Linezolid

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Linezolid

Clinical data

Pronunciation /lnzld/ or /lnezld/, li-NEZ--lid

Trade names Zyvox, Zyvoxid, others

AHFS/Drugs.com Monograph

MedlinePlus a602004

License data US FDA: Linezolid

Pregnancy AU: C
category
US: C (Risk not ruled out)

Routes of intravenous infusion, by mouth

administration

ATC code J01XX08 (WHO)

Legal status

Legal status AU: S4 (Prescription only)

 CA: -only

UK: POM (Prescription only)

US: -only

Pharmacokinetic data

Bioavailability ~100% (oral)

Protein binding Low (31%)

Metabolism liver (5070%, CYPnot involved)

Biological half-life 4.25.4 hours (shorter in children)

Excretion non-kidney, kidney, and fecal

Identifiers

IUPAC name[show]

CAS Number 165800-03-3

PubChem CID 441401

DrugBank DB00601

ChemSpider 390139

UNII ISQ9I6J12J

KEGG D00947

ChEMBL CHEMBL126

NIAID ChemDB 070944

ECHA InfoCard 100.121.520

Chemical and physical data

Formula C16H20FN3O4

Molar mass 337.346 g/mol

3D model (JSmol) Interactive image

SMILES[show]

InChI[show]

(what is this?) (verify)

Linezolid is an antibiotic used for the treatment of infections caused by Gram-positive bacteria that
are resistant to other antibiotics.[1][2] Linezolid is active against most Gram-positive bacteria that
cause disease, including streptococci, vancomycin-resistant enterococci (VRE), and methicillin-
resistant Staphylococcus aureus (MRSA).[3] 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.[2][4] It is used either by injection into a vein or by mouth.[2] Linezolid is a member
of the oxazolidinone class of medications.[2]
When given for short periods, linezolid is a relatively safe antibiotic.[1] It can be used in people of all
ages and in people with liver disease or poor kidney function. Common side effects with short-term
use include headache, diarrhea, rash, and nausea.[2] Serious side effects may include serotonin
syndrome, bone marrow suppression, and high blood lactate levels, particularly when used for more
than two weeks.[2][5] If used for longer periods still, it may cause sometimes irreversible nerve
damage including optic nerve damage.[5]
As a protein synthesis inhibitor, it affects the ability of bacteria to produce protein.[6] This either stops
growth or results in bacterial death.[2] Although many antibiotics work this way, the exact mechanism
of action of linezolid appears to be unique in that it blocks the start of protein production, rather than
one of the later steps.[6] As of 2014 bacterial resistance to linezolid has remained low.[7]
Linezolid was discovered in the mid 1990s and was approved for commercial use in 2000.[8][9] It is on
the World Health Organization's List of Essential Medicines, the most effective and safe medicines
needed in a health system.[10] Linezolid is available as a generic medication.[2] The wholesale cost in
the developing world is about US$ 2.90 USD per day[11] while that in the United States as of 2016 is
about US$13.79 per day.[12] It appears to be more cost-effective than alternatives such
as vancomycin, mostly because of the ability to switch from intravenous use to administration by
mouth sooner.[13]

Contents
[hide]

1Medical uses
o 1.1Skin and soft tissue infections
o 1.2Pneumonia
o 1.3Other
o 1.4Specific populations
o 1.5Spectrum of activity
2Adverse effects
o 2.1Long-term use
3Interactions
4Pharmacology
o 4.1Pharmacokinetics
o 4.2Mechanism of action
5Chemistry
o 5.1Synthesis
6Resistance
o 6.1Mechanism
7History
8Society and culture
o 8.1Economics
o 8.2Brand names
9References

Medical uses[edit]
The main use of linezolid is the treatment of severe infections caused by Gram-positive bacteria that
are resistant to other antibiotics; it should not be used against bacteria that are sensitive to drugs
with a narrower spectrum of activity, such as penicillins and cephalosporins. 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.[14][15]
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 faecium infections,
with or without 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 infections (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.[3] The
manufacturer advises against the use of linezolid for community-acquired pneumonia
or uncomplicated skin and soft tissue infections caused by MRSA.[3] In the United Kingdom,
pneumonia and cSSSIs are the only indications noted in the product labeling.[16]
Linezolid appears to be as safe and effective for use in children and newborns as it is in adults.[17]
Skin and soft tissue infections[edit]
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 antibiotics in the
treatment of skin and soft tissue infections (SSTIs) caused by Gram-positive bacteria,[18] and smaller
studies appear to confirm its superiority over teicoplanin in the treatment of all serious Gram-positive
infections.[19]
In the treatment of diabetic foot infections, linezolid appears to be cheaper and more effective than
vancomycin.[20] 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.[21][22] 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.[23]
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.[22][24]
Pneumonia[edit]
No significant difference appears in treatment success rates between linezolid, glycopeptides, or
appropriate beta-lactam antibiotics in the treatment of pneumonia.[18] Clinical guidelines 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.[25] The guidelines of the British Thoracic Society do not recommend it as
first-line treatment, but rather as an alternative to vancomycin.[26] Linezolid is also an acceptable
second-line treatment for community-acquired pneumococcal pneumonia when penicillin resistance
is present.[25]
U.S. guidelines recommend either linezolid or vancomycin as the first-line treatment for hospital-
acquired (nosocomial) MRSA pneumonia.[27] 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.[22] Regardless, linezolid's
advantages include its high bioavailability (because it allows easy switching to oral therapy), and the
fact that poor kidney function is not an obstacle to use (whereas achieving the correct dosage of
vancomycin in patients with renal insufficiency is very difficult).[27]
Other[edit]

This echocardiogram shows vegetations on the tricuspid valve(white arrow) caused by infective endocarditis.
The patient received conventional treatment, with ampicillin, imipenem, and glucocorticoids, and recovered fully
after heart surgery.[28]

It is traditionally believed that so-called "deep" infectionssuch as osteomyelitis or infective

endocarditisshould be treated with bactericidal antibiotics, not bacteriostatic ones. Nevertheless,
preclinical studies were conducted to assess the efficacy of linezolid for these infections,[29] 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.[30][31] Results in the treatment of
enterococcal endocarditis have varied, with some cases treated successfully and others not
responding to therapy.[32][33][34][35][36][37] 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.[38][39][40][41][42][43]
In combination with other drugs, linezolid has been used to treat tuberculosis.[44] 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.[45][46] There is not enough reliable evidence of efficacy and safety to support this
indication as a routine use.[17]
Linezolid has been studied as an alternative to vancomycin in the treatment of febrile neutropenia in
cancer patients when Gram-positive infection is suspected.[47] 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 injected directly into the eye.[22]
Infections of the central nervous system[edit]
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.[48][49] 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 infectionincluding meningitiscaused 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.[50][51] 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.[52] 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).[53]
Catheter-related infections[edit]
In March 2007, the FDA reported the results of a randomized, open-label, phase III clinical trial
comparing linezolid to vancomycin in the treatment of 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.[54] The
study itself was published in January 2009.[55]
Linezolid was associated with significantly 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.[54][55] 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.[54]
Specific populations[edit]
In adults and children over the age of 12, linezolid is usually given every 12 hours, whether orally or
intravenously.[48][56] In younger children and infants, it is given every eight hours.[57] No dosage
adjustments are required in the elderly, in people with mild-to-moderate liver failure, or in those with
impaired kidney function.[58] In people requiring hemodialysis, care should be taken to give linezolid
after a session, because dialysis removes 3040% of a dose from the body; no dosage adjustments
are needed in people undergoing continuous hemofiltration,[58] although more frequent administration
may be warranted in some cases.[17] According to one study, linezolid may need to be given more
frequently than normal in people with burns affecting more than 20% of body area, due to increased
nonrenal clearance of the drug.[59]
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.[3] It also passes into breast milk, although
the clinical significance of this (if any) is unknown.[60]
Spectrum of activity[edit]
Scanning electron micrographs of vancomycin-resistant Enterococcus(top) and methicillin-
resistant Staphylococcus aureus (bottom; false colors)

