga gingivalis'' after autologous stem cell transplantation |journal=Bone Marrow Transplantation |volume=28 |issue=12 |pages=1171–3 |date=December 2001 |pmid=11803363 |doi=10.1038/sj.bmt.1703288 |s2cid=34825943 |issn=0268-3369 |doi-access= }}</ref>

====Comparable antibiotics====
Linezolid's spectrum of activity against Gram-positive bacteria is similar to that of the [[glycopeptide antibiotic]] [[vancomycin]], which has long been the standard for treatment of MRSA infections, and the two drugs are often compared.<ref name=Marino2007/><ref name=Herrmann/> Other comparable antibiotics include glycopeptide antibiotics such as [[teicoplanin]] (trade name Targocid), [[dalbavancin]] (Dalvance), [[oritavancin]] (Orbactiv), and [[telavancin]] (Vibativ); [[quinupristin/dalfopristin]] (Synercid, a combination of two [[streptogramin]]s, not active against ''E. faecalis'');<ref name=Livermore/> [[daptomycin]] (Cubicin, a [[lipopeptide]]); and [[ceftobiprole]] (Zevtera, a 5th-generation [[cephalosporin]]). Linezolid is the only one that can be taken by mouth for the treatment of systemic infections.<ref name=Herrmann/>

==Adverse effects==
When used for short periods, linezolid is a relatively safe drug.<ref name=Marino2007/> Common [[Adverse drug reaction|side effects]] of linezolid use (those occurring in more than 1% of people taking linezolid) include diarrhea (reported by 3–11% of clinical trial participants), headache (1–11%), nausea (3–10%), vomiting (1–4%), rash (2%), constipation (2%), altered taste perception (1–2%), and discoloration of the tongue (0.2–1%).<ref name=Lexi-Comp/> It has also been known to cause [[thrombocytopenia]]. Fungal infections such as [[Oral candidiasis|thrush]] and [[candidal vulvovaginitis|vaginal candidiasis]] may also occur as linezolid suppresses normal bacterial flora and opens a niche for fungi (so-called [[antibiotic candidiasis]]).<ref name=Lexi-Comp/> Less common (and potentially more serious) adverse effects include allergic reactions, [[pancreatitis]], and [[elevated transaminases]], which may be a sign of liver damage.<ref name=Lexi-Comp/><ref name=French>{{cite journal | vauthors = French G | title = Safety and tolerability of linezolid | journal = The Journal of Antimicrobial Chemotherapy | volume = 51 | issue = Suppl 2 | pages = ii45–53 | date = May 2003 | pmid = 12730142 | doi = 10.1093/jac/dkg253 | doi-access = free }} Review. Includes extensive discussion of the hematological adverse effects of linezolid.</ref> Unlike some antibiotics, such as [[erythromycin]] and the [[quinolone antibiotic|quinolones]], linezolid has no effect on the [[QT interval]], a measure of [[electrocardiography|cardiac electrical conduction]].<ref name=French/><ref name=Metaxas>{{cite journal | vauthors = Metaxas EI, Falagas ME | title = Update on the safety of linezolid | journal = Expert Opinion on Drug Safety | volume = 8 | issue = 4 | pages = 485–91 | date = July 2009 | pmid = 19538105 | doi = 10.1517/14740330903049706 | s2cid = 5691388 }}</ref> Adverse effects in children are similar to those that occur in adults.<ref name=Metaxas/>

Like nearly all antibiotics, linezolid has been associated with [[Clostridioides difficile infection|''Clostridioides difficile''-associated diarrhea]] (CDAD) and [[pseudomembranous colitis]], although the latter is uncommon, occurring in about one in two thousand patients in clinical trials.<ref name=Lexi-Comp/><ref name=French/><ref name=Metaxas/><ref>{{cite journal | vauthors = Zabel LT, Worm S | title = Linezolid contributed to Clostridium difficile colitis with fatal outcome | journal = Infection | volume = 33 | issue = 3 | pages = 155–7 | date = June 2005 | pmid = 15940418 | doi = 10.1007/s15010-005-4112-6 | s2cid = 37705529 }}</ref> ''C. difficile'' appears to be susceptible to linezolid ''in vitro'', and linezolid was even considered as a possible treatment for CDAD.<ref>{{cite journal | vauthors = Peláez T, Alonso R, Pérez C, Alcalá L, Cuevas O, Bouza E | title = In vitro activity of linezolid against Clostridium difficile | journal = Antimicrobial Agents and Chemotherapy | volume = 46 | issue = 5 | pages = 1617–8 | date = May 2002 | pmid = 11959617 | pmc = 127182 | doi = 10.1128/AAC.46.5.1617-1618.2002 }}</ref>

===Long-term use===
[[Bone marrow suppression]], characterized particularly by [[thrombocytopenia]] (low platelet count), may occur during linezolid treatment; it appears to be the only adverse effect that occurs [[statistical significance|significantly]] more frequently with linezolid than with glycopeptides or beta-lactams.<ref name=Falagas2008/> It is uncommon in patients who receive the drug for 14 days or fewer, but occurs much more frequently in patients who receive longer courses or who have renal failure.<ref name=French/><ref>{{cite journal | vauthors = Lin YH, Wu VC, Tsai IJ, Ho YL, Hwang JJ, Tsau YK, Wu CY, Wu KD, Hsueh PR | title = High frequency of linezolid-associated thrombocytopenia among patients with renal insufficiency | journal = International Journal of Antimicrobial Agents | volume = 28 | issue = 4 | pages = 345–351 | date = October 2006 | pmid = 16935472 | doi = 10.1016/j.ijantimicag.2006.04.017 }}</ref> A 2004 [[case report]] suggested that [[pyridoxine]] (a form of [[vitamin B6|vitamin B<sub>6</sub>]]) could reverse the anemia and thrombocytopenia caused by linezolid,<ref>{{cite journal |vauthors=Spellberg B, Yoo T, Bayer AS |title=Reversal of linezolid-associated cytopenias, but not peripheral neuropathy, by administration of vitamin B6 |journal=Journal of Antimicrobial Chemotherapy |volume=54 |issue=4 |pages=832–5 |date=October 2004 |pmid=15317746 |doi=10.1093/jac/dkh405 |doi-access=free }}</ref> but a later, larger study found no protective effect.<ref>{{cite journal | title=No effect of pyridoxine on the incidence of myelosuppression during prolonged linezolid treatment  |vauthors=Plachouras D, Giannitsioti E, Athanassia S, etal | journal=Clinical Infectious Diseases |date=November 2006 | volume=43 | issue=9 | pages=e89–91 | doi=10.1086/508280 | pmid=17029128  | issn=1058-4838| doi-access=free }}</ref>

