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| {{drugbox
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| | IUPAC_name = ''N''-<nowiki>[[</nowiki>3-(3-fluoro-4-morpholinophenyl)-<br />2-oxooxazolidin-5-yl<nowiki>]</nowiki>methyl<nowiki>]</nowiki>acetamide
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| | image = Linezolid_Structure.png
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| | CAS_number = 165800-03-3
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| | ATC_prefix = J01
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| | ATC_suffix = XX08
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| | PubChem = 441401
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| | DrugBank = APRD01073
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| | C=16 | H=20 | F=1 | N=3 | O=4
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| | molecular_weight = 337.346 g/mol
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| | bioavailability = ~100% (oral)
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| | protein_bound = 31%
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| | metabolism = Hepatic 50–70%
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| | elimination_half-life = 4.2–5.4 hours
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| | excretion = Renal 80–85%
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| | pregnancy_category = C <small>([[Australia|Au]])</small>, C <small>([[United States|U.S.]])</small>
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| | legal_status = S4 <small>(Au)</small>, POM <small>([[United Kingdom|UK]])</small>, ℞-only <small>(U.S.)</small>
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| | routes_of_administration = [[Intravenous|IV]], oral
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| }}
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| {{SI}}
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| ==Overview==
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| '''Linezolid''' ([[International Nonproprietary Name|INN]]) ([[International Phonetic Alphabet|IPA]]: {{IPA|[lɪnɛˈzəlɪd]}}) is a synthetic [[antibiotic]], the first of the [[oxazolidinone]] class, used for the treatment of infections caused by multi-resistant [[bacteria]] including [[streptococcus]] and [[methicillin-resistant Staphylococcus aureus|methicillin-resistant ''Staphylococcus aureus'']] (MRSA). It is marketed under the trade name '''Zyvox''' (or '''Zyvoxid''' in [[Europe]]) ([[Pfizer, Inc.|Pfizer]]).
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| It was the first commercially available [[oxazolidinone]] antibiotic and is usually reserved for the treatment of serious [[bacteria|bacterial]] infections where older antibiotics have failed due to [[antibiotic resistance]]. Conditions such as skin infections or nosocomial [[pneumonia]] where [[methicillin]] or [[penicillin]] resistance is found are indicators for linezolid use. Compared to the older antibiotics it is quite expensive.
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| The drug works by inhibiting the initiation of bacterial protein synthesis. Initially there was hope that bacteria would be unable to develop resistance to it. However, in 2001 ''[[Staphylococcus aureus]]'' was first identified as being resistant to linezolid.<ref>Tsiodras S, Gold HS, Sakoulas G, et al. Linezolid resistance in a clinical isolate of Staphylococcus aureus. Lancet. 2001 Jul 21;358(9277):207-8.</ref> Linezolid is effective against [[gram-positive]] pathogens, notably ''[[Enterococcus faecium]]'', ''Staphylococcus aureus'', ''[[Streptococcus agalactiae]]'', ''[[Streptococcus pneumoniae]]'', and ''[[Streptococcus pyogenes]]''. It has almost no effect on gram-negative bacteria and is only [[bacteriostatic]] against most [[Enterococcus]] species.
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| Linezolid has been used to treat [[Tuberculosis treatment|tuberculosis]].<ref name="Lippea2006">{{cite journal | journal=J Infect | volume=52 | issue=2 | year=2006 | pages=92–6 | doi=10.1016/j.jinf.2005.04.007 | title=Efficacy and safety of linezolid in multidrug resistant tuberculosis (MDR-TB)—a report of ten cases | author=von der Lippea B, Sandvenb P, Brubakk O. }}</ref>
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| The oxazolidinone class was discovered by researchers at E.I. duPont de Nemours and reported in [[1987]]. [[Upjohn]] developed linezolid (Upjohn is now part of [[Pfizer]]) and [[Food and Drug Administration]] (FDA) approval was granted in [[April]] of [[2000]]. It is sold in the U.S. under the tradename '''Zyvox''' in either tablet form, oral suspension powder, or in an inactive medium for intravenous injection.