Linezolid is effective against all clinically important Gram-positive bacteriathose whose cell
wall contains a thick layer of peptidoglycan and no outer membranenotably Enterococcus
faecium and Enterococcus faecalis (including vancomycin-resistant enterococci), Staphylococcus
aureus (including methicillin-resistant Staphylococcus aureus, MRSA), Streptococcus
agalactiae, Streptococcus pneumoniae, Streptococcus pyogenes, the viridans group
streptococci, Listeria monocytogenes, and Corynebacterium species (the latter being among the
most susceptible to linezolid, with minimum inhibitory concentrations routinely below
0.5 mg/L).[3][48][61] Linezolid is also highly active in vitro against several mycobacteria.[48] 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.[62]
Linezolid is considered bacteriostatic against most organismsthat is, it stops their growth and
reproduction without actually killing thembut has some bactericidal (killing) activity against
streptococci.[3][63] 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 toxins by
staphylococci and streptococci.[29] It also has a post-antibiotic effect lasting one to four hours for most
bacteria, meaning that bacterial growth is temporarily suppressed even after the drug is
discontinued.[17]
Gram-negative bacteria[edit]
Linezolid has no clinically significant effect on most Gram-negative bacteria. Pseudomonas and
the Enterobacteriaceae, for instance, are not susceptible.[63] In vitro, it is active against Pasteurella
multocida,[3][64] Fusobacterium, Moraxella catarrhalis, Legionella, Bordetella, and Elizabethkingia
meningoseptica, and moderately active (having a minimum inhibitory concentration for 90% of
strains of 8 mg/L) against Haemophilus influenzae.[60][63] It has also been used to great effect as a
second-line treatment for Capnocytophaga infections.[50][65]
Comparable antibiotics[edit]
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.[1][17]Other comparable antibiotics include teicoplanin (trade name
Targocid, a glycopeptide like vancomycin), quinupristin/dalfopristin (Synercid, a combination of
two streptogramins, not active against E. faecalis),[66] and daptomycin(Cubicin, a lipopeptide), and
some agents still being developed, such as ceftobiprole, dalbavancin, and telavancin. Linezolid is
the only one that can be taken by mouth.[17] In the future, oritavancin and iclaprim may be useful oral
alternatives to linezolidboth are in the early stages of clinical development.[17]

Adverse effects[edit]
When used for short periods, linezolid is a relatively safe drug.[1] Common 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 (111%), nausea (310%), vomiting (14%), rash (2%),
constipation (2%), altered taste perception (12%), and discoloration of the tongue (0.2
1%).[58] Fungal infections such as thrush and vaginal candidiasis may also occur as linezolid
suppresses normal bacterial flora and opens a niche for fungi (so-called antibiotic
candidiasis).[58] Less common (and potentially more serious) adverse effects include allergic
reactions, pancreatitis, and elevated transaminases, which may be a sign of liver
damage.[58][67] Unlike some antibiotics, such as erythromycin and the quinolones, linezolid has no
effect on the QT interval, a measure of cardiac electrical conduction.[67][68] Adverse effects in children
are similar to those that occur in adults.[68]
Like nearly all antibiotics, linezolid has been associated with Clostridium difficile-associated
diarrhea (CDAD) and pseudomembranous colitis, although the latter is uncommon, occurring in
about one in two thousand patients in clinical trials.[58][67][68][69] C. difficile appears to be susceptible to
linezolid in vitro, and linezolid was even considered as a possible treatment for CDAD.[70]
Long-term use[edit]
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 significantly more frequently with linezolid than with glycopeptides or beta-lactams.[18]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.[67][71] A 2004 case report suggested
that pyridoxine (a form of vitamin B6) could reverse the anemia and thrombocytopenia caused by
linezolid,[72] but a later, larger study found no protective effect.[73]
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.[74] Chemotherapy drugs associated with CIPN include thalidomide, the epothilones such
as ixabepilone,
the vinca alkaloids vincristine and vinblastine,[75][76][77] the taxanes paclitaxel and docetaxel,
the proteasome inhibitors such as bortezomib, and the platinum-based
drugs cisplatin, oxaliplatin and carboplatin.[74][78][79] and optic neuropathy, which is most common after
several months of treatment and may also be irreversible.[80][81][82][83][84] Although the mechanism of
injury is still poorly understood, mitochondrial toxicity has been proposed as a cause;[85][86] linezolid is
toxic to mitochondria, probably because of the similarity between mitochondrial and
bacterial ribosomes.[87] Lactic acidosis, a potentially life-threatening buildup of lactic acid in the body,
may also occur due to mitochondrial toxicity.[85] Because of these long-term effects, the manufacturer
recommends weekly complete blood counts during linezolid therapy to monitor for possible bone
marrow suppression, and recommends that treatment last no more than 28 days.[3][67] 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 lactate levels, for
early detection of lactic acidosis; a review of all medications taken by the patient, interrupting the use
of those that may interact with linezolid; and periodic eye and neurological exams in patients set to
receive linezolid for longer than four weeks.[88]
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).[48] There have also been postmarketing reports of seizures, and, as
of 2009, a single case each of Bell's palsy(paralysis of the facial nerve) and kidney toxicity.[68]
Interactions[edit]
Linezolid is a weak 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 serotonergic drugs. There have been postmarketing
reports of serotonin syndrome when linezolid was given with or soon after the discontinuation of
serotonergic drugs, particularly selective serotonin reuptake inhibitors such
as paroxetine and sertraline.[67][89][90][91] It may also enhance the blood pressure-increasing effects
of sympathomimetic drugs such as pseudoephedrine or phenylpropanolamine.[48][92] It should also not
be given in combination with pethidine (meperidine) under any circumstance due to the risk
of serotonin syndrome.
Linezolid does not inhibit or 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.[3]

Pharmacology[edit]
Pharmacokinetics[edit]

Major metabolites of linezolid

One of the advantages of linezolid is its high bioavailability (close to 100%) when given by mouth:
the entire dose reaches the bloodstream, as if it had been given intravenously. 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.[56] Taking linezolid with food somewhat slows its absorption, but the area
under the curve is not affected.[17]
Linezolid has low plasma protein binding (approximately 31%, but highly variable) and an apparent
volume of distribution at steady state of around 4050 liters.[58] Peak serum concentrations (Cmax) are
reached one to two hours after administration of the drug. Linezolid is readily distributed to all tissues
in the body apart from bone matrix and white adipose tissue.[29] Notably, the concentration of linezolid
in the epithelial lining fluid of the lower respiratory tract is at least equal to, and often higher than,
that achieved in serum (some authors have reported bronchial fluid concentrations up to four times
higher than serum concentrations), which may account for its efficacy in treating
pneumonia. Cerebrospinal fluid (CSF) concentrations vary; peak CSF concentrations are lower than
serum ones, due to slow diffusion across the bloodbrain barrier, and trough concentrations in the
CSF are higher for the same reason.[17] The average half-life is three hours in children, four hours in
teenagers, and five hours in adults.[3]
Linezolid is metabolized in the liver, by oxidation of the morpholine ring, without involvement of
the cytochrome P450 system. This metabolic pathway leads to two major inactive metabolites (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.[93] 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.[3][93][94]
Mechanism of action[edit]
Further information: Protein biosynthesis and Translation (genetics) Basic mechanisms

Simplified schematic of mRNA translation. Linezolid occupies the A site (at center) and prevents tRNA from
binding.

The oxazolidinones are protein synthesis inhibitors: they stop the growth and reproduction of
bacteria by disrupting translation of messenger RNA (mRNA) into proteins in the ribosome. Although
its mechanism of action is not fully understood,[95] linezolid appears to work on the first step of protein
synthesis, initiation, unlike most other protein synthesis inhibitors, which inhibit elongation.[6][56]
It does so by preventing the formation of the initiation complex, composed of
the 30S and 50S subunits of the ribosome, tRNA, and mRNA. Linezolid binds to the 23S portion of
the 50S subunit (the center of peptidyl transferaseactivity),[96] close to the binding
sites 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.[17][48]
In 2008, the crystal structure of linezolid bound to the 50S subunit of a ribosome from
the archaean Haloarcula marismortui was elucidated by a team of scientists from Yale
University and deposited in the Protein Data Bank.[97]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 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.[98]

Chemistry[edit]
At physiological pH, linezolid exists in an uncharged state. It is moderately water-soluble
(approximately 3 mg/mL), with a logP of 0.55.[17]

Numbered structure of linezolid, showing the pharmacophore required for good activity (in blue) and desirable
structural features (in orange).