Long-term use of linezolid has also been associated with [[chemotherapy-induced peripheral neuropathy]], a progressive and enduring often irreversible tingling numbness, intense pain, and hypersensitivity to cold, beginning in the hands and feet and sometimes involving the arms and legs.<ref name=NCI>{{cite journal| vauthors = del Pino BM |date=23 February 2010 |journal=NCI Cancer Bulletin |volume=7 |issue=4 |page=6 |title=Chemotherapy-induced Peripheral Neuropathy |url=http://www.cancer.gov/aboutnci/ncicancerbulletin/archive/2010/022310/page6 |url-status=dead|archive-url=https://web.archive.org/web/20111211105234/http://www.cancer.gov/aboutnci/ncicancerbulletin/archive/2010/022310/page6 |archive-date=11 December 2011 }}</ref> Chemotherapy drugs associated with CIPN include [[thalidomide]], the [[epothilone]]s such as [[ixabepilone]], the [[vinca alkaloid|''vinca'' alkaloids]] [[vincristine]] and [[vinblastine]],<ref>{{cite book|chapter = Africa's gift to the world|pages = 46–51|chapter-url = https://books.google.com/books?id=aXGmCwAAQBAJ&pg=PA46|title = Botanical Miracles: Chemistry of Plants That Changed the World| vauthors = Cooper R, Deakin JJ |publisher = [[CRC Press]]|year = 2016|isbn = 9781498704304}}</ref><ref>{{cite journal | vauthors = Keglevich P, Hazai L, Kalaus G, Szántay C | title = Modifications on the basic skeletons of vinblastine and vincristine | journal = Molecules | volume = 17 | issue = 5 | pages = 5893–914 | date = May 2012 | pmid = 22609781 | pmc = 6268133 | doi = 10.3390/molecules17055893 | doi-access = free }}</ref><ref>{{cite book| vauthors = Raviña E |title = The evolution of drug discovery: From traditional medicines to modern drugs|year = 2011|publisher = [[John Wiley & Sons]]|isbn = 9783527326693|pages = 157–159|chapter = Vinca alkaloids|chapter-url = https://books.google.com/books?id=iDNy0XxGqT8C&pg=PA157}}</ref> the [[taxane]]s [[paclitaxel]] and [[docetaxel]], the [[proteasome inhibitor]]s such as [[bortezomib]], and the platinum-based drugs [[cisplatin]], [[oxaliplatin]] and [[carboplatin]].<ref name = NCI/><ref>{{cite journal|url=http://www.kup.at/kup/pdf/10376.pdf|vauthors=Grisold W, Oberndorfer S, Windebank AJ|journal=European Association of Neurooncology Magazine|title=Chemotherapy and polyneuropathies|year=2012|volume=12|issue=1|url-status=live|archive-url=https://web.archive.org/web/20141006125234/http://www.kup.at/kup/pdf/10376.pdf|archive-date=6 October 2014}}</ref><ref>{{cite web | url=http://www.ehealthme.com/ds/herceptin/peripheral%20sensory%20neuropathy | title=Review: could Herceptin cause Peripheral sensory neuropathy | access-date=4 May 2016 | url-status=live | archive-url=https://web.archive.org/web/20160317105901/http://www.ehealthme.com/ds/herceptin/peripheral%20sensory%20neuropathy | archive-date=17 March 2016 }}</ref> and [[optic neuropathy]], which is most common after several months of treatment and may also be irreversible.<ref name=Narita>{{cite journal | vauthors = Narita M, Tsuji BT, Yu VL | title = Linezolid-associated peripheral and optic neuropathy, lactic acidosis, and serotonin syndrome | journal = Pharmacotherapy | volume = 27 | issue = 8 | pages = 1189–97 | date = August 2007 | pmid = 17655517 | doi = 10.1592/phco.27.8.1189 | s2cid = 40772687 }}</ref><ref name=Bressler>{{cite journal | vauthors = Bressler AM, Zimmer SM, Gilmore JL, Somani J | title = Peripheral neuropathy associated with prolonged use of linezolid | journal = The Lancet. Infectious Diseases | volume = 4 | issue = 8 | pages = 528–31 | date = August 2004 | pmid = 15288827 | doi = 10.1016/S1473-3099(04)01109-0 }}</ref><ref name=Brown>{{cite journal | vauthors = Brown J, Aitken SL, van Manen RP | title = Potential for linezolid-related blindness: a review of spontaneous adverse event reports | journal = Pharmacotherapy | volume = 31 | issue = 6 | pages = 585–90 | date = June 2011 | pmid = 21923442 | doi = 10.1592/phco.31.6.585 | s2cid = 28881160 }}</ref><ref name="pmid17766431">{{cite journal | vauthors = Chao CC, Sun HY, Chang YC, Hsieh ST | title = Painful neuropathy with skin denervation after prolonged use of linezolid | journal = Journal of Neurology, Neurosurgery, and Psychiatry | volume = 79 | issue = 1 | pages = 97–9 | date = January 2008 | pmid = 17766431 | doi = 10.1136/jnnp.2007.127910 | s2cid = 33138699 | pmc = 3029234 }}</ref><ref>{{cite journal | vauthors = Saijo T, Hayashi K, Yamada H, Wakakura M | title = Linezolid-induced optic neuropathy | journal = American Journal of Ophthalmology | volume = 139 | issue = 6 | pages = 1114–6 | date = June 2005 | pmid = 15953450 | doi = 10.1016/j.ajo.2004.11.047 }}</ref> Although the mechanism of injury is still poorly understood, [[mitochondrial toxicity]] has been proposed as a cause;<ref name=Barnhill/><ref name="Javaheri">{{cite journal | vauthors = Javaheri M, Khurana RN, O'hearn TM, Lai MM, Sadun AA | title = Linezolid-induced optic neuropathy: a mitochondrial disorder? | journal = The British Journal of Ophthalmology | volume = 91 | issue = 1 | pages = 111–5 | date = January 2007 | pmid = 17179125 | pmc = 1857552 | doi = 10.1136/bjo.2006.102541 }}</ref> linezolid is toxic to [[mitochondria]], probably because of the similarity between mitochondrial and bacterial [[ribosome]]s.<ref name=McKee>{{cite journal | vauthors = McKee EE, Ferguson M, Bentley AT, Marks TA | title = Inhibition of mammalian mitochondrial protein synthesis by oxazolidinones | journal = Antimicrobial Agents and Chemotherapy | volume = 50 | issue = 6 | pages = 2042–9 | date = June 2006 | pmid = 16723564 | pmc = 1479116 | doi = 10.1128/AAC.01411-05 }}</ref> [[Lactic acidosis]], a potentially life-threatening buildup of [[lactic acid]] in the body, may also occur due to mitochondrial toxicity.<ref name=Barnhill>{{cite journal | vauthors = Barnhill AE, Brewer MT, Carlson SA | title = Adverse effects of antimicrobials via predictable or idiosyncratic inhibition of host mitochondrial components | journal = Antimicrobial Agents and Chemotherapy | volume = 56 | issue = 8 | pages = 4046–51 | date = August 2012 | pmid = 22615289 | pmc = 3421593 | doi = 10.1128/AAC.00678-12 }} Review. For the original case series, see {{cite journal | vauthors = Soriano A, Miró O, Mensa J | title = Mitochondrial toxicity associated with linezolid | journal = The New England Journal of Medicine | volume = 353 | issue = 21 | pages = 2305–6 | date = November 2005 | pmid = 16306535 | doi = 10.1056/NEJM200511243532123 | doi-access = free }}</ref> Because of these long-term effects, the manufacturer recommends weekly [[complete blood count]]s during linezolid therapy to monitor for possible bone marrow suppression, and recommends that treatment last no more than 28 days.<ref name="Zyvox FDA label" /><ref name=French/> A more extensive monitoring protocol for early detection of toxicity in seriously ill patients receiving linezolid has been developed and proposed by a team of researchers in Melbourne, Australia. The protocol includes twice-weekly blood tests and [[liver function tests]]; measurement of serum [[lactic acid|lactate]] levels, for early detection of lactic acidosis; a review of all medications taken by the patient, interrupting the use of those that may [[drug interaction|interact]] with linezolid; and periodic eye and neurological exams in patients set to receive linezolid for longer than four weeks.<ref>{{cite journal | vauthors = Bishop E, Melvani S, Howden BP, Charles PG, Grayson ML | title = Good clinical outcomes but high rates of adverse reactions during linezolid therapy for serious infections: a proposed protocol for monitoring therapy in complex patients | journal = Antimicrobial Agents and Chemotherapy | volume = 50 | issue = 4 | pages = 1599–602 | date = April 2006 | pmid = 16569895 | pmc = 1426936 | doi = 10.1128/AAC.50.4.1599-1602.2006 }}</ref>

The adverse effects of long-term linezolid therapy were first identified during postmarketing surveillance. Bone marrow suppression was not identified during Phase III trials, in which treatment did not exceed 21 days. Although some participants of early trials did experience thrombocytopenia, it was found to be reversible and did not occur significantly more frequently than in controls (participants not taking linezolid).<ref name=Moellering/> There have also been postmarketing reports of [[seizure]]s, and, {{as of|2009|lc=on}}, a single case each of [[Bell's palsy]] (paralysis of the [[facial nerve]]) and [[nephrotoxicity|kidney toxicity]].<ref name=Metaxas/> Evidence of protein synthesis inhibition in mammalian cells by linezolid has been published.<ref>{{cite journal | vauthors = King MP, Attardi G | title = Human cells lacking mtDNA: repopulation with exogenous mitochondria by complementation | journal = Science | volume = 246 | issue = 4929 | pages = 500–3 | date = October 1989 | pmid = 2814477 | doi = 10.1126/science.2814477 | bibcode = 1989Sci...246..500K }}</ref>

