Editing Linezolid (section)

==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
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| 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/>