The oxazolidinone pharmacophorethe chemical "template" essential for antimicrobial activity

consists of a 1,3-oxazolidin-2-one moiety with an aryl group at position 3 and an S-methyl group,
with another substituent attached to it, at position 5 (the R-enantiomers of all oxazolidinones are
devoid of antibiotic properties).[99] 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 isosteric groups are used. A fluorine atom at the 3 position practically
doubles in vitro and in vivo activity, and the electron-donating nitrogen atom in the morpholine ring
helps maintain high antibiotic potency and an acceptable safety profile.[29][99]
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
chlorothiophene, and missing the fluorine atom). However this similarity appears to carry no clinical
significance.[100]
Synthesis[edit]
Linezolid is a completely 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-lactams, which are semisynthetic). Many approaches are available for oxazolidinone
synthesis, and several routes for the synthesis of linezolid have been reported in the chemistry
literature.[99][101] Despite good yields, the original method (developed by Upjohn for pilot plant-scale
production of linezolid and eperezolid) is lengthy, requires the use of expensive chemicalssuch
as palladium on carbon and the highly sensitive reagents methanesulfonyl chloride and n-
butyllithiumand needs low-temperature conditions.[99][101][102] Much of the high cost of linezolid has
been attributed to the expense of its synthesis.[102] A somewhat more concise and cost-effective route
better suited to large-scale production was patented by Upjohn in 1998.[29][103]
Later syntheses have included an "atom-economical" method starting from D-mannitol, developed by
Indian pharmaceutical company Dr. Reddy's and reported in 1999,[104] and a route starting from (S)-
glyceraldehyde acetonide (prepared from vitamin C), developed by a team of researchers
from Hunan Normal University in Changsha, Hunan, China.[101] On June 25, 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, green synthesis starting from (S)-
epichlorohydrin, with higher yield and a 56% reduction in total waste.[105]

Resistance[edit]
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 compassionate
use program.[63] Linezolid-resistant Staphylococcus aureus was first isolated in 2001.[106]
In the United States, resistance to linezolid has been monitored and tracked since 2004 through a
program named LEADER, which (as of 2007) was conducted in 60 medical institutions throughout
the country. Resistance has remained stable and extremely lowless than one-half of one percent
of isolates overall, and less than one-tenth of one percent of S. aureus samples.[107] A similar,
worldwide programthe "Zyvox Annual Appraisal of Potency and Spectrum Study", or ZAAPShas
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 coagulase-negative staphylococci (0.28% of samples resistant), enterococci (0.11%),
and S. aureus (0.03%).[108] In the United Kingdom and Ireland, no resistance was found in
staphylococci collected from bacteremia cases between 2001 and 2006,[109] although resistance in
enterococci has been reported.[110] Some authors have predicted that resistance in E. faecium will
increase if linezolid use continues at current levels or increases.[111]
Mechanism[edit]
The intrinsic resistance of most Gram-negative bacteria to linezolid is due to the activity of efflux
pumps, which actively "pump" linezolid out of the cell faster than it can accumulate.[29][112]
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.[113][114] This is the most common mechanism of resistance in staphylococci,
and the only one known to date in isolates of E. faecium.[111] 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 expression of ABC
transporter genes)[115] and in Staphylococcus epidermidis.[116][117]

History[edit]
The oxazolidinones have been known as monoamine oxidase inhibitors since the late 1950s. Their
antimicrobial properties were discovered by researchers at E.I. duPont de Nemours in the
1970s.[99] In 1978, DuPont patented a series of oxazolidinone derivatives as being effective in the
treatment of bacterial and fungal plant diseases, and in 1984, another patent described their
usefulness in treating bacterial infections in mammals.[48][99] In 1987, DuPont scientists presented a
detailed description of the oxazolidinones as a new class of antibiotics with a novel mechanism of
action.[99][118] Early compounds were found to produce liver toxicity, however, and development was
discontinued.[66]
Pharmacia & Upjohn (now part of Pfizer) started its own oxazolidinone research program in the
1990s. Studies of the compounds' structureactivity relationships 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).[29][67] In the preclinical stages of development, they were similar in safety and
antibacterial activity, so they were taken to Phase Iclinical trials to identify any difference
in pharmacokinetics.[66][119] Linezolid was found to have a pharmacokinetic advantagerequiring only
twice-daily dosage, while eperezolid needed to be given three times a day to achieve similar
exposureand therefore proceeded to further trials.[29] The U.S. Food and Drug
Administration (FDA) approved linezolid on April 18, 2000.[120] Approval followed in Brazil (June
2000),[121] the United Kingdom (January 2001),[16][67] Japan and Canada (April 2001),[122][123][124] Europe
(throughout 2001),[125]and other countries in Latin America and Asia.[123]
As of 2009, linezolid is the only oxazolidinone antibiotic available.[126] Other members of this class
have entered development, such as posizolid (AZD2563),[127] ranbezolid (RBx
7644),[128] torezolid (TR-701),[126][129] and radezolid (RX-1741).[130]

Society and culture[edit]

Economics[edit]
Further information: Pharmacoeconomics and 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,[58] not to mention other costs (such as those associated with hospital stay).
With the medication becoming generic the price has decreased such that in United States the
wholesale cost of a course of treatment as of 2016 is about US$137.90.[12] In India as of 2015 a
month of linezolid, as would be used to treat tuberculosis cost about USS$60.[4]
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.[13] Reducing the length of hospital stay reduces the overall cost of treatment, even though
linezolid may have a higher acquisition costthat is, it may be more expensivethan comparable
antibiotics.
Studies have been conducted in several countries with different health care system models to
assess the 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.[13]
In 2009, Pfizer paid $2.3 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.[131] $1.3 billion was paid to settle criminal charges of illegally marketing the
anti-inflammatory valdecoxib, while $1 billion was paid in civil fines regarding illegal marketing of
three other drugs, including Zyvox.[132]
Brand names[edit]
Linezolid is marketed by Pfizer under the trade names Zyvox (in the United States, United Kingdom,
Australia, and several other countries), Zyvoxid (in Europe), and Zyvoxam (in Canada and Mexico).
Generics are also available, such as Lenzomore (in India, by Morepen), Linospan (in India,
by Cipla), Nezocin (in Pakistan, by Brookes), voxazoldin (in Egypt, by Rotabiogen), Lizomed (in
India, as a dry syrup by Aglowmed), and Linzolid (in Bangladesh, by Incepta).