==Interactions==
Linezolid is a weak, non-selective, reversible [[monoamine oxidase inhibitor]] (MAOI), and should not be used concomitantly with other MAOIs, large amounts of [[tyramine]]-rich foods (such as pork, aged cheeses, alcoholic beverages, or smoked and pickled foods), or [[Serotonin|serotonergic]] drugs. There have been [[postmarketing surveillance|postmarketing reports]] of [[serotonin syndrome]] when linezolid was given with or soon after the discontinuation of serotonergic drugs, particularly [[selective serotonin reuptake inhibitor]]s (SSRIs) such as [[paroxetine]] and [[sertraline]].<ref name=French/><ref>{{cite journal | vauthors = Lawrence KR, Adra M, Gillman PK | title = Serotonin toxicity associated with the use of linezolid: a review of postmarketing data | journal = Clinical Infectious Diseases | volume = 42 | issue = 11 | pages = 1578–83 | date = June 2006 | pmid = 16652315 | doi = 10.1086/503839 | doi-access = free }}</ref><ref name=Huang>{{cite journal | vauthors = Huang V, Gortney JS | title = Risk of serotonin syndrome with concomitant administration of linezolid and serotonin agonists | journal = Pharmacotherapy | volume = 26 | issue = 12 | pages = 1784–93 | date = December 2006 | pmid = 17125439 | doi = 10.1592/phco.26.12.1784 | s2cid = 24150415 }}</ref><ref>{{cite web |url=http://www.medscape.com/viewarticle/580101 |title=FDA Safety Changes: Mirena, Zyvox, Orencia | vauthors = Waknine Y |date=5 September 2008 |publisher=[[Medscape]] |access-date=6 September 2008 |url-status=live |archive-url=https://web.archive.org/web/20081202190427/http://www.medscape.com/viewarticle/580101 |archive-date=2 December 2008 }} Freely available with registration.</ref> It may also enhance the blood pressure-increasing effects of [[sympathomimetic drug]]s such as [[pseudoephedrine]] or [[phenylpropanolamine]].<ref name=Moellering/><ref name=Stalker>{{cite journal | vauthors = Stalker DJ, Jungbluth GL | title = Clinical pharmacokinetics of linezolid, a novel oxazolidinone antibacterial | journal = Clinical Pharmacokinetics | volume = 42 | issue = 13 | pages = 1129–40 | year = 2003 | pmid = 14531724 | doi = 10.2165/00003088-200342130-00004 | s2cid = 37436341 }}</ref> It should also not be given in combination with [[pethidine]] ([[meperidine]]) under any circumstance due to the risk of [[serotonin syndrome]].

Linezolid does not [[enzyme inhibitor|inhibit]] or [[regulation of gene expression|induce]] the [[cytochrome P450]] (CYP) system, which is responsible for the metabolism of many commonly used drugs, and therefore does not have any CYP-related interactions.<ref name="Zyvox FDA label" />

==Pharmacology==

===Pharmacodynamics===
{{further|Bacterial translation|Translation (genetics)#Basic mechanisms}}
[[File:Ribosome mRNA translation en.svg|thumb|Simplified schematic of mRNA translation. Linezolid occupies the A site (at center) and prevents tRNA from binding.|alt=Diagram: A colored ribbon, representing messenger RNA (mRNA), passes through a cartoon diagram of an assembled ribosome. Cartoon representations of transfer RNA (tRNA) enter and exit the ribosome and occupy its A and P sites. A string of colored spheres, representing a newly formed protein, comes out of the top of the ribosome.]]

Linezolid, like other [[oxazolidinones]], is a bacterial [[protein synthesis inhibitor]] and a weak, [[non-selective]], [[reversible inhibitor|reversible]] [[monoamine oxidase inhibitor]].<ref name=Roger2018 /><ref name="Oxazolidinones MAOI 2010 review">{{cite journal | vauthors = Renslo AR | title = Antibacterial oxazolidinones: emerging structure-toxicity relationships | journal = Expert Review of Anti-infective Therapy | volume = 8 | issue = 5 | pages = 565–74 | date = May 2010 | pmid = 20455685 | doi = 10.1586/eri.10.26 | s2cid = 23670767 }}</ref> As a protein synthesis inhibitor, linezolid stops the growth and reproduction of bacteria by disrupting [[Bacterial translation|translation]] of [[messenger RNA]] (mRNA) into [[protein]]s in bacterial [[ribosome]]s.<ref name=Roger2018 /> Linezolid inhibits translation at the first step of protein synthesis, ''[[MRNA-ribosome|initiation]]'',<ref name=Roger2018 /><ref name="Tedizolid and oxazolidinones 2015 review" /> unlike most other protein synthesis inhibitors, which inhibit ''[[Bacterial translation#Elongation|elongation]]''.<ref name=Swaney1998/><ref name="American Family Physician"/> It does so by preventing the formation of the initiation complex, composed of the [[30S]] and [[50S]] subunits of the ribosome, [[transfer RNA|tRNA]], and mRNA. Linezolid binds to the [[23S ribosomal RNA|23S]] portion of the 50S subunit (the center of [[peptidyl transferase]] activity),<ref name=Roger2018 /><ref name="Tedizolid and oxazolidinones 2015 review">{{cite journal | vauthors = Zhanel GG, Love R, Adam H, Golden A, Zelenitsky S, Schweizer F, Gorityala B, Lagacé-Wiens PR, Rubinstein E, Walkty A, Gin AS, Gilmour M, Hoban DJ, Lynch JP, Karlowsky JA | title = Tedizolid: a novel oxazolidinone with potent activity against multidrug-resistant gram-positive pathogens | journal = Drugs | volume = 75 | issue = 3 | pages = 253–70 | date = February 2015 | pmid = 25673021 | doi = 10.1007/s40265-015-0352-7 | s2cid = 3334681 }}</ref> close to the [[binding site]]s of [[chloramphenicol]], [[lincomycin]], and other antibiotics. Due to this unique mechanism of action, [[cross-resistance]] between linezolid and other protein synthesis inhibitors is highly infrequent or nonexistent.<ref name=Herrmann/><ref name=Moellering/>

In 2008, the [[crystal structure]] of linezolid bound to the 50S subunit of a ribosome from the [[archaea]]n ''Haloarcula marismortui'' was elucidated by a team of scientists from [[Yale University]] and deposited in the [[Protein Data Bank]].<ref>{{cite journal | vauthors = Ippolito JA, Kanyo ZF, Wang D, Franceschi FJ, Moore PB, Steitz TA, Duffy EM | title = Crystal structure of the oxazolidinone antibiotic linezolid bound to the 50S ribosomal subunit | journal = Journal of Medicinal Chemistry | volume = 51 | issue = 12 | pages = 3353–6 | date = June 2008 | pmid = 18494460 | doi = 10.1021/jm800379d }}</ref> Another team in 2008 determined the structure of linezolid bound to a 50S subunit of ''[[Deinococcus radiodurans]]''. The authors proposed a refined model for the mechanism of action of oxazolidinones, finding that linezolid occupies the [[MRNA-ribosome|A site]] of the 50S ribosomal subunit, inducing a [[conformational change]] that prevents tRNA from entering the site and ultimately forcing tRNA to separate from the ribosome.<ref>{{cite journal | vauthors = Wilson DN, Schluenzen F, Harms JM, Starosta AL, Connell SR, Fucini P | title = The oxazolidinone antibiotics perturb the ribosomal peptidyl-transferase center and effect tRNA positioning | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 105 | issue = 36 | pages = 13339–44 | date = September 2008 | pmid = 18757750 | pmc = 2533191 | doi = 10.1073/pnas.0804276105 | bibcode = 2008PNAS..10513339W | doi-access = free }}</ref>

===Pharmacokinetics===
[[File:Linezolid metabolism.svg|class=skin-invert-image|thumb|Major metabolites of linezolid|alt=Upper left: structural formula of the unaltered linezolid molecule, with the morpholino group highlighted in red. Lower left: main carboxylic acid metabolite, accounting for 10% of an excreted dose; the morpholine ring has been cleaved at the nitrogen atom. Lower right: structural formulae of two distinct molecules, a carboxylic acid and a lactone, with an equilibrium arrow between them; this metabolite accounts for 45% of a dose. Upper right: structure of a minor carboxylic acid metabolite, which accounts for aroune 3.3% of a dose.]]