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| ==Mechanism of Action==
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| Linezolid works on the initiation of protein synthesis. It does this by stopping the [[30S]] and [[50S]] subunit from binding together. Linezolid binds on the 23S portion of the 50S subunit close to the peptidyl transferase and [[chloramphenicol]] binding sites. This then stops the interaction with the 30S subunit.
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| ==Dosing==
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| The adult dose of linezolid is 600mg twice daily orally or intravenously for a maximum of 14 days. The dose in children is 10mg/kg orally or intravenously three times a day for a maximum of 14 days.
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| Linezolid has been used in the treatment of [[Tuberculosis treatment|tuberculosis]] (in combination with other drugs).<ref name="Lippea2006"/> The optimal dose for use in tuberculosis is not known. In adults, 600mg daily<ref name="Park2006">{{cite journal | journal=J Antimicrob Chemother | year=2006 | volume=58 | issue=3 | pages=701–4 | title=Efficacy and tolerability of daily-half dose linezolid in patients with intractable multidrug-resistant tuberculosis | author=Park IN, Hong SB, Oh YM, ''et al.'' | id=PMID 16857689 }}</ref> or 600mg twice daily<ref>{{cite journal | journal=J Antimicrob Chemother | year=2005 | volume=56 | issue=1 | pages=180–5
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| | title=Linezolid for the treatment of multidrug-resistant tuberculosis | author=Fortun J, Martin-Davila P, Navas E, ''et al.'' | doi=10.1093/jac/dki148
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| }}</ref> have both been used to good effect. The treatment often needs to be continued for many months and the rate of adverse effects is high.<ref name="Park2006"/> The lower dose is not associated with a lower rate of adverse effects.<ref name="Park2006"/>
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| ==Adverse effects==
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| Side effects include rashes, loss of appetite, diarrhea, nausea, constipation and fever. A small number of patients will incur a severe allergic reaction, or [[tinnitus]], or [[pseudomembranous colitis]]. [[Thrombocytopenia]] is uncommon in patients who receive linezolid for 14 days or less (the manufacturer's recommendation), but in patients who receive longer courses, or who have renal failure, the rate is much higher.<ref>{{cite journal | author=Lin Y-H, Wu V-C, Tsai I-J, ''et al.'' | title=High frequency of linezolid-associated thrombocytopenia among patients with renal insufficiency | journal=Int J Antimicrob Agents | vol=28 | issue=4 | pages=345–51 | doi=10.1016/j.ijantimicag.2006.04.017 }}</ref> The anemia and thrombocytopenia caused by linezolid are not prevented by concurrent administration of [[pyridoxine]] 125mg daily.<ref>{{cite journal | title=No effect of pyridoxine on the incidence of myelosuppression during prolonged linezolid treatment | author=Plachouras D, Giannitsioti E, Athanassia S, ''et al.'' | journal=Clin Infect Dis | year=2006 | volume=43 | issue=9 | pages=e89–91 | url=http://www.journals.uchicago.edu/CID/journal/issues/v43n9/39777/39777.web.pdf}}</ref>
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| Linezolid is a weak [[monoamine oxidase inhibitor]] (MAOI) and cannot be used with [[tyramine]] containing foods or [[pseudoephedrine]].
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| Linezolid is toxic to [[mitochondria]] (probably because of the similarity between mitochondrial and bacterial [[ribosome]]s). Signs of mitochondrial toxicity include [[lactic acidosis]] and [[peripheral neuropathy]].<ref>{{cite journal | author=Soriano A, Miró O, Mensa J|title=Mitochondrial Toxicity Associated with Linezolid|journal=N Engl J Med | volume=353 | issue=21 | pages=2305–6 }}</ref> Painful sensory neuropathy (PMID: 17766431).
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| ==External link==
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| * http://www.zyvox.com/
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| * http://www.fda.gov/cder/drug/infopage/linezolid/default.htm
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| ==References==
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| <references/>
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| {{Other antibacterials}}
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| [[Category:Antibiotics]]
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| [[Category:Organofluorides]]
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| [[de:Linezolid]]
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| [[es:Linezolid]]
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| [[fr:Linézolide]]
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| [[he:לינזוליד]]
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| [[hu:Linezolid]]
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| [[ja:リネゾリド]]
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