References[edit]
1. ^ Jump up to:a b c d Marino PL, Sutin KM (2007). "Antimicrobial
therapy". The ICU book. Hagerstown, MD: Lippincott Williams &
Wilkins. p. 817. ISBN 0-7817-4802-X.
2. ^ Jump up to:a b c d e f g h "Linezolid". The American Society of Health-
System Pharmacists. Retrieved 8 December 2016.
3. ^ Jump up to:a b c d e f g h i j k Pfizer (2010-07-16). "Zyvox (linezolid)
Label Information" (PDF). Retrieved 2011-04-02.
4. ^ Jump up to:a b 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). (PDF). WHO. 2015. pp. 31
33. ISBN 978-92-4-069494-1. Retrieved 8 December 2016.
5. ^ Jump up to:a b "Linezolid Side Effects in Detail -
Drugs.com". www.drugs.com. Retrieved 11 December 2016.
6. ^ Jump up to:a b c Swaney SM, Aoki H, Ganoza MC, Shinabarger DL
(December 1, 1998). "The Oxazolidinone Linezolid Inhibits Initiation of
Protein Synthesis in Bacteria" (PDF). Antimicrobial Agents and
Chemotherapy. 42 (12): 32515. ISSN 0066-4804. PMC 106030
. PMID 9835522.
7. Jump up^ Mendes, RE; Deshpande, LM; Jones, RN (April 2014).
"Linezolid update: stable in vitro activity following more than a decade
of clinical use and summary of associated resistance
mechanisms.". Drug resistance updates : reviews and commentaries
in antimicrobial and anticancer chemotherapy. 17(12): 1
12. PMID 24880801. doi:10.1016/j.drup.2014.04.002. Emergence of
resistance has been limited ... It is still uncertain whether the
occurrences of such isolates are becoming more prevalent.
8. Jump up^ Li, Jie Jack; Corey, E. J. (2013). Drug Discovery: Practices,
Processes, and Perspectives. John Wiley & Sons. p. 6. ISBN 978-1-
118-35446-9.
9. Jump up^ Torok, Estee; Moran, Ed; Cooke, Fiona (2009). "Chapter 2
Antimicrobials". Oxford Handbook of Infectious Diseases and
Microbiology. OUP Oxford. ISBN 978-0-19-103962-1.
10. Jump up^ "WHO Model List of Essential Medicines (19th
List)" (PDF). World Health Organization. April 2015. Retrieved 8
December2016.
11. Jump up^ "Global Drug Facility Product Catalogue" (PDF). 2016.
Retrieved 4 January 2017.
12. ^ Jump up to:a b "NADAC as of 2016-12-07 |
Data.Medicaid.gov". Centers for Medicare and Medicaid Services.
Retrieved 11 December2016.
13. ^ Jump up to:a b c Grau S, Rubio-Terrs C (April 2008).
"Pharmacoeconomics of linezolid". Expert Opinion on
Pharmacotherapy. 9 (6): 9871000. ISSN 1465-
6566. PMID 18377341. doi:10.1517/14656566.9.6.987.
14. Jump up^ Wroe, David (2002-02-28). "An antibiotic to fight immune
bugs". The Age. Retrieved 2009-05-16.
15. Jump up^ Wilson AP, Cepeda JA, Hayman S, Whitehouse T, Singer
M, Bellingan G (August 2006). "In vitro susceptibility of Gram-positive
pathogens to linezolid and teicoplanin and effect on outcome in
critically ill patients" (PDF). Journal of Antimicrobial
Chemotherapy. 58 (2): 4703. ISSN 0305-
7453. PMID 16735420. doi:10.1093/jac/dkl233.
16. ^ Jump up to:a b [No authors listed] (2009-06-24). "Zyvox 600 mg Film-
Coated Tablets, 100 mg/5 ml Granules for Oral Suspension, 2 mg/ml
Solution for Infusion Summary of Product Characteristics (SPC)".
electronic Medicines Compendium. Retrieved 2009-07-03.
17. ^ Jump up to:a b c d e f g h i j k Herrmann DJ, Peppard WJ, Ledeboer NA,
Theesfeld ML, Weigelt JA, Buechel BJ (December 2008). "Linezolid
for the treatment of drug-resistant infections". Expert Review of Anti-
infective Therapy. 6 (6): 82548. ISSN 1478-
7210. PMID 19053895. doi:10.1586/14787210.6.6.825.
18. ^ Jump up to:a b c Falagas ME, Siempos II, Vardakas KZ (January
2008). "Linezolid versus glycopeptide or beta-lactam for treatment of
Gram-positive bacterial infections: meta-analysis of randomised
controlled trials". Lancet Infectious Diseases. 8 (1): 5366. ISSN 1473-
3099. PMID 18156089. doi:10.1016/S1473-3099(07)70312-
2. Structured abstract with quality assessment available at DARE.
19. Jump up^ Tascini C, Gemignani G, Doria R, et al. (June 2009).
"Linezolid treatment for gram-positive infections: a retrospective
comparison with teicoplanin". Journal of Chemotherapy. 21 (3): 311
6. ISSN 1120-009X. PMID 19567352. doi:10.1179/joc.2009.21.3.311.
20. Jump up^ Chow I, Lemos EV, Einarson TR (2008). "Management and
prevention of diabetic foot ulcers and infections: a health economic
review". PharmacoEconomics. 26 (12): 101935. ISSN 1170-
7690. PMID 19014203. doi:10.2165/0019053-200826120-00005.
21. Jump up^ Lipsky BA, Itani K, Norden C (January 2004). "Treating foot
infections in diabetic patients: a randomized, multicenter, open-label
trial of linezolid versus ampicillin-sulbactam/amoxicillin-
clavulanate". Clinical Infectious Diseases. 38 (1): 1724. ISSN 1058-
4838. PMID 14679443. doi:10.1086/380449.
22. ^ Jump up to:a b c d Pigrau, C; Almirante, B (April
2009). "Oxazolidinonas, glucopptidos y lipopptidos
cclicos" [Oxazolidinones, glycopeptides and cyclic
lipopeptides] (PDF). Enfermedades Infecciosas y Microbiologa
Clnica (in Spanish). 27 (4): 236
46. PMID 19406516. doi:10.1016/j.eimc.2009.02.004. Archived
from the original (PDF) on 2011-07-23.
23. Jump up^ Vardakas KZ, Horianopoulou M, Falagas ME (June 2008).
"Factors associated with treatment failure in patients with diabetic foot
 infections: An analysis of data from randomized controlled
trials". Diabetes Research and Clinical Practice. 80 (3): 344
51. ISSN 0168-
8227. PMID 18291550. doi:10.1016/j.diabres.2008.01.009.
24. Jump up^ Grammatikos A, Falagas ME (2008). "Linezolid for the
treatment of skin and soft tissue infection". Expert Review of
Dermatology. 3(5): 53948. doi:10.1586/17469872.3.5.539.
25. ^ Jump up to:a b Mandell LA, Wunderink RG, Anzueto A, et al. (March
2007). "Infectious Diseases Society of America/American Thoracic
Society consensus guidelines on the management of community-
acquired pneumonia in adults". Clinical Infectious Diseases. 44(Suppl
2): S2772. ISSN 1058-4838. PMID 17278083. doi:10.1086/511159.
26. Jump up^ BTS Pneumonia Guidelines Committee (2004-04-
30). "BTS guidelines for the management of community acquired
pneumonia in adults 2004 update" (PDF). British Thoracic Society.
Archived from the original (PDF) on 2009-04-07. Retrieved 2009-06-30.
27. ^ Jump up to:a b American Thoracic Society; Infectious Diseases
Society(February 2005). "Guidelines for the management of adults
with hospital-acquired, ventilator-associated, and healthcare-
associated pneumonia" (PDF). American Journal of Respiratory and
Critical Care Medicine. 171 (4): 388416. ISSN 1073-
449X. PMID 15699079. doi:10.1164/rccm.200405-644ST.
28. Jump up^ Koya D, Shibuya K, Kikkawa R, Haneda M (December
2004). "Successful recovery of infective endocarditis-induced rapidly
progressive glomerulonephritis by steroid therapy combined with
antibiotics: a case report" (PDF). BMC Nephrology. 5 (1):
18. PMC 544880 . PMID 15610562. doi:10.1186/1471-2369-5-18.
29. ^ Jump up to:a b c d e f g h Barbachyn MR, Ford CW (May 2003).
"Oxazolidinone structure-activity relationships leading to
linezolid". Angewandte Chemie International Edition in
English. 42 (18): 201023. ISSN 1433-