One of the advantages of linezolid is that it has an [[absolute bioavailability|absolute oral bioavailability]] of 100% due to its rapid and complete [[absorption (pharmacology)|absorption]] after [[oral administration]];<ref name=Roger2018 /> in other words, the entire dose reaches the bloodstream, as if it had been given [[intravenous therapy|intravenously]].<ref name=Roger2018 /> This means that people receiving intravenous linezolid may be switched to oral linezolid as soon as their condition allows it, whereas comparable antibiotics (such as vancomycin and quinupristin/dalfopristin) can only be given intravenously.<ref name=Roger2018 /><ref name="American Family Physician">{{cite journal |vauthors=Ament PW, Jamshed N, Horne JP |title=Linezolid: its role in the treatment of gram-positive, drug-resistant bacterial infections |journal=[[American Family Physician]] |volume=65 |issue=4 |pages=663–70 |date=February 2002 |pmid=11871684 |url=http://www.aafp.org/afp/20020215/663.html |issn=0002-838X |url-status=live |archive-url=https://web.archive.org/web/20080724045942/http://www.aafp.org/afp/20020215/663.html |archive-date=24 July 2008 }}</ref>
Taking linezolid with food somewhat slows its absorption, but the [[area under the curve (pharmacokinetics)|area under the curve]] is not affected.<ref name=Herrmann/>

Linezolid's [[plasma protein binding]] is approximately 31% (range {{nowrap|4–32%}}) and its [[volume of distribution]] at [[steady state]] averages {{nowrap|36.1–47.3}}&nbsp;liters in healthy adult volunteers.<ref name=Roger2018 /> [[Peak plasma concentration]]s (C<sub>max</sub>) are reached one to two hours after administration of the drug.<!-- and are around 13&nbsp;mg/L after a single dose and 16–19&nbsp;mg/L after repeated administration;<ref name=Lexi-Comp/><ref name=Herrmann/> trough concentrations (C<sub>min</sub>) are 4–8&nbsp;mg/L.<ref name=Herrmann/> *see [[Wikipedia:Featured article candidates/Linezolid/archive1]] for an explanation of why this is commented out* --> Linezolid is readily distributed to all tissues in the body apart from [[bone]] matrix and [[white adipose tissue]].<ref name=Barbachyn/> Notably, the concentration of linezolid in the epithelial lining fluid (ELF) of the [[lower respiratory tract]] is at least equal to, and often higher than, that achieved in serum (some authors have reported [[bronchus|bronchial]] fluid concentrations up to four times higher than serum concentrations), which may account for its [[efficacy]] in treating pneumonia. However, a meta-analysis of clinical trials found that linezolid was not superior to [[vancomycin]], which achieves lower concentrations in the ELF.<ref name="Kalil et al">{{cite journal | vauthors = Kalil AC, Murthy MH, Hermsen ED, Neto FK, Sun J, Rupp ME | title = Linezolid versus vancomycin or teicoplanin for nosocomial pneumonia: a systematic review and meta-analysis | journal = Critical Care Medicine | volume = 38 | issue = 9 | pages = 1802–8 | date = September 2010 | pmid = 20639754 | doi = 10.1097/CCM.0b013e3181eb3b96 | s2cid = 6289226 }}</ref> [[Cerebrospinal fluid]] (CSF) concentrations vary; peak CSF concentrations are lower than serum ones, due to slow diffusion across the [[blood–brain barrier]], and trough concentrations in the CSF are higher for the same reason.<ref name=Herrmann/> The average half-life is three hours in children, four hours in teenagers, and five hours in adults.<ref name="Zyvox FDA label" />

Linezolid is [[drug metabolism|metabolized]] in the [[liver]], by [[redox|oxidation]] of the [[morpholine]] ring, without involvement of the [[cytochrome P450]] system. This metabolic pathway leads to two major inactive [[metabolite]]s (which each account for around 45% and 10% of an excreted dose at steady state), one minor metabolite, and several trace metabolites, none of which accounts for more than 1% of an excreted dose.<ref name=Slatter>{{cite journal | vauthors = Slatter JG, Stalker DJ, Feenstra KL, Welshman IR, Bruss JB, Sams JP, Johnson MG, Sanders PE, Hauer MJ, Fagerness PE, Stryd RP, Peng GW, Shobe EM | title = Pharmacokinetics, metabolism, and excretion of linezolid following an oral dose of [(14)C]linezolid to healthy human subjects | journal = Drug Metabolism and Disposition | volume = 29 | issue = 8 | pages = 1136–45 | date = August 2001 | pmid = 11454733 | url = http://dmd.aspetjournals.org/content/29/8/1136.full.pdf | access-date = 3 April 2011 | archive-date = 28 August 2021 | archive-url = https://web.archive.org/web/20210828144324/https://dmd.aspetjournals.org/content/29/8/1136 | url-status = live }}</ref> [[Clearance (medicine)|Clearance]] of linezolid varies with age and gender; it is fastest in children (which accounts for the shorter half-life), and appears to be 20% lower in women than in men.<ref name="Zyvox FDA label" /><ref name=Slatter/><ref name=Sisson>{{cite journal | vauthors = Sisson TL, Jungbluth GL, Hopkins NK | title = Age and sex effects on the pharmacokinetics of linezolid | journal = European Journal of Clinical Pharmacology | volume = 57 | issue = 11 | pages = 793–7 | date = January 2002 | pmid = 11868801 | doi = 10.1007/s00228-001-0380-y | s2cid = 38863420 }}</ref> There is a strong correlation between linezolid clearance and creatinine clearance.<ref name=Bialvaei>{{cite journal | vauthors = Zahedi Bialvaei A, Rahbar M, Yousefi M, Asgharzadeh M, Samadi Kafil H | title = Linezolid: a promising option in the treatment of Gram-positives | journal = The Journal of Antimicrobial Chemotherapy | volume = 72 | issue = 2 | pages = 354–364 | date = February 2017 | pmid = 27999068 | doi = 10.1093/jac/dkw450 | doi-access = free }}</ref>

==Chemistry==
At [[pH#Living systems|physiological pH]] (7.4), linezolid exists in an uncharged state. It is moderately water-soluble (approximately 3&nbsp;mg/mL), with a [[partition coefficient|log''P'']] of 0.55.<ref name=Herrmann/>

[[File:Linezolid showing oxazolidinone pharmacophore.svg|class=skin-invert-image|thumb|right|Numbered structure of linezolid, showing the [[pharmacophore]] required for good activity (in blue) and desirable structural features (in orange)|alt=Skeletal formula of N-<nowiki/>{[(5S)-3-[3-fluoro-4-(morpholin-4-yl)phenyl]-2-oxo-1,3-oxazolidin-5-yl]methyl}acetamide, highlighting the morpholino and fluoro groups in orange, with the rest in blue. The carbon atoms of the parent chain are numbered.]]

The oxazolidinone [[pharmacophore]]—the chemical "template" essential for antimicrobial [[biological activity|activity]]—consists of a [[2-Oxazolidone|1,3-oxazolidin-2-one]] [[functional group|moiety]] with an [[aryl]] group at position 3 and an ''S''-[[methyl group]], with another [[substituent]] attached to it, at position 5 (the ''R''-[[enantiomer]]s of all oxazolidinones are devoid of antibiotic properties).<ref name=Brickner/> In addition to this essential core, linezolid also contains several structural characteristics that improve its effectiveness and safety. An [[acetamide]] substituent on the 5-methyl group is the best choice in terms of antibacterial efficacy, and is used in all of the more active oxazolidinones developed thus far; in fact, straying too far from an acetamide group at this position makes the drug lose its antimicrobial power, although weak to moderate activity is maintained when some [[bioisostere|isosteric]] groups are used. A [[fluorine]] atom at the 3′ position practically doubles ''in vitro'' and ''in vivo'' activity, and the [[electron donor|electron-donating]] [[nitrogen]] atom in the [[morpholine]] ring helps maintain high antibiotic potency and an acceptable safety profile.<ref name=Barbachyn/><ref name=Brickner/>

The [[anticoagulant]] [[rivaroxaban]] (Xarelto) bears a striking structural similarity to linezolid; both drugs share the oxazolidinone pharmacophore, differing in only three areas (an extra [[ketone]] and chloro[[thiophene]], and missing the fluorine atom). However this similarity appears to carry no clinical significance.<ref>{{cite web |url=http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Assessment_Report_-_Variation/human/000944/WC500120736.pdf |title=CHP Assessment Report for Xarelto (EMA/CHMP/301607/2011) |author=European Medicines Agency |year=2011 |access-date=15 March 2012 |url-status=live |archive-url=https://web.archive.org/web/20120130062132/http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Assessment_Report_-_Variation/human/000944/WC500120736.pdf |archive-date=30 January 2012 }}</ref>

