Linezolid !
An oral or IV oxazolidinone for MRSA, VRE and drug-resistant TB; watch platelets, nerves and serotonin-drug interactions.
Updated 2026-11-01
The figure shows linezolid in the large (50S) ribosomal subunit of Staphylococcus aureus, a real clinical target. A structure of the human mitochondrial ribosome with linezolid also exists (PDB 9CN3) and helps explain its mitochondrial toxicity.
Mechanism of action
Linezolid binds the 23S rRNA of the 50S subunit and stops formation of the 70S initiation complex, so translation never starts. It is bacteriostatic against staphylococci and enterococci and bactericidal for most streptococci. Resistance comes from point mutations in 23S rRNA. Mitochondrial ribosomes resemble bacterial ones, which is the likely basis of its blood, nerve and lactate toxicity.
- Binds the 23S rRNA of the 50S subunit
- The 70S initiation complex cannot form
- Protein synthesis never starts
- Growth stops (staphylococci, enterococci)
Pharmacokinetics
- Absorption
- Absorbed almost completely by mouth (bioavailability about 100%), so oral and IV doses are the same.
- Distribution
- Spreads well to well-perfused tissues; about 31% bound to plasma proteins.
- Metabolism
- Oxidation of its morpholine ring to two inactive metabolites, without the cytochrome P450 system.
- Elimination
- Mostly in the urine, as unchanged drug and its two metabolites; almost none in the faeces.
Indications
- Hospital-acquired pneumonia by Staphylococcus aureus (including MRSA) or Streptococcus pneumoniae. Hospital-acquired and ventilator-associated pneumonia →
- Community-acquired pneumonia by pneumococcus or S. aureus. Community-acquired pneumonia →
- Complicated skin infections, including diabetic foot infection without osteomyelitis. Diabetic foot →
- Vancomycin-resistant Enterococcus faecium infections, including bacteremia. MRSA and other multidrug-resistant organism infections →
- Part of combination regimens for extensively drug-resistant tuberculosis. Tuberculosis →
Adverse effects
Common
- Diarrhoea, nausea, headache
- Taste change, tongue and superficial tooth discoloration
- Vaginal yeast infection
Contraindications
- Hypersensitivity to linezolid
- Current use of an MAO inhibitor, or use within the previous two weeks
- Without blood-pressure monitoring: uncontrolled hypertension, pheochromocytoma, thyrotoxicosis or sympathomimetic drugs
Key interactions
- SSRIs, SNRIs, tricyclics, triptans, buspirone, opioids such as pethidine
- Serotonin syndrome (agitation, fever, sweating, clonus, rigidity); avoided or closely monitored.
- Pseudoephedrine, phenylpropanolamine, vasopressors, dopaminergic drugs
- Exaggerated rise in blood pressure; starting doses of adrenergic agents are reduced and titrated.
- Tyramine-rich food (aged cheese, cured or fermented meat, sauerkraut, soy sauce, tap beer, red wine)
- Pressor reaction with large amounts.
- Insulin and oral glucose-lowering drugs
- Symptomatic hypoglycaemia.
- Rifampicin
- Lowers linezolid exposure.
What is monitored
- Complete blood count weekly, especially beyond two weeks or with prior cytopenias or kidney or liver disease
- Vision (acuity and colour) and nerve symptoms in long courses
- Signs of serotonin syndrome when combined with serotonergic drugs
- Blood glucose in diabetics; lactate if there is unexplained nausea, vomiting or acidosis
Administration and safety
- Oral tablets, suspension or ready-to-use IV infusion; the IV and oral routes are interchangeable.
- Tablets and suspension can be given with or without food.
- Before starting, the medication list is reviewed for MAO inhibitors and serotonergic or adrenergic drugs.
Nursing care
- Baseline blood count, blood pressure and medication review (antidepressants, decongestants, MAO inhibitors).
- Watch for bleeding, bruising or infection that may point to low blood counts.
- Watch for agitation, fever, tremor or clonus in patients on serotonergic drugs.
- Teaching: avoid large amounts of tyramine-rich foods; report vision change, numbness, tingling, rapid breathing or diarrhoea.
Pregnancy and breastfeeding
Published and post-marketing case reports have not identified a drug-related risk of birth defects or miscarriage; it is used in pregnancy when the benefit justifies it.
Test yourself
Think of the answer, then tap the question to see it.
A patient on sertraline starts linezolid and becomes agitated, febrile and tremulous with clonus. What is the likely diagnosis?
Serotonin syndrome: linezolid weakly inhibits MAO and adds to the serotonergic effect of the SSRI.
Which blood test is checked weekly during linezolid treatment, and why?
The complete blood count, because linezolid causes myelosuppression, especially thrombocytopenia, that grows with treatment length.
Why can linezolid be switched from IV to tablets without changing the dose?
Its oral bioavailability is about 100%, so both routes give the same exposure.
Why does linezolid not treat a gram-negative bloodstream infection?
It has no clinical activity against gram-negative pathogens; specific gram-negative therapy is needed.
Related drugs
Related conditions
- Hospital-acquired and ventilator-associated pneumonia
- Community-acquired pneumonia
- Diabetic foot
- MRSA and other multidrug-resistant organism infections
- Tuberculosis
← Back to the class: Oxazolidinones
Educational content on how drugs work; not a prescribing guide and no substitute for a health professional's advice. No doses are given.
Sources: DailyMed - LINEZOLID tablet, film coated (DailyMed (U.S. National Library of Medicine), 2026); Linezolid: MedlinePlus Drug Information (MedlinePlus (U.S. National Library of Medicine), 2026); Goodman & Gilman's The Pharmacological Basis of Therapeutics, 14th ed., ch. 60 (McGraw Hill, 2023); RCSB PDB - 4WFA: The crystal structure of the large ribosomal subunit of Staphylococcus aureus in complex with linezolid (RCSB Protein Data Bank, 2026).
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Representative model, for educational purposes only.