7851. PMID 12746812. doi:10.1002/anie.200200528.
30. Jump up^ Pankey GA, Sabath LD (March 2004). "Clinical relevance
of bacteriostatic versus bactericidal mechanisms of action in the
treatment of Gram-positive bacterial infections". Clinical Infectious
Diseases. 38 (6): 86470. ISSN 1058-
4838. PMID 14999632. doi:10.1086/381972.
31. Jump up^ Falagas ME, Manta KG, Ntziora F, Vardakas KZ (August
2006). "Linezolid for the treatment of patients with endocarditis: a
systematic review of the published evidence" (PDF). Journal of
Antimicrobial Chemotherapy. 58 (2): 27380. ISSN 0305-
7453. PMID 16735427. doi:10.1093/jac/dkl219.
32. Jump up^ Babcock HM, Ritchie DJ, Christiansen E, Starlin R, Little R,
Stanley S (May 2001). "Successful treatment of vancomycin-
resistant Enterococcus endocarditis with oral linezolid". Clinical
Infectious Diseases. 32 (9): 13735. ISSN 1058-
4838. PMID 11303275. doi:10.1086/319986.
33. Jump up^ Ang JY, Lua JL, Turner DR, Asmar BI (December 2003).
"Vancomycin-resistant Enterococcus faecium endocarditis in a
premature infant successfully treated with linezolid". The Pediatric
Infectious Disease Journal. 22 (12): 11013. ISSN 0891-
3668. PMID 14688576. doi:10.1097/01.inf.0000101784.83146.0c.
34. Jump up^ Archuleta S, Murphy B, Keller MJ (September 2004).
"Successful treatment of vancomycin-resistant Enterococcus
faecium endocarditis with linezolid in a renal transplant recipient with
human immunodeficiency virus infection". Transplant Infectious
 Disease. 6 (3): 1179. ISSN 1398-
2273. PMID 15569227. doi:10.1111/j.1399-3062.2004.00059.x.
35. Jump up^ Zimmer SM, Caliendo AM, Thigpen MC, Somani J (August
2003). "Failure of linezolid treatment for enterococcal
endocarditis". Clinical Infectious Diseases. 37 (3): e2930. ISSN 1058-
4838. PMID 12884185. doi:10.1086/375877.
36. Jump up^ Tsigrelis C, Singh KV, Coutinho TD, Murray BE, Baddour
LM (February 2007). "Vancomycin-Resistant Enterococcus faecalis
Endocarditis: Linezolid Failure and Strain Characterization of Virulence
Factors" (PDF). Journal of Clinical Microbiology. 45(2): 631
5. ISSN 0095-1137. PMC 1829077
. PMID 17182759. doi:10.1128/JCM.02188-06.
37. Jump up^ Berdal JE, Eskesen A (2008). "Short-term success, but
long-term treatment failure with linezolid for enterococcal
endocarditis". Scandinavian Journal of Infectious Diseases. 40 (9):
7656. ISSN 0036-
5548. PMID 18609208. doi:10.1080/00365540802087209.
38. Jump up^ Falagas ME, Siempos II, Papagelopoulos PJ, Vardakas KZ
(March 2007). "Linezolid for the treatment of adults with bone and joint
infections". International Journal of Antimicrobial Agents. 29(3): 233
9. ISSN 0924-
8579. PMID 17204407. doi:10.1016/j.ijantimicag.2006.08.030. Review.
39. Jump up^ Bassetti M, Vitale F, Melica G, et al. (March
2005). "Linezolid in the treatment of Gram-positive prosthetic joint
infections"(PDF). Journal of Antimicrobial Chemotherapy. 55 (3): 387
90. ISSN 0305-7453. PMID 15705640. doi:10.1093/jac/dki016.
40. Jump up^ Aneziokoro CO, Cannon JP, Pachucki CT, Lentino JR
(December 2005). "The effectiveness and safety of oral linezolid for
the primary and secondary treatment of osteomyelitis". Journal of
Chemotherapy. 17 (6): 64350. ISSN 1120-
009X. PMID 16433195. doi:10.1179/joc.2005.17.6.643.
41. Jump up^ Senneville E, Legout L, Valette M, et al. (August 2006).
"Effectiveness and tolerability of prolonged linezolid treatment for
chronic osteomyelitis: a retrospective study". Clinical
Therapeutics. 28 (8): 115563. ISSN 0149-
2918. PMID 16982292. doi:10.1016/j.clinthera.2006.08.001.
42. Jump up^ Rao N, Hamilton CW (October 2007). "Efficacy and safety
of linezolid for Gram-positive orthopedic infections: a prospective case
series". Diagnostic Microbiology and Infectious Disease. 59(2): 173
9. ISSN 0732-
8893. PMID 17574788. doi:10.1016/j.diagmicrobio.2007.04.006.
43. Jump up^ Papadopoulos A, Plachouras D, Giannitsioti E, Poulakou
G, Giamarellou H, Kanellakopoulou K (April 2009). "Efficacy and
tolerability of linezolid in chronic osteomyelitis and prosthetic joint
infections: a case-control study". Journal of Chemotherapy. 21 (2):
1659. ISSN 1120-
009X. PMID 19423469. doi:10.1179/joc.2009.21.2.165.
44. Jump up^ von der Lippe B, Sandven P, Brubakk O (February 2006).
"Efficacy and safety of linezolid in multidrug resistant tuberculosis
(MDR-TB)a report of ten cases". Journal of Infection. 52 (2): 92
6. ISSN 0163-4453. PMID 15907341. doi:10.1016/j.jinf.2005.04.007.
45. Jump up^ Park IN, Hong SB, Oh YM, et al. (September
2006). "Efficacy and tolerability of daily-half dose linezolid in patients
with intractable multidrug-resistant tuberculosis" (PDF). Journal of
Antimicrobial Chemotherapy. 58 (3): 7014. ISSN 0305-
7453. PMID 16857689. doi:10.1093/jac/dkl298.
46. Jump up^ Fortn J, Martn-Dvila P, Navas E, et al. (July
2005). "Linezolid for the treatment of multidrug-resistant
tuberculosis" (PDF). Journal of Antimicrobial Chemotherapy. 56 (1):
1805. ISSN 0305-7453. PMID 15911549. doi:10.1093/jac/dki148.
47. Jump up^ Jaksic B, Martinelli G, Perez-Oteyza J, Hartman CS,
Leonard LB, Tack KJ (March 2006). "Efficacy and safety of linezolid
compared with vancomycin in a randomized, double-blind study of
febrile neutropenic patients with cancer". Clinical Infectious
Diseases. 42 (5): 597607. ISSN 1058-
4838. PMID 16447103. doi:10.1086/500139. Criticism
in doi:10.1086/504431; author reply in doi:10.1086/504437.
48. ^ Jump up to:a b c d e f g h Moellering RC (January 2003). "Linezolid: the
first oxazolidinone antimicrobial" (PDF). Annals of Internal
Medicine. 138 (2): 13542. ISSN 0003-
4819. PMID 12529096. doi:10.7326/0003-4819-138-2-200301210-
00015.
49. Jump up^ Cottagnoud P, Gerber CM, Acosta F, Cottagnoud M, Neftel
K, Tuber MG (December 2000). "Linezolid against penicillin-sensitive
and -resistant pneumococci in the rabbit meningitis
model" (PDF). Journal of Antimicrobial Chemotherapy. 46 (6): 981
5. ISSN 0305-7453. PMID 11102418. doi:10.1093/jac/46.6.981.
50. ^ Jump up to:a b Sabbatani S, Manfredi R, Frank G, Chiodo F (June
2005). "Linezolid in the treatment of severe central nervous system
infections resistant to recommended antimicrobial compounds". Le
Infezioni in Medicina. 13 (2): 1129. ISSN 1124-
9390. PMID 16220032. Archived from the original on 2011-07-22.
51. Jump up^ Ntziora F, Falagas ME (February 2007). "Linezolid for the
treatment of patients with central nervous system infection". Annals of
Pharmacotherapy. 41 (2): 296308. ISSN 1060-
0280. PMID 17284501. doi:10.1345/aph.1H307. Structured abstract
with quality assessment available at DARE.
52. Jump up^ Tunkel AR, Hartman BJ, Kaplan SL, et al. (November
2004). "Practice guidelines for the management of bacterial
meningitis". Clinical Infectious Diseases. 39 (9): 126784. ISSN 1058-
4838. PMID 15494903. doi:10.1086/425368.
53. Jump up^ Naesens R, Ronsyn M, Druw P, Denis O, Ieven M,
Jeurissen A (June 2009). "Central nervous system invasion by
community-acquired methicillin-resistant Staphylococcus aureus: case