===Synthesis===
Linezolid is a completely [[organic synthesis|synthetic]] drug: it does not occur in nature (unlike erythromycin and many other antibiotics) and was not developed by building upon a naturally occurring skeleton (unlike most [[beta-lactam antibiotic|beta-lactam]]s, which are [[semisynthesis|semisynthetic]]). Many approaches are available for oxazolidinone synthesis, and several routes for the synthesis of linezolid have been reported in the chemistry literature.<ref name=Brickner/><ref name=Xu>{{cite journal|vauthors=Xu GY, Zhou Y, Xu MC |title=A convenient synthesis of antibacterial linezolid from (''S'')-glyceraldehyde acetonide |journal=Chinese Chemical Letters |volume=17 |issue=3 |pages=302–4 |year=2006 |url=http://www.imm.ac.cn/journal/ccl/1703/170306-302-b050449-p3.pdf |url-status=dead |archive-url=https://web.archive.org/web/20110707013015/http://www.imm.ac.cn/journal/ccl/1703/170306-302-b050449-p3.pdf |archive-date=7 July 2011 }}</ref> Despite good [[yield (chemistry)|yields]], the original method (developed by Upjohn for [[pilot plant]]-scale production of linezolid and eperezolid) is lengthy, requires the use of expensive chemicals—such as [[palladium on carbon]] and the highly sensitive reagents [[methanesulfonyl chloride]] and [[n-Butyllithium|''n''-butyllithium]]—and needs low-temperature conditions.<ref name=Brickner/><ref name=Xu/><ref name=Kaiser>{{cite journal |vauthors=Kaiser CR, Cunico W, Pinheiro AC, de Oliveira AG, Peralta MA, de Souza MV |title=Oxazolidinonas: uma nova classe de compostos no combate à tuberculose |trans-title=Oxazolidinones: a new class of compounds against tuberculosis |language=pt |journal=Revista Brasileira de Farmácia |volume=88 |issue=2 |pages=83–8 |year=2007 |url=http://www.rbfarma.org.br/images/edicoes-em-pdf/2007/RBF_V88_N2_2007/PAG83a88_OXAZOLIDINONAS.pdf |url-status=dead |archive-url=https://www.webcitation.org/67ft9fcH1?url=http://www.rbfarma.org.br/images/edicoes-em-pdf/2007/RBF_V88_N2_2007/PAG83a88_OXAZOLIDINONAS.pdf |archive-date=15 May 2012 }}</ref> Much of the high cost of linezolid has been attributed to the expense of its synthesis.<ref name=Kaiser/> A somewhat more concise and cost-effective route better suited to large-scale production was patented by Upjohn in 1998.<ref name=Barbachyn/><ref>{{US patent reference | number = 5837870 | y = 1997 | m = 03 | d = 28 | inventor = Pearlman BA, Perrault WR, Barbachyn MR, ''et al.'' | title = Process to prepare oxazolidinones}} Retrieved on 13 June 2009.</ref>

Later syntheses have included an "[[atom economy|atom-economical]]" method starting from [[D-Mannitol|<small>D</small>-mannitol]], developed by Indian pharmaceutical company [[Dr. Reddy's Laboratories|Dr. Reddy's]] and reported in 1999,<ref>{{cite journal |vauthors=Lohray BB, Baskaran S, Rao BS, Reddy BY, Rao IN |title=A short synthesis of oxazolidinone derivatives linezolid and eperezolid: A new class of antibacterials |journal=[[Tetrahedron Letters]] |volume=40 |issue=26 |pages=4855–6 |date=June 1999 |doi=10.1016/S0040-4039(99)00893-X}}</ref> and a route starting from (''S'')-glyceraldehyde acetonide (prepared from [[ascorbic acid]]), developed by a team of researchers from [[Hunan Normal University]] in [[Changsha]], [[Hunan]], China.<ref name=Xu/>  On 25 June 2008, during the 12th Annual Green Chemistry and Engineering Conference in New York, Pfizer reported the development of their "second-generation" synthesis of linezolid: a [[convergent synthesis|convergent]], [[green chemistry|green]] synthesis starting from (''S'')-[[epichlorohydrin]], with higher yield and a 56% reduction in total waste.<ref>Perrault WR, Keeler JB, Snyder WC, ''et al.'' (25 June 2008). [http://acs.confex.com/acs/green08/techprogram/P52019.HTM "Convergent green synthesis of linezolid (Zyvox)"] {{webarchive|url=https://web.archive.org/web/20110728022612/http://acs.confex.com/acs/green08/techprogram/P52019.HTM |date=28 July 2011 }}, in ''12th Annual Green Chemistry and Engineering Conference'', 24–26 June 2008, New York, NY. Retrieved on 8 June 2009.</ref>

==Resistance==
Acquired resistance to linezolid was reported as early as 1999, in two patients with severe, multidrug-resistant ''[[Enterococcus faecium]]'' infection who received the drug through a [[expanded access|compassionate use]] program.<ref name=DrugTherPerspect>{{cite journal |title=Linezolid: First of a New Drug Class for Gram-Positive Infections |journal=Drugs & Therapy Perspectives |volume=17 |issue=9 |pages=1–6 |year=2001 |url=http://www.medscape.com/viewarticle/406493 |author=[No authors listed] |doi=10.2165/00042310-200117090-00001 |s2cid=195232060 |url-status=live |archive-url=https://web.archive.org/web/20130521043752/http://www.medscape.com/viewarticle/406493 |archive-date=21 May 2013 |url-access=subscription }}<!-- not indexed in MEDLINE --> Free full text with registration at [[Medscape]].</ref> Linezolid-resistant ''[[Staphylococcus aureus]]'' was first isolated in 2001.<ref>{{cite journal  |vauthors=Tsiodras S, Gold HS, Sakoulas G, etal |title=Linezolid resistance in a clinical isolate of ''Staphylococcus aureus'' |journal=[[Lancet (journal)|The Lancet]] |volume=358 |issue=9277 |pages=207–8 |date=July 2001 |pmid=11476839 |doi=10.1016/S0140-6736(01)05410-1 |s2cid=27426801 |issn=0140-6736}}</ref>

In the United States, resistance to linezolid has been monitored and tracked since 2004 through a program named LEADER, which ({{as of|2007|lc=on}}) was conducted in 60 medical institutions throughout the country. Resistance has remained stable and extremely low—less than one-half of one percent of [[wikt:isolate|isolate]]s overall, and less than one-tenth of one percent of ''S. aureus'' samples.<ref name=autogenerated1>{{cite journal | vauthors = Jones RN, Ross JE, Castanheira M, Mendes RE | title = United States resistance surveillance results for linezolid (LEADER Program for 2007) | journal = Diagnostic Microbiology and Infectious Disease | volume = 62 | issue = 4 | pages = 416–26 | date = December 2008 | pmid = 19022153 | doi = 10.1016/j.diagmicrobio.2008.10.010 }}</ref> A similar, worldwide program—the "Zyvox Annual Appraisal of Potency and Spectrum Study", or ZAAPS—has been conducted since 2002. {{As of|2007}}, overall resistance to linezolid in 23 countries was less than 0.2%, and nonexistent among streptococci. Resistance was only found in Brazil, China, Ireland, and Italy, among [[Staphylococcus#Coagulase-negative|coagulase-negative staphylococci]] (0.28% of samples resistant), enterococci (0.11%), and ''S. aureus'' (0.03%).<ref name=ZAAPS2007>{{cite journal | vauthors = Jones RN, Kohno S, Ono Y, Ross JE, Yanagihara K | title = ZAAPS International Surveillance Program (2007) for linezolid resistance: results from 5591 Gram-positive clinical isolates in 23 countries | journal = Diagnostic Microbiology and Infectious Disease | volume = 64 | issue = 2 | pages = 191–201 | date = June 2009 | pmid = 19500528 | doi = 10.1016/j.diagmicrobio.2009.03.001 }}</ref> In the United Kingdom and Ireland, no resistance was found in staphylococci collected from [[bacteremia]] cases between 2001 and 2006,<ref>{{cite journal | vauthors = Hope R, Livermore DM, Brick G, Lillie M, Reynolds R | title = Non-susceptibility trends among staphylococci from bacteraemias in the UK and Ireland, 2001–06 | journal = The Journal of Antimicrobial Chemotherapy | volume = 62 | issue = Suppl 2 | pages = ii65–74 | date = November 2008 | pmid = 18819981 | doi = 10.1093/jac/dkn353 | doi-access = free }}</ref> although resistance in enterococci has been reported.<ref>{{cite journal | vauthors = Auckland C, Teare L, Cooke F, Kaufmann ME, Warner M, Jones G, Bamford K, Ayles H, Johnson AP | title = Linezolid-resistant enterococci: report of the first isolates in the United Kingdom | journal = The Journal of Antimicrobial Chemotherapy | volume = 50 | issue = 5 | pages = 743–6 | date = November 2002 | pmid = 12407134 | doi = 10.1093/jac/dkf246 | s2cid = 2468640 | doi-access = free }}</ref> Some authors have predicted that resistance in ''E. faecium'' will increase if linezolid use continues at current levels or increases.<ref name=Scheetz/> Nevertheless, linezolid continues to be an important antimicrobial agent with near-complete activity (0.05% resistance).<ref name=Bialvaei/>

