Introduction
Linezolid is the first member of the oxazolidinone class of antibiotics, representing a significant advancement in antimicrobial therapy. Approved by the FDA in 2000, it offers a unique mechanism of action against resistant Gram-positive pathogens. This synthetic antibacterial agent has become particularly valuable in treating infections caused by multidrug-resistant organisms including methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus (VRE).
Mechanism of Action
Linezolid exerts its antibacterial effect by inhibiting bacterial protein synthesis through binding to the 50S ribosomal subunit. Specifically, it binds to the 23S ribosomal RNA of the 50S subunit, preventing formation of the 70S initiation complex. This mechanism is distinct from other protein synthesis inhibitors like macrolides, lincosamides, and aminoglycosides, resulting in no cross-resistance with these classes. Linezolid is bacteriostatic against enterococci and staphylococci and bactericidal against most streptococci.
Indications
Linezolid is FDA-approved for:
- Complicated skin and skin structure infections caused by susceptible Gram-positive bacteria
- Nosocomial pneumonia caused by Staphylococcus aureus (methicillin-susceptible and resistant strains) or Streptococcus pneumoniae
- Community-acquired pneumonia caused by susceptible Gram-positive organisms
- Vancomycin-resistant Enterococcus faecium infections
- Uncomplicated skin and skin structure infections
Off-label uses include:
- Treatment of multidrug-resistant tuberculosis (as part of combination therapy)
- Bone and joint infections caused by resistant Gram-positive organisms
- Central nervous system infections caused by susceptible organisms
Dosage and Administration
Adults:- 600 mg IV or orally every 12 hours
- Duration: 10-14 days for most indications, up to 28 days for specific infections
- Neonates (<7 days): 10 mg/kg every 12 hours
- Neonates (≥7 days): 10 mg/kg every 8 hours
- Children and adolescents: 10 mg/kg every 8 hours (maximum 600 mg/dose)
- Renal impairment: No dosage adjustment required
- Hepatic impairment: No dosage adjustment required
- Elderly: No dosage adjustment required
- Oral formulation may be taken with or without food
- IV formulation should be administered over 30-120 minutes
Pharmacokinetics
Absorption: Oral bioavailability approximately 100% (not affected by food) Distribution: Widely distributed to well-perfused tissues; volume of distribution ~40-50 L Protein binding: Approximately 31% (primarily to albumin) Metabolism: Primarily by hepatic oxidation (non-enzymatic) Elimination: Half-life ~4-5 hours; primarily non-renal clearance (65%); 30% excreted unchanged in urine Special considerations: Good penetration into bone, CSF, and epithelial lining fluidContraindications
- Known hypersensitivity to linezolid or any component of the formulation
- Patients taking monoamine oxidase inhibitors (MAOIs) or within 2 weeks of MAOI therapy
- Patients with uncontrolled hypertension, pheochromocytoma, thyrotoxicosis, carcinoid syndrome, or bipolar disorder
- Patients with a history of serotonin syndrome or neuroleptic malignant syndrome
Warnings and Precautions
Myelosuppression: Thrombocytopenia, anemia, leukopenia, and pancytopenia have been reported. Monitor CBC weekly, especially in patients receiving therapy longer than 2 weeks. Serotonin syndrome: May occur when used with serotonergic drugs. Monitor for mental status changes, autonomic instability, neuromuscular symptoms. Peripheral and optic neuropathy: Reported primarily with prolonged use (>28 days). Monitor visual function in patients receiving extended therapy. Lactic acidosis: Reversible, potentially fatal cases reported. Monitor for recurrent nausea/vomiting, unexplained acidosis. Hypoglycemia: Enhanced insulin secretion may occur, particularly with oral hypoglycemic agents. Clostridioides difficile-associated diarrhea: Reported with nearly all antibacterial agents.Drug Interactions
Significant interactions:- Serotonergic agents (SSRIs, SNRIs, TCAs, triptans): Increased risk of serotonin syndrome
- Adrenergic agents (pseudoephedrine, phenylpropanolamine): Potentiated pressor response
- Tyramine-containing foods: Potential hypertensive crisis (weak MAOI activity)
- Rifampin: Decreased linezolid concentrations
Adverse Effects
Common (≥1%):- Diarrhea (3-11%)
- Headache (0.5-11%)
- Nausea (3-10%)
- Vomiting (1-4%)
- Thrombocytopenia (2-4%)
- Myelosuppression (thrombocytopenia, anemia, leukopenia)
- Peripheral neuropathy
- Optic neuropathy
- Serotonin syndrome
- Lactic acidosis
- Clostridioides difficile-associated diarrhea
- Hypoglycemia
Monitoring Parameters
- Complete blood count (weekly, especially beyond 2 weeks of therapy)
- Signs/symptoms of serotonin syndrome (mental status changes, autonomic instability, neuromuscular symptoms)
- Visual function (for courses >28 days)
- Signs of peripheral neuropathy
- Serum lactate levels if symptoms suggest lactic acidosis
- Blood glucose in diabetic patients
- Signs of superinfection or C. difficile infection
Patient Education
- Complete the full course of therapy even if feeling better
- Oral formulation may be taken with or without food
- Report any symptoms of serotonin syndrome: agitation, hallucinations, fever, sweating, shivering, fast heart rate, muscle stiffness, twitching, nausea, vomiting, diarrhea
- Report visual changes or numbness/tingling in extremities
- Avoid large quantities of tyramine-rich foods (aged cheeses, fermented meats, draft beers, soy products)
- Inform all healthcare providers about linezolid use due to interaction potential
- Diabetic patients should monitor blood glucose closely as hypoglycemia may occur
- Report watery or bloody diarrhea during or after treatment
References
1. Stevens DL, et al. Linezolid versus vancomycin for the treatment of methicillin-resistant Staphylococcus aureus infections. Clin Infect Dis. 2002;34(11):1481-1490. 2. FDA Prescribing Information: Zyvox (linezolid). Pfizer Laboratories; 2021. 3. Livermore DM. Linezolid in vitro: mechanism and antibacterial spectrum. J Antimicrob Chemother. 2003;51 Suppl 2:ii9-ii16. 4. Welshman IR, et al. Linezolid: pharmacokinetics and tissue penetration. J Antimicrob Chemother. 2001;48(6):881-884. 5. Bernstein WB, et al. Linezolid-associated neurotoxicity. Clin Infect Dis. 2002;35(7):874-877. 6. Spellberg B, et al. Safety and efficacy of linezolid for treatment of extensively drug-resistant tuberculosis. Antimicrob Agents Chemother. 2012;56(6):3273-3276. 7. Gerson SL, et al. Hematologic effects of linezolid: summary of clinical experience. Antimicrob Agents Chemother. 2002;46(8):2725-2726. 8. Lawrence KR, et al. Serotonin toxicity associated with the use of linezolid: a review of postmarketing data. Clin Infect Dis. 2006;42(11):1578-1583.