report and review of the literature". Journal of Medical
Microbiology. 58(Pt 9): 124751. ISSN 0022-
2615. PMID 19528145. doi:10.1099/jmm.0.011130-0.
54. ^ Jump up to:a b c [No authors listed] (March 16, 2007). "Information for
Healthcare Professionals: Linezolid (marketed as Zyvox)". U.S. Food
and Drug Administration (FDA). Retrieved 2010-09-15.
55. ^ Jump up to:a b Wilcox MH, Tack KJ, Bouza E, et al. (January 2009).
"Complicated skin and skin-structure infections and catheter-related
bloodstream infections: noninferiority of linezolid in a phase 3
study". Clinical Infectious Diseases. 48 (2): 20312. ISSN 1058-
4838. PMID 19072714. doi:10.1086/595686.
56. ^ Jump up to:a b c Ament PW, Jamshed N, Horne JP (February
2002). "Linezolid: its role in the treatment of gram-positive, drug-
resistant bacterial infections". American Family Physician. 65 (4): 663
70. ISSN 0002-838X. PMID 11871684.
57. Jump up^ Buck ML (June 2003). "Linezolid use for resistant Gram-
positive infections in children" (PDF). Pediatric Pharmacotherapy. 9 (6).
Retrieved 2009-06-08.
58. ^ Jump up to:a b c d e f g h Lexi-Comp (August 2008). "Linezolid". The
Merck Manual Professional. Retrieved on May 14, 2009.
59. Jump up^ Lovering AM, Le Floch R, Hovsepian L, et al. (March
2009). "Pharmacokinetic evaluation of linezolid in patients with major
thermal injuries". Journal of Antimicrobial Chemotherapy. 63 (3): 553
9. ISSN 0305-7453. PMID 19153078. doi:10.1093/jac/dkn541.
60. ^ Jump up to:a b Davaro RE, Glew RH, Daly JS
(2004). "Oxazolidinones, quinupristin-dalfopristin, and daptomycin". In
Gorbach SL, Bartlett JG, Blacklow NR. Infectious diseases.
Hagerstown, MD: Lippincott Williams & Wilkins. pp. 2413. ISBN 0-
7817-3371-5. Retrieved 2009-06-20.
61. Jump up^ Jones RN, Stilwell MG, Hogan PA, Sheehan DJ (April
2007). "Activity of Linezolid against 3,251 Strains of Uncommonly
Isolated Gram-Positive Organisms: Report from the SENTRY
Antimicrobial Surveillance Program". Antimicrobial Agents and
Chemotherapy. 51 (4): 14913. PMC 1855453
. PMID 17210770. doi:10.1128/AAC.01496-06.
62. Jump up^ Jodlowski TZ, Melnychuk I, Conry J (October 2007).
"Linezolid for the treatment of Nocardia spp. infections". Annals of
Pharmacotherapy. 41 (10): 16949. ISSN 1060-
0280. PMID 17785610. doi:10.1345/aph.1K196.
63. ^ Jump up to:a b c d [No authors listed] (2001). "Linezolid: First of a New
Drug Class for Gram-Positive Infections". Drugs & Therapy
Perspectives. 17 (9): 16. doi:10.2165/00042310-200117090-
00001. Free full text with registration at Medscape.
64. Jump up^ [No authors listed] (August 5, 2008). "Animal Bites
andPasteurella multocida: Information for Healthcare Staff". Health
Protection Agency. Archived from the original on January 26,
2010. Retrieved on 2009-05-15.
65. Jump up^ Geisler WM, Malhotra U, Stamm WE (December
2001). "Pneumonia and sepsis due to fluoroquinolone-
resistantCapnocytophaga gingivalis after autologous stem cell
transplantation" (PDF). Bone Marrow Transplantation. 28 (12): 1171
3. ISSN 0268-3369. PMID 11803363. doi:10.1038/sj.bmt.1703288.
66. ^ Jump up to:a b c Livermore DM (September
2000). "Quinupristin/dalfopristin and linezolid: where, when, which and
whether to use?" (PDF). Journal of Antimicrobial Chemotherapy. 46 (3):
34750. ISSN 0305-7453. PMID 10980159. doi:10.1093/jac/46.3.347.
67. ^ Jump up to:a b c d e f g h French G (May 2003). "Safety and tolerability
of linezolid" (PDF). Journal of Antimicrobial Chemotherapy. 51(Suppl
2): ii4553. ISSN 0305-
7453. PMID 12730142. doi:10.1093/jac/dkg253. Review. Includes
extensive discussion of the hematological adverse effects of linezolid.
68. ^ Jump up to:a b c d Metaxas EI, Falagas ME (July 2009). "Update on
the safety of linezolid". Expert Opinion on Drug Safety. 8 (4): 485
91. ISSN 1474-
0338. PMID 19538105. doi:10.1517/14740330903049706.
69. Jump up^ Zabel LT, Worm S (June 2005). "Linezolid contributed
to Clostridium difficile colitis with fatal outcome". Infection. 33 (3): 155
7. ISSN 0300-8126. PMID 15940418. doi:10.1007/s15010-005-4112-
6.
70. Jump up^ Pelez T, Alonso R, Prez C, Alcal L, Cuevas O, Bouza E
(May 2002). "In Vitro Activity of Linezolid against Clostridium
difficile" (PDF). Antimicrobial Agents and Chemotherapy. 46 (5): 1617
8. ISSN 0066-4804. PMC 127182
. PMID 11959617. doi:10.1128/AAC.46.5.1617-1618.2002.
71. Jump up^ Lin YH, Wu VC, Tsai IJ, et al. (October 2006). "High
frequency of linezolid-associated thrombocytopenia among patients
with renal insufficiency". International Journal of Antimicrobial
 Agents. 28 (4): 34551. ISSN 0924-
8579. PMID 16935472. doi:10.1016/j.ijantimicag.2006.04.017.
72. Jump up^ Spellberg B, Yoo T, Bayer AS (October 2004). "Reversal of
linezolid-associated cytopenias, but not peripheral neuropathy, by
administration of vitamin B6" (PDF). Journal of Antimicrobial
Chemotherapy. 54 (4): 8325. ISSN 0305-
7453. PMID 15317746. doi:10.1093/jac/dkh405.
73. Jump up^ Plachouras D, Giannitsioti E, Athanassia S, et al.
(November 2006). "No effect of pyridoxine on the incidence of
myelosuppression during prolonged linezolid treatment". Clinical
Infectious Diseases. 43 (9): e8991. ISSN 1058-
4838. PMID 17029128. doi:10.1086/508280.
74. ^ Jump up to:a b del Pino BM. Chemotherapy-induced Peripheral
Neuropathy. NCI Cancer Bulletin. Feb 23, 2010 [archived2011-12-
11];7(4):6.
75. Jump up^ Cooper, Raymond; Deakin, Jeffrey John (2016). "Africa's
gift to the world". Botanical Miracles: Chemistry of Plants That
Changed the World. CRC Press. pp. 4651. ISBN 9781498704304.
76. Jump up^ Keglevich, Pter; Hazai, Laszlo; Kalaus, Gyrgy; Szntay,
Csaba (2012). "Modifications on the basic skeletons of vinblastine and
vincristine". Molecules. 17: 5893
5914. PMID 22609781. doi:10.3390/molecules17055893.
77. Jump up^ Ravia, Enrique (2011). "Vinca alkaloids". The evolution of
drug discovery: From traditional medicines to modern drugs. John
Wiley & Sons. pp. 157159. ISBN 9783527326693.
78. Jump up^ Chemotherapy and polyneuropathies. European
Association of Neurooncology Magazine. 2012;12(1).
79. Jump up^ "Review: could Herceptin cause Peripheral sensory
neuropathy". Retrieved 4 May 2016.
80. Jump up^ Narita M, Tsuji BT, Yu VL (August 2007). "Linezolid-
associated peripheral and optic neuropathy, lactic acidosis, and
serotonin syndrome". Pharmacotherapy. 27 (8): 118997. ISSN 0277-
0008. PMID 17655517. doi:10.1592/phco.27.8.1189.
81. Jump up^ Bressler AM, Zimmer SM, Gilmore JL, Somani J (August
2004). "Peripheral neuropathy associated with prolonged use of
linezolid". Lancet Infectious Diseases. 4 (8): 52831. ISSN 1473-
3099. PMID 15288827. doi:10.1016/S1473-3099(04)01109-0.
82. Jump up^ Brown J, Aitken SL, van Mannen RP (June 2011).
"Potential for Linezolid-Related Blindness: a Review of Spontaneous
Adverse Event Reports". Pharmacotherapy. 31 (6): 585
90. PMID 21923442. doi:10.1592/phco.31.6.585.
83. Jump up^ Chao CC, Sun HY, Chang YC, Hsieh ST (January
2008). "Painful neuropathy with skin denervation after prolonged use