===Mechanism===
The ''intrinsic'' resistance of most Gram-negative bacteria to linezolid is due to the activity of [[efflux (microbiology)|efflux pumps]], which [[active transport|actively]] "pump" linezolid out of the cell faster than it can accumulate.<ref name=Barbachyn/><ref>{{cite journal |vauthors=Schumacher A, Trittler R, Bohnert JA, Kümmerer K, Pagès JM, Kern WV |title=Intracellular accumulation of linezolid in ''Escherichia coli'', ''Citrobacter freundii'' and ''Enterobacter aerogenes'': role of enhanced efflux pump activity and inactivation |journal=Journal of Antimicrobial Chemotherapy |volume=59 |issue=6 |pages=1261–4 |date=June 2007 |pmid=16971414 |doi=10.1093/jac/dkl380 |doi-access=free }}</ref>

Gram-positive bacteria usually develop resistance to linezolid as the result of a [[point mutation]] known as ''G2576T'', in which a [[guanine]] base is replaced with [[thymine]] in [[base pair]] 2576 of the genes coding for 23S ribosomal RNA.<ref name=Saager>{{cite journal  |vauthors=Saager B, Rohde H, Timmerbeil BS, etal |title=Molecular characterisation of linezolid resistance in two vancomycin-resistant (VanB) ''Enterococcus faecium'' isolates using Pyrosequencing |journal=European Journal of Clinical Microbiology & Infectious Diseases |volume=27 |issue=9 |pages=873–8 |date=September 2008 |pmid=18421487 |doi=10.1007/s10096-008-0514-6 |s2cid=1085422 |issn=0934-9723}}</ref><ref name=Besier>{{cite journal |vauthors=Besier S, Ludwig A, Zander J, Brade V, Wichelhaus TA |title=Linezolid Resistance in Staphylococcus aureus: Gene Dosage Effect, Stability, Fitness Costs, and Cross-Resistances |journal=Antimicrobial Agents and Chemotherapy |volume=52 |issue=4 |pages=1570–2 |date=April 2008 |pmid=18212098 |pmc=2292563 |doi=10.1128/AAC.01098-07 }}</ref> This is the most common mechanism of resistance in staphylococci, and the only one known to date in isolates of ''E. faecium''.<ref name=Scheetz>{{cite journal |vauthors=Scheetz MH, Knechtel SA, Malczynski M, Postelnick MJ, Qi C |title=Increasing Incidence of Linezolid-Intermediate or -Resistant, Vancomycin-Resistant Enterococcus faecium Strains Parallels Increasing Linezolid Consumption |journal=Antimicrobial Agents and Chemotherapy |volume=52 |issue=6 |pages=2256–9 |date=June 2008 |pmid=18391028 |pmc=2415807 |doi=10.1128/AAC.00070-08 }}</ref> Other mechanisms have been identified in ''[[Streptococcus pneumoniae]]'' (including mutations in an RNA [[methyltransferase]] that methylates G2445 of the 23S rRNA and mutations causing increased [[gene expression|expression]] of [[ATP-binding cassette transporter|ABC transporter]] genes)<ref name=Feng2009>{{cite journal  |vauthors=Feng J, Lupien A, Gingras H, etal |title=Genome sequencing of linezolid-resistant Streptococcus pneumoniae mutants reveals novel mechanisms of resistance |journal=Genome Research |volume=19 |issue=7 |pages=1214–23 |date=May 2009 |pmid=19351617 |doi=10.1101/gr.089342.108 |issn=1088-9051 |pmc=2704432}}</ref> and in ''[[Staphylococcus epidermidis]]''.<ref>{{cite journal |vauthors=Lincopan N, de Almeida LM, Elmor de Araújo MR, Mamizuka EM |title=Linezolid resistance in ''Staphylococcus epidermidis'' associated with a G2603T mutation in the 23S rRNA gene |journal=International Journal of Antimicrobial Agents |volume= 34|issue= 3|pages= 281–2|date=April 2009 |pmid=19376688 |doi=10.1016/j.ijantimicag.2009.02.023 |issn=0924-8579|doi-access=free }}</ref><ref>{{cite journal  |vauthors=Liakopoulos A, Neocleous C, Klapsa D, etal |title=A T2504A mutation in the 23S rRNA gene responsible for high-level resistance to linezolid of ''Staphylococcus epidermidis'' |journal=Journal of Antimicrobial Chemotherapy |volume= 64|issue=1 |pages= 206–7|date=July 2009 |pmid=19429927 |doi=10.1093/jac/dkp167 |doi-access= }}</ref>

==History==
The [[2-Oxazolidone|oxazolidinone]]s have been known as [[monoamine oxidase inhibitor]]s since the late 1950s. Their antimicrobial properties were discovered by researchers at [[DuPont|E.I. duPont de Nemours]] in the 1970s.<ref name=Brickner>{{cite journal | vauthors = Brickner SJ |title=Oxazolidinone antibacterial agents |journal=[[Current Pharmaceutical Design]] |year=1996 |volume=2 |issue=2 |pages=175–94 |doi=10.2174/1381612802666220921173820 |s2cid=252456453 |url=https://books.google.com/books?id=_HFitfA4OcUC&pg=PA175|url-access=subscription }} Detailed review of the discovery and development of the whole oxazolidinone class, including information on [[chemical synthesis|synthesis]] and [[structure-activity relationship]]s.</ref> In 1978, DuPont [[patent]]ed a series of oxazolidinone derivatives as being effective in the treatment of [[bacteria]]l and [[fungus|fungal]] [[plant pathology|plant disease]]s, and in 1984, another patent described their usefulness in treating bacterial infections in [[mammal]]s.<ref name=Moellering>{{cite journal |vauthors=Moellering RC |title=Linezolid: the first oxazolidinone antimicrobial |journal=[[Annals of Internal Medicine]] |volume=138 |issue=2 |pages=135–42 |date=January 2003 |pmid=12529096 |issn=0003-4819 |doi=10.7326/0003-4819-138-2-200301210-00015 |s2cid=23689046 |url=http://memberfiles.freewebs.com/53/35/75763553/documents/Linezolid%20The%20First%20Oxazolidinone%20Antimicrobial.pdf |access-date=25 September 2019 |archive-date=14 March 2020 |archive-url=https://web.archive.org/web/20200314075925/https://memberfiles.freewebs.com/53/35/75763553/documents/Linezolid%20The%20First%20Oxazolidinone%20Antimicrobial.pdf |url-status=live }}</ref><ref name=Brickner/> In 1987, DuPont scientists presented a detailed description of the oxazolidinones as a new class of antibiotics with a novel [[mechanism of action]].<ref name=Brickner/><ref name=Slee>{{cite journal |vauthors=Slee AM, Wuonola MA, McRipley RJ, etal |title=Oxazolidinones, a new class of synthetic antibacterial agents: in vitro and in vivo activities of DuP 105 and DuP 721 |journal=[[Antimicrobial Agents and Chemotherapy]] |volume=31 |issue=11 |pages=1791–7 |date=November 1987 |pmid=3435127 |pmc=175041 |doi=10.1128/AAC.31.11.1791 |url-status=live |url=http://aac.asm.org/cgi/reprint/31/11/1791.pdf|archive-url=https://web.archive.org/web/20110611221908/http://aac.asm.org/cgi/reprint/31/11/1791.pdf |archive-date=11 June 2011 }}</ref> Early compounds were found to produce [[hepatotoxicity|liver toxicity]], however, and [[drug development|development]] was discontinued.<ref name=Livermore>{{cite journal | vauthors = Livermore DM |title=Quinupristin/dalfopristin and linezolid: where, when, which and whether to use? |journal=Journal of Antimicrobial Chemotherapy |volume=46 |issue=3 |pages=347–50 |date=September 2000 |pmid=10980159 |doi=10.1093/jac/46.3.347 |issn=0305-7453|doi-access=free }}</ref>

