Editing Linezolid (section)

===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/>