of linezolid". Journal of Neurology, Neurosurgery & Psychiatry. 79(1):
979. ISSN 0022-
3050. PMID 17766431. doi:10.1136/jnnp.2007.127910.
84. Jump up^ Saijo T, Hayashi K, Yamada H, Wakakura M (June 2005).
"Linezolid-induced optic neuropathy". American Journal of
Ophthalmology. 139 (6): 11146. ISSN 0002-
9394. PMID 15953450. doi:10.1016/j.ajo.2004.11.047.
85. ^ Jump up to:a b Barnhill AE, Brewer MT, Carlson SA (August
2012). "Adverse effects of antimicrobials via predictable or
idiosyncratic inhibition of host mitochondrial
components". Antimicrobial Agents and Chemotherapy. 56 (8): 4046
51. PMC 3421593 . PMID 22615289. doi:10.1128/AAC.00678-
12. Review. For the original case series, see Soriano A, Mir O,
Mensa J (November 2005). "Mitochondrial toxicity associated with
 linezolid". New England Journal of Medicine. 353 (21): 2305
6. ISSN 0028-
4793. PMID 16306535. doi:10.1056/NEJM200511243532123.
86. Jump up^ Javaheri M, Khurana RN, O'hearn TM, Lai MM, Sadun AA
(January 2007). "Linezolidinduced optic neuropathy: a mitochondrial
disorder?". British Journal of Ophthalmology. 91(1): 111
5. ISSN 0007-1161. PMC 1857552
. PMID 17179125. doi:10.1136/bjo.2006.102541.
87. Jump up^ McKee EE, Ferguson M, Bentley AT, Marks TA (June
2006). "Inhibition of Mammalian Mitochondrial Protein Synthesis by
Oxazolidinones" (PDF). Antimicrobial Agents and
Chemotherapy. 50 (6): 20429. ISSN 0066-4804. PMC 1479116
. PMID 16723564. doi:10.1128/AAC.01411-05.
88. Jump up^ Bishop E, Melvani S, Howden BP, Charles PG, Grayson
ML (April 2006). "Good Clinical Outcomes but High Rates of Adverse
Reactions during Linezolid Therapy for Serious Infections: a Proposed
Protocol for Monitoring Therapy in Complex
Patients" (PDF). Antimicrobial Agents and Chemotherapy. 50(4): 1599
602. ISSN 0066-4804. PMC 1426936
. PMID 16569895. doi:10.1128/AAC.50.4.1599-1602.2006.
89. Jump up^ Lawrence KR, Adra M, Gillman PK (June 2006). "Serotonin
toxicity associated with the use of linezolid: a review of postmarketing
data". Clinical Infectious Diseases. 42 (11): 157883. ISSN 1058-
4838. PMID 16652315. doi:10.1086/503839.
90. Jump up^ Huang V, Gortney JS (December 2006). "Risk of serotonin
syndrome with concomitant administration of linezolid and serotonin
agonists". Pharmacotherapy. 26 (12): 178493. ISSN 0277-
0008. PMID 17125439. doi:10.1592/phco.26.12.1784.
91. Jump up^ Waknine, Yael (September 5, 2008). "FDA Safety
Changes: Mirena, Zyvox, Orencia". Medscape. Retrieved 2008-09-
06.Freely available with registration.
92. Jump up^ Stalker DJ, Jungbluth GL (2003). "Clinical
pharmacokinetics of linezolid, a novel oxazolidinone
antibacterial". Clinical Pharmacokinetics. 42 (13): 1129
40. ISSN 0312-5963. PMID 14531724. doi:10.2165/00003088-
200342130-00004.
93. ^ Jump up to:a b Slatter JG, Stalker DJ, Feenstra KL, et al. (August 1,
2001). "Pharmacokinetics, metabolism, and excretion of linezolid
following an oral dose of [(14)C]linezolid to healthy human
subjects" (PDF). Drug Metabolism and Disposition. 29 (8): 1136
45. ISSN 0090-9556. PMID 11454733.
94. Jump up^ Sisson TL, Jungbluth GL, Hopkins NK (January 2002).
"Age and sex effects on the pharmacokinetics of linezolid". European
Journal of Clinical Pharmacology. 57 (11): 7937. ISSN 0031-
6970. PMID 11868801. doi:10.1007/s00228-001-0380-y.
95. Jump up^ Skripkin E, McConnell TS, DeVito J, et al. (October
2008). "R-01, a New Family of Oxazolidinones That Overcome
Ribosome-Based Linezolid Resistance" (PDF). Antimicrobial Agents
and Chemotherapy. 52 (10): 35507. ISSN 0066-4804. PMC 2565890
. PMID 18663023. doi:10.1128/AAC.01193-07.
96. Jump up^ Colca JR, McDonald WG, Waldon DJ, et al. (June
2003). "Cross-linking in the living cell locates the site of action of
oxazolidinone antibiotics" (PDF). Journal of Biological
Chemistry. 278 (24): 219729. ISSN 0021-
9258. PMID 12690106. doi:10.1074/jbc.M302109200.
97. Jump up^ Ippolito JA, Kanyo ZF, Wang D, et al. (June 2008). "Crystal
structure of the oxazolidinone antibiotic linezolid bound to the 50S
 ribosomal subunit". Journal of Medicinal Chemistry. 51 (12): 3353
6. ISSN 0022-2623. PMID 18494460. doi:10.1021/jm800379d.
98. Jump up^ Wilson DN, Schluenzen F, Harms JM, Starosta AL, Connell
SR, Fucini P (September 2008). "The oxazolidinone antibiotics perturb
the ribosomal peptidyl-transferase center and effect tRNA
positioning" (PDF). Proceedings of the National Academy of
Sciences. 105 (36): 1333944. ISSN 0027-8424. PMC 2533191
. PMID 18757750. doi:10.1073/pnas.0804276105.
99. ^ Jump up to:a b c d e f g Brickner SJ (1996). "Oxazolidinone antibacterial
agents". Current Pharmaceutical Design. 2 (2): 17594.Detailed
review of the discovery and development of the whole oxazolidinone
class, including information on synthesis and structure-activity
relationships.
100. Jump up^ European Medicines Agency (2011). "CHP Assessment
Report for Xarelto (EMA/CHMP/301607/2011)" (PDF). Retrieved 2012-
03-15.
101. ^ Jump up to:a b c Xu GY, Zhou Y, Xu MC (2006). "A convenient
synthesis of antibacterial linezolid from (S)-glyceraldehyde
acetonide"(PDF). Chinese Chemical Letters. 17 (3): 3024. Archived
from the original (PDF) on 2011-07-07.
102. ^ Jump up to:a b Kaiser CR, Cunico W, Pinheiro AC, de Oliveira AG,
Peralta MA, de Souza MV (2007). "Oxazolidinonas: uma nova classe
de compostos no combate tuberculose" [Oxazolidinones: a new
class of compounds against tuberculosis] (pdf). Revista Brasileira de
Farmcia (in Portuguese). 88 (2): 838.
103. Jump up^ US patent 5837870, Pearlman BA, Perrault WR,
Barbachyn MR, et al., "Process to prepare oxazolidinones", issued
1997-03-28 Retrieved on 2009-06-13.
104. Jump up^ Lohray BB, Baskaran S, Rao BS, Reddy BY, Rao IN
(June 1999). "A short synthesis of oxazolidinone derivatives linezolid
and eperezolid: A new class of antibacterials". Tetrahedron
Letters. 40 (26): 48556. doi:10.1016/S0040-4039(99)00893-X.
105. Jump up^ Perrault WR, Keeler JB, Snyder WC, et al. (June 25,
2008). "Convergent green synthesis of linezolid (Zyvox)", in 12th
Annual Green Chemistry and Engineering Conference, June 2426,
2008, New York, NY. Retrieved on 2009-06-08.
106. Jump up^ Tsiodras S, Gold HS, Sakoulas G, et al. (July 2001).
"Linezolid resistance in a clinical isolate of Staphylococcus
aureus". The Lancet. 358 (9277): 2078. ISSN 0140-
6736. PMID 11476839. doi:10.1016/S0140-6736(01)05410-1.
107. Jump up^ Jones RN, Ross JE, Castanheira M, Mendes RE
(December 2008). "United States resistance surveillance results for
linezolid (LEADER Program for 2007)". Diagnostic Microbiology and
Infectious Disease. 62 (4): 41626. ISSN 0732-
8893. PMID 19022153. doi:10.1016/j.diagmicrobio.2008.10.010.
108. Jump up^ Jones RN, Kohno S, Ono Y, Ross JE, Yanagihara K
(June 2009). "ZAAPS International Surveillance Program (2007) for
linezolid resistance: results from 5591 Gram-positive clinical isolates in
23 countries". Diagnostic Microbiology and Infectious Disease. 64 (2):
191201. ISSN 0732-
8893. PMID 19500528. doi:10.1016/j.diagmicrobio.2009.03.001.