[[Pharmacia|Pharmacia &]] [[Upjohn]] (now part of Pfizer) started its own oxazolidinone research program in the 1990s. Studies of the compounds' [[structure–activity relationship]]s led to the development of several subclasses of oxazolidinone derivatives, with varying safety profiles and antimicrobial activity. Two compounds were considered drug candidates: [[eperezolid]] (codenamed ''PNU-100592'') and linezolid (''PNU-100766'').<ref name=Barbachyn>{{cite journal |vauthors=Barbachyn MR, Ford CW |title=Oxazolidinone structure-activity relationships leading to linezolid |journal=[[Angewandte Chemie|Angewandte Chemie International Edition in English]] |volume=42 |issue=18 |pages=2010–23 |date=May 2003 |pmid=12746812 |doi=10.1002/anie.200200528 |issn=1433-7851}}</ref><ref name=French/> In the preclinical stages of development, they were similar in safety and antibacterial activity, so they were taken to [[Phase I trial|Phase I]] [[clinical trial]]s to identify any difference in [[pharmacokinetics]].<ref name=Livermore/><ref name=Ford>{{cite journal |vauthors=Ford CW, Zurenko GE, Barbachyn MR |title=The discovery of linezolid, the first oxazolidinone antibacterial agent |journal= Current Drug Targets. Infectious Disorders|volume=1 |issue=2 |pages=181–99 |date=August 2001 |pmid=12455414 |doi=10.2174/1568005014606099 }}</ref> Linezolid was found to have a pharmacokinetic advantage—requiring only twice-daily dosage, while eperezolid needed to be given three times a day to achieve similar exposure—and therefore proceeded to further trials.<ref name=Barbachyn/> The [[Food and Drug Administration (United States)|U.S. Food and Drug Administration]] (FDA) approved linezolid on 18 April 2000.<ref>{{cite web |url=https://www.fda.gov/cder/foi/nda/2000/21130_Zyvox.htm |archive-url=https://web.archive.org/web/20080110042651/https://www.fda.gov/cder/foi/nda/2000/21130_Zyvox.htm |archive-date=10 January 2008 |title=Drug Approval Package: Zyvox |date=20 November 2001 |publisher=FDA [[Center for Drug Evaluation and Research]] |access-date=17 January 2009}} Comprehensive review of the FDA approval process. Includes detailed reviews of the chemistry and pharmacology of linezolid, correspondence between the FDA and Pharmacia & Upjohn, and administrative documents.</ref> Approval followed in Brazil (June 2000),<ref>{{cite web|author=ANVISA |url=http://www.anvisa.gov.br/legis/resol/2000/474_00re.htm |title=Resolução nº 474, de 5 de junho de 2000 |trans-title=Resolution number 474, of 5 June 2000 |language=pt |date=5 June 2000 |publisher=[[National Health Surveillance Agency]] |access-date=19 May 2009 |url-status=dead |archive-url=https://web.archive.org/web/20110719081421/http://www.anvisa.gov.br/legis/resol/2000/474_00re.htm |archive-date=19 July 2011 }}</ref> the United Kingdom (January 2001),<ref name="Zyvox SPC" /><ref name=French/> Japan and Canada (April 2001),<ref>{{cite journal |vauthors=Irinoda K, Nomura S, Hashimoto M |title=[Antimicrobial and clinical effect of linezolid (Zyvox), new class of synthetic antibacterial drug] |language=ja |journal=Nippon Yakurigaku Zasshi |volume=120 |issue=4 |pages=245–52 |date=October 2002 |pmid=12425150 |issn=0015-5691 |doi=10.1254/fpj.120.245|doi-access=free }}</ref><ref name=CanadaApproval>{{cite press release |url=http://www.docguide.com/news/content.nsf/news/917912FCF5C34DCA85256A46006E24B0 |title=Canada Approves Marketing Of Zyvoxam (Linezolid) For Gram Positive Infections |date=8 May 2001 |access-date=18 May 2009 |url-status=live |archive-url=https://web.archive.org/web/20080828012714/http://www.docguide.com/news/content.nsf/news/917912FCF5C34DCA85256A46006E24B0 |archive-date=28 August 2008 }}</ref><ref>{{cite journal |vauthors=Karlowsky JA, Kelly LJ, Critchley IA, Jones ME, Thornsberry C, Sahm DF |title=Determining Linezolid's Baseline In Vitro Activity in Canada Using Gram-Positive Clinical Isolates Collected prior to Its National Release |journal=Antimicrobial Agents and Chemotherapy |volume=46 |issue=6 |pages=1989–92 |date=June 2002 |pmid=12019122 |pmc=127260 |doi=10.1128/AAC.46.6.1989-1992.2002 |issn=0066-4804 |url=http://aac.asm.org/cgi/reprint/46/6/1989.pdf|url-status=live |archive-url=https://web.archive.org/web/20110929102627/http://aac.asm.org/cgi/reprint/46/6/1989.pdf |archive-date=29 September 2011 }}</ref> Europe (throughout 2001),<ref>{{cite press release|url=http://www2.prnewswire.com/cgi-bin/stories.pl?ACCT=104&STORY=/www/story/07-25-2001/0001540814&EDATE= |title=Pharmacia Corporation Reports 17% Increase In Second-Quarter Earnings-Per-Share Driven By 61% Increase In Pharmaceutical Earnings |publisher=Pharmacia Corporation |date=25 July 2001 |access-date=19 May 2009 |url-status=dead |archive-url=https://web.archive.org/web/20120509230639/http://www2.prnewswire.com/cgi-bin/stories.pl?ACCT=104&STORY=%2Fwww%2Fstory%2F07-25-2001%2F0001540814&EDATE= |archive-date=9 May 2012 }}</ref> and other countries in Latin America and Asia.<ref name=CanadaApproval/>

{{As of|2009}}, linezolid was the only oxazolidinone antibiotic available.<ref name=Livermore2009>{{cite journal |vauthors=Livermore DM, Mushtaq S, Warner M, Woodford N |title=Activity of oxazolidinone TR-700 against linezolid-susceptible and -resistant staphylococci and enterococci |journal=Journal of Antimicrobial Chemotherapy |volume=63 |issue=4 |pages=713–5 |date=April 2009 |pmid=19164418 |doi=10.1093/jac/dkp002 |issn=0305-7453|doi-access=free }}</ref> Other members of this class have entered development, such as [[posizolid]] (AZD2563),<ref>{{cite journal |vauthors=Howe RA, Wootton M, Noel AR, Bowker KE, Walsh TR, MacGowan AP |title=Activity of AZD2563, a Novel Oxazolidinone, against Staphylococcus aureus Strains with Reduced Susceptibility to Vancomycin or Linezolid |journal=Antimicrobial Agents and Chemotherapy |volume=47 |issue=11 |pages=3651–2 |date=November 2003 |pmid=14576139 |pmc=253812 |doi=10.1128/AAC.47.11.3651-3652.2003 |issn=0066-4804 |url=http://aac.asm.org/cgi/reprint/47/11/3651.pdf|url-status=live |archive-url=https://web.archive.org/web/20110929080102/http://aac.asm.org/cgi/reprint/47/11/3651.pdf |archive-date=29 September 2011 }}</ref> [[ranbezolid]] (RBx 7644),<ref>{{cite journal  |vauthors=Kalia V, Miglani R, Purnapatre KP, etal |title=Mode of Action of Ranbezolid against Staphylococci and Structural Modeling Studies of Its Interaction with Ribosomes |journal=Antimicrobial Agents and Chemotherapy |volume=53 |issue=4 |pages=1427–33 |date=April 2009 |pmid=19075051 |doi=10.1128/AAC.00887-08 |issn=0066-4804 |pmc=2663096}}</ref> and [[radezolid]] (RX-1741).<ref>{{cite web |url=http://www.rib-x.com/pipeline/rx_1741 |title= Rx 1741 |publisher=Rib-X Pharmaceuticals |year=2009 |access-date=17 May 2009 |archive-url=https://web.archive.org/web/20090226201337/http://www.rib-x.com/pipeline/rx_1741 <!-- Added by H3llBot --> |archive-date=26 February 2009}}</ref> In 2014, the FDA approved [[Tedizolid|tedizolid phosphate]], a second-generation oxazolidinone derivative, for acute bacterial skin and skin structure infection.<ref>{{cite web | title=Drug Approval Package: Sivextro (tedizolid phosphate) tablets NDA #205435 | website=U.S. [[Food and Drug Administration]] (FDA) | date=16 July 2014 | url=https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/205435Orig1s000TOC.cfm | access-date=29 March 2024 | archive-date=6 July 2020 | archive-url=https://web.archive.org/web/20200706103911/https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/205435Orig1s000TOC.cfm | url-status=dead }}</ref><ref>{{cite web | title=Drug Approval Package: Sivextro (tedizolid phosphate) injection NDA #205436 | website=U.S. [[Food and Drug Administration]] (FDA) | date=10 October 2014 | url=https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/205436Orig1s000TOC.cfm | access-date=29 March 2024 | archive-date=6 July 2020 | archive-url=https://web.archive.org/web/20200706064051/https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/205436Orig1s000TOC.cfm | url-status=dead }}</ref>

