linezolid
Brand: Zyvox
Prototype Drug
Drug Class: oxazolidinone antibiotic
Drug Family: antibiotic
Subclass: first oxazolidinone
Organ Systems: infectious-disease
Mechanism of Action
Binds to a unique site on the 50S ribosomal subunit, preventing formation of the 70S initiation complex and blocking protein synthesis initiation; bacteriostatic against most organisms but bactericidal against streptococci. Active against MRSA, VRE, and drug-resistant gram-positives.
50S ribosomal subunit (23S rRNA) — unique binding site
Indications
- MRSA infections (including pneumonia)
- VRE infections
- complicated skin/soft tissue infections due to gram-positive organisms
- nosocomial pneumonia due to S. aureus (MRSA/MSSA)
Contraindications
- concurrent or recent (within 2 weeks) MAOI use (serotonin syndrome)
- uncontrolled hypertension, pheochromocytoma (MAO-A inhibition)
- linezolid hypersensitivity
Adverse Effects
Common
- nausea
- diarrhea
- headache
- thrombocytopenia (duration-dependent)
Serious
- myelosuppression (thrombocytopenia, anemia — primarily with >2 weeks use)
- serotonin syndrome (when combined with serotonergic drugs)
- peripheral neuropathy (prolonged use)
- optic neuropathy (vision changes — stop drug)
- lactic acidosis
Pharmacokinetics (ADME)
| Absorption | 100% oral bioavailability; IV and oral doses are completely interchangeable |
| Distribution | widely distributed; good lung tissue penetration (ELF concentrations >MIC for S. aureus) |
| Metabolism | non-enzymatic oxidation to two inactive metabolites; NOT a CYP substrate but IS a weak MAO-A inhibitor |
| Excretion | renal (50% as metabolites, 30% unchanged) and fecal |
| Half-life | 4.5–5.5 hours |
| Onset | rapid |
| Peak | 1–2 hours (oral) |
| Duration | 12 hours |
| Protein Binding | 31% |
| Vd | moderate |
Drug Interactions
| Drug / Agent | Mechanism | Severity |
|---|---|---|
| SSRIs/SNRIs/TCAs/MAOIs/triptans | linezolid is a weak MAO-A inhibitor; combination can cause serotonin syndrome | major |
| dopaminergic/adrenergic agents (epinephrine, dopamine, norepinephrine) | MAO-A inhibition potentiates catecholamine response; hypertensive crisis risk | major |
| tyramine-containing foods | MAO-A inhibition impairs tyramine metabolism; hypertensive crisis | major |
Nursing Considerations
- Screen for all serotonergic drugs (SSRIs, SNRIs, TCAs, triptans, tramadol, fentanyl) before initiating linezolid; contact the prescriber if any are present — serotonin syndrome can be life-threatening.
- Monitor CBC twice weekly during therapy; thrombocytopenia is the most common serious adverse effect and is duration-dependent (typically after 2 weeks).
- Provide a low-tyramine diet list and counsel patients to avoid aged cheeses, cured meats, fermented products during linezolid therapy.
- Monitor for visual changes; optic neuropathy manifesting as blurred or color vision changes requires immediate discontinuation and ophthalmology referral.
Clinical Pearls
- Linezolid is the only class of antibiotic that targets the 50S subunit at the initiation complex rather than the elongation step, explaining its lack of cross-resistance with other protein synthesis inhibitors.
- Linezolid achieves lung epithelial lining fluid concentrations exceeding plasma levels, making it an effective alternative to vancomycin for MRSA pneumonia, particularly when vancomycin's limited tissue penetration is a concern.
Safety Profile
Pregnancy use-with-caution
Lactation use-with-caution
Renal Adjustment Not required
Hepatic Adjustment Not required
TDM Not required
Concordance Terms
Cross-referenced clinical concepts — click any term to see all content where it appears.