109. Jump up^ Hope R, Livermore DM, Brick G, Lillie M, Reynolds R
(November 2008). "Non-susceptibility trends among staphylococci
from bacteraemias in the UK and Ireland, 200106" (PDF). Journal of
Antimicrobial Chemotherapy. 62 (Suppl 2): ii6574. ISSN 0305-
7453. PMID 18819981. doi:10.1093/jac/dkn353.
110. Jump up^ Auckland C, Teare L, Cooke F, et al. (November
2002). "Linezolid-resistant enterococci: report of the first isolates in the
United Kingdom" (PDF). Journal of Antimicrobial Chemotherapy. 50 (5):
7436. ISSN 0305-7453. PMID 12407134. doi:10.1093/jac/dkf246.
111. ^ Jump up to:a b Scheetz MH, Knechtel SA, Malczynski M,
Postelnick MJ, Qi C (June 2008). "Increasing Incidence of Linezolid-
Intermediate or -Resistant, Vancomycin-Resistant Enterococcus
faecium Strains Parallels Increasing Linezolid
Consumption" (PDF). Antimicrobial Agents and Chemotherapy. 52 (6):
22569. ISSN 0066-4804. PMC 2415807
. PMID 18391028. doi:10.1128/AAC.00070-08.
112. Jump up^ Schumacher A, Trittler R, Bohnert JA, Kmmerer K,
Pags JM, Kern WV (June 2007). "Intracellular accumulation of
linezolid inEscherichia coli, Citrobacter freundii and Enterobacter
aerogenes: role of enhanced efflux pump activity and
inactivation" (PDF). Journal of Antimicrobial Chemotherapy. 59 (6):
12614. ISSN 0305-7453. PMID 16971414. doi:10.1093/jac/dkl380.
113. Jump up^ Saager B, Rohde H, Timmerbeil BS, et al. (September
2008). "Molecular characterisation of linezolid resistance in two
vancomycin-resistant (VanB) Enterococcus faecium isolates using
Pyrosequencing". European Journal of Clinical Microbiology &
Infectious Diseases. 27 (9): 8738. ISSN 0934-
9723. PMID 18421487. doi:10.1007/s10096-008-0514-6.
114. Jump up^ Besier S, Ludwig A, Zander J, Brade V, Wichelhaus TA
(April 2008). "Linezolid Resistance in Staphylococcus aureus: Gene
Dosage Effect, Stability, Fitness Costs, and Cross-
Resistances" (PDF). Antimicrobial Agents and Chemotherapy. 52 (4):
15702. ISSN 0066-4804. PMC 2292563
. PMID 18212098. doi:10.1128/AAC.01098-07.
115. Jump up^ Feng J, Lupien A, Gingras H, et al. (May
2009). "Genome sequencing of linezolid-resistant Streptococcus
pneumoniae mutants reveals novel mechanisms of
resistance". Genome Research. 19 (7): 121423. ISSN 1088-
9051. PMC 2704432 . PMID 19351617. doi:10.1101/gr.089342.108.
116. Jump up^ Lincopan N, de Almeida LM, Elmor de Arajo MR,
Mamizuka EM (April 2009). "Linezolid resistance in Staphylococcus
epidermidis associated with a G2603T mutation in the 23S rRNA
gene". International Journal of Antimicrobial Agents. 34 (3): 281
2. ISSN 0924-
8579. PMID 19376688. doi:10.1016/j.ijantimicag.2009.02.023.
117. Jump up^ Liakopoulos A, Neocleous C, Klapsa D, et al. (July
2009). "A T2504A mutation in the 23S rRNA gene responsible for
high-level resistance to linezolid of Staphylococcus
epidermidis". Journal of Antimicrobial Chemotherapy. 64 (1): 206
7. ISSN 0305-7453. PMID 19429927. doi:10.1093/jac/dkp167.
118. Jump up^ Slee AM, Wuonola MA, McRipley RJ, et al. (November
1987). "Oxazolidinones, a new class of synthetic antibacterial agents:
in vitro and in vivo activities of DuP 105 and DuP
721" (PDF). Antimicrobial Agents and Chemotherapy. 31 (11): 1791
7. ISSN 0066-4804. PMC 175041
. PMID 3435127. doi:10.1128/AAC.31.11.1791.
119. Jump up^ Ford CW, Zurenko GE, Barbachyn MR (August 2001).
"The discovery of linezolid, the first oxazolidinone antibacterial
agent". Current Drug Targets Infectious Disorders. 1 (2): 181
99. ISSN 1568-
0053. PMID 12455414. doi:10.2174/1568005014606099.
120. Jump up^ "Drug Approval Package: Zyvox". FDA Center for Drug
Evaluation and Research. November 20, 2001. Archived from the
original on 2008-01-10. Retrieved 2009-01-17. 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.
121. Jump up^ ANVISA (June 5, 2000). "Resoluo n 474, de 5 de
junho de 2000" [Resolution number 474, of June 5, 2000] (in
Portuguese). National Health Surveillance Agency. Archived from the
original on July 19, 2011. Retrieved 2009-05-19.
122. Jump up^ Irinoda K, Nomura S, Hashimoto M (October 2002).
"[Antimicrobial and clinical effect of linezolid (Zyvox), new class of
synthetic antibacterial drug]". Nippon Yakurigaku Zasshi (in
Japanese). 120 (4): 24552. ISSN 0015-
5691. PMID 12425150. doi:10.1254/fpj.120.245.
123. ^ Jump up to:a b "Canada Approves Marketing Of Zyvoxam
(Linezolid) For Gram Positive Infections" (Press release). May 8, 2001.
Retrieved 2009-05-18.
124. Jump up^ Karlowsky JA, Kelly LJ, Critchley IA, Jones ME,
Thornsberry C, Sahm DF (June 2002). "Determining Linezolid's
Baseline In Vitro Activity in Canada Using Gram-Positive Clinical
Isolates Collected prior to Its National Release" (PDF). Antimicrobial
Agents and Chemotherapy. 46 (6): 198992. ISSN 0066-
4804. PMC 127260 . PMID 12019122. doi:10.1128/AAC.46.6.1989-
1992.2002.
125. Jump up^ "Pharmacia Corporation Reports 17% Increase In
Second-Quarter Earnings-Per-Share Driven By 61% Increase In
Pharmaceutical Earnings" (Press release). Pharmacia Corporation.
July 25, 2001. Archived from the original on May 9, 2012.
Retrieved 2009-05-19.
126. ^ Jump up to:a b Livermore DM, Mushtaq S, Warner M, Woodford N
(April 2009). "Activity of oxazolidinone TR-700 against linezolid-
susceptible and -resistant staphylococci and enterococci". Journal of
Antimicrobial Chemotherapy. 63 (4): 7135. ISSN 0305-
7453. PMID 19164418. doi:10.1093/jac/dkp002.
127. Jump up^ Howe RA, Wootton M, Noel AR, Bowker KE, Walsh TR,
MacGowan AP (November 2003). "Activity of AZD2563, a Novel
Oxazolidinone, against Staphylococcus aureus Strains with Reduced
Susceptibility to Vancomycin or Linezolid" (PDF). Antimicrobial Agents
and Chemotherapy. 47 (11): 36512. ISSN 0066-4804. PMC 253812
. PMID 14576139. doi:10.1128/AAC.47.11.3651-3652.2003.
128. Jump up^ Kalia V, Miglani R, Purnapatre KP, et al. (April
2009). "Mode of Action of Ranbezolid against Staphylococci and
Structural Modeling Studies of Its Interaction with
Ribosomes". Antimicrobial Agents and Chemotherapy. 53 (4): 1427
33. ISSN 0066-4804. PMC 2663096
. PMID 19075051. doi:10.1128/AAC.00887-08.
129. Jump up^ "Trius Completes Enrollment In Phase 2 Clinical Trial
Evaluating Torezolid (TR-701) In Patients With Complicated Skin And
Skin Structure Infections" (Press release). 2009-01-27.
Retrieved 2009-05-17.
130. Jump up^ "Rx 1741". Rib-X Pharmaceuticals. 2009. Archived
from the original on 2009-02-26. Retrieved 2009-05-17.
131. Jump up^ "Pfizer agrees record fraud fine". BBC News. September
2, 2009. Retrieved 2009-09-12.
 132. Jump up^ Harris, Gardiner (September 2, 2009). "Pfizer pays $2.3
billion to settle marketing case". The New York Times. Retrieved 2009-
09-12.

[show]

Antibacterials: protein synthesis inhibitors (J01A, J01B, J01F, J01G, QJ01XQ)

[show]

Monoamine metabolism modulators

Categories:
2000 introductions
Monoamine oxidase inhibitors
Morpholines
Fluoroarenes
Oxazolidinone antibiotics
Pfizer products
World Health Organization essential medicines
Anti-tuberculosis drugs
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