==Society and culture==

===Economics===
{{further|Pharmacoeconomics|Disease burden}}

Linezolid was quite expensive in 2009; a course of treatment may cost one or two thousand U.S. dollars for the drug alone,<ref name=Lexi-Comp>{{cite web |url=http://www.merck.com/mmpe/lexicomp/linezolid.html |title=Linezolid |date=August 2008 |author=Lexi-Comp |work=[[Merck Manual of Diagnosis and Therapy|The Merck Manual Professional]] |url-status=live |archive-url=https://web.archive.org/web/20090426220140/http://www.merck.com/mmpe/lexicomp/linezolid.html |archive-date=26 April 2009 }} Retrieved on 14 May 2009.</ref> not to mention other costs (such as those associated with hospital stay). With the medication becoming generic the price has decreased. In India as of 2015 a month of linezolid, as would be used to treat tuberculosis cost about US$60.<ref name=WHO2015Use/>

However, because intravenous linezolid may be switched to an oral formulation (tablets or oral solution) without jeopardizing efficacy, people may be discharged from hospital relatively early and continue treatment at home, whereas home treatment with injectable antibiotics may be impractical.<ref name=Grau2008/> Reducing the [[length of stay|length of hospital stay]] reduces the overall cost of treatment, even though linezolid may have a higher acquisition cost—that is, it may be more expensive—than comparable antibiotics.

Studies have been conducted in several countries with different [[health care system]] models to assess the [[cost-effectiveness analysis#CEA in pharmacoeconomics|cost-effectiveness]] of linezolid compared to glycopeptides such as vancomycin or teicoplanin. In most countries, linezolid was more cost-effective than comparable antibiotics for the treatment of hospital-acquired pneumonia and complicated skin and skin structure infections, either due to higher cure and survival rates or lower overall treatment costs.<ref name=Grau2008>{{update after|2020|6|13}}{{cite journal | vauthors = Grau S, Rubio-Terrés C | title = Pharmacoeconomics of linezolid | journal = Expert Opinion on Pharmacotherapy | volume = 9 | issue = 6 | pages = 987–1000 | date = April 2008 | pmid = 18377341 | doi = 10.1517/14656566.9.6.987 | s2cid = 3005291 }}</ref>

In 2009, Pfizer paid $2.3&nbsp;billion and entered a [[corporate integrity agreement]] to settle charges that it had misbranded and illegally promoted four drugs, and caused false claims to be submitted to government healthcare programs for uses that had not been approved by the United States Food and Drug Administration.<ref>{{cite news |url=http://news.bbc.co.uk/2/hi/business/8234533.stm |title=Pfizer agrees record fraud fine |work=BBC News |date=2 September 2009 |access-date=12 September 2009 |url-status=live |archive-url=https://web.archive.org/web/20090908011344/http://news.bbc.co.uk/2/hi/business/8234533.stm |archive-date=8 September 2009 }}</ref> $1.3&nbsp;billion was paid to settle criminal charges of illegally marketing the anti-inflammatory [[valdecoxib]], while $1&nbsp;billion was paid in civil fines regarding illegal marketing of three other drugs, including Zyvox.<ref>{{cite news |url=https://www.nytimes.com/2009/09/03/business/03health.html |title=Pfizer pays $2.3 billion to settle marketing case | vauthors = Harris G |date=2 September 2009 |work=[[The New York Times]] |access-date=12 September 2009 |url-status=live |archive-url=https://web.archive.org/web/20110822013720/http://www.nytimes.com/2009/09/03/business/03health.html |archive-date=22 August 2011 }}</ref>

===Brand names===
{| class="wikitable mw-collapsible mw-collapsed" style="width:100%"
|+ List of [[trade name]]s for linezolid<ref name=Name2018Int>{{cite web |title=Linezolid |url=https://www.drugs.com/international/linezolid.html |website=Drugs.com |access-date=29 December 2018 |language=en |archive-date=29 December 2018 |archive-url=https://web.archive.org/web/20181229171319/https://www.drugs.com/international/linezolid.html |url-status=live }}</ref>
|-
|A||Amizole 500 (Kenya), Anozilad (Poland), Antizolid (Greece), Arlid (India), Arlin (Bangladesh), Averozolid & Debacozoline (Egypt)
|-
|-
|B||
|-
|C||
|-
|D||Dilizolen (Poland, Slovakia, Netherlands, Bulgaria)
|-
|E||Entavar (India)
|-
|F||
|-
|G||Grampolid (Netherlands), Grampolyve (Netherlands), Gramposimide (Poland, Netherlands), Grampoxid (Netherlands)
|-
|H||
|-
|I||
|-
|J||
|-
|K||
|-
|L||Linzolid (Bangladesh), Lidobact (Netherlands), Linez (Bangladesh, Egypt), Linezolid Accord (Netherlands), Linezolid Amneal (Netherlands), Linezolid Betapharm (Netherlands), Linezolid Farmaprojects (Netherlands), Linezolid Fresenius Kabi (Netherlands), Linezolid GNP (Egypt), Linezolid Hetero (Netherlands), Linezolid Kabi (Croatia, Poland), Linezolid Mylan (Netherlands), Linezolid Pfizer (Netherlands), Linezolid Pliva (Croatia), Linezolid Polpharma (Netherlands, Poland), Linezolid Richet (Argentina), Linezolid Sandoz (Belgium, Switzerland, Netherlands, Slovakia, Estonia, Croatia, Poland), Linezolid Teva (Netherlands, Romania), Linezolid Zentiva (Poland), Linezolida Teva (Portugal), Linezone (Turkey), Linid (India), Linosept (India), Linozid (Bangladesh), Linxyd (Netherlands), Linzowin (India), Litrecan (Argentina), Livegramide (Netherlands), Lizbid (India), Lizemox (India), Lizolid (India, Vietnam), Lizoliden (Netherlands), Lizomac (India), Lizomed (India), Lizorex (India), Lizox (Netherlands), Lorezogram (Netherlands), Lynvox (Netherlands), Lynz (Croatia)
|-
|M||
|-
|N||Natlinez (Netherlands)
|-
|O||
|-
|P||Pneumolid (Croatia, Netherlands, Poland, Romania, Bulgaria)
|-
|Q||
|-
|R||Ralinz (India), Respenzo (Egypt)
|-
|S||Synzolid (Netherlands)
|-
|T||
|-
|U||
|-
|V||Voxazoldin (Egypt)
|-
|W||
|-
|X||
|-
|Y||
|-
|Z||Zenix (Bosnia and Herzegovina, Serbia), Zizolid (Turkey), Zodlin (India), Zolinid (Bulgaria), Zyvox (Georgia, Chile, Argentina, Australia, China, Ecuador, Egypt, United Kingdom, Hong Kong, Indonesia, Ireland, South Korea, Malta, Malaysia, New Zealand, Philippines, Singapore, Thailand, Taiwan, Japan, United States), Zyvoxam (Canada), Zyvoxid (Israel, Austria, Belgium, Bulgaria, Switzerland, Czech Republic, Denmark, Estonia, Spain, Finland, France, Greece, Germany, Croatia, Iceland, Lithuania, Latvia, Netherlands, Norway, Portugal, Romania, Sweden, Slovakia, Tunisia, Turkey, South Africa, Poland, Italy, Bosnia and Herzegovina)
|-
|}
{| class="wikitable mw-collapsible mw-collapsed" style="width:100%"
|+ List of [[trade name]]s for linezolid-containing products<ref name=Name2018Int/>
|-
! scope="col" | Generic Combination
! scope="col" | Brand Name
|-
| linezolid and cefixime || Zifi-Turbo (India)
|}

==References==
{{reflist}}

{{Other antibacterials}}
{{Monoamine metabolism modulators}}
{{Portal bar|Medicine}}

[[Category:2000 introductions]]
[[Category:American inventions]]
[[Category:Anti-tuberculosis drugs]]
[[Category:Fluoroarenes]]
[[Category:Hepatotoxins]]
[[Category:Monoamine oxidase inhibitors]]
[[Category:4-Morpholinyl compounds]]
[[Category:Oxazolidinone antibiotics]]
[[Category:Drugs developed by Pfizer]]
[[Category:World Health Organization essential medicines]]
[[Category:Wikipedia medicine articles ready to translate]]