Introduction
Zyvox (linezolid) is a synthetic antibacterial agent belonging to the oxazolidinone class, developed for the treatment of serious infections caused by multidrug-resistant Gram-positive pathogens. It represents a crucial therapeutic option in the era of antimicrobial resistance, particularly against vancomycin-resistant Enterococcus faecium (VRE) and methicillin-resistant Staphylococcus aureus (MRSA).
Mechanism of Action
Linezolid exerts its antibacterial effects by binding to the 50S ribosomal subunit, thereby inhibiting the formation of the initiation complex for protein synthesis. This mechanism is distinct from other protein synthesis inhibitors, as it prevents the assembly of the functional 70S ribosomal complex rather than targeting elongation factors. This unique mechanism contributes to its activity against resistant organisms and the lack of cross-resistance with other antimicrobial classes.
Indications
FDA-approved indications include:
- Complicated skin and skin structure infections (including diabetic foot infections without osteomyelitis)
- Community-acquired pneumonia
- Hospital-acquired pneumonia
- Vancomycin-resistant Enterococcus faecium infections
- Uncomplicated skin and skin structure infections
Off-label uses may include:
- Bone and joint infections
- Central nervous system infections
- Endocarditis caused by resistant Gram-positive organisms
Dosage and Administration
Standard dosing:
- Adults: 600 mg IV or orally every 12 hours
- Pediatric patients (>12 years): 600 mg every 12 hours
- Pediatric patients (<12 years): 10 mg/kg every 8 hours
Duration of therapy: Typically 10-14 days, depending on infection type and clinical response Special populations:
- Renal impairment: No dosage adjustment required
- Hepatic impairment: Use with caution; no specific dosage recommendations
- Elderly: No dosage adjustment required
- Pregnancy: Category C - use only if potential benefit justifies potential risk
Pharmacokinetics
Absorption: Oral bioavailability approximately 100% (may be taken without regard to meals)
Distribution: Volume of distribution 40-50 L; good tissue penetration including bone, lung, and CNS
Metabolism: Primarily via hepatic oxidation (non-CYP450 mediated)
Elimination: Half-life 4-5 hours; primarily renal elimination (30% unchanged drug, 50% as metabolites)
Protein binding: Approximately 31%
Contraindications
- Known hypersensitivity to linezolid or any component of the formulation
- Concomitant use with serotonergic drugs (unless closely monitored)
- Uncontrolled hypertension
- Pheochromocytoma
- Carcinoid syndrome
- Untreated hyperthyroidism
Warnings and Precautions
Myelosuppression: Thrombocytopenia, anemia, leukopenia, and pancytopenia have been reported. Monitor CBC weekly, especially with prolonged therapy (>2 weeks). Serotonin syndrome: Risk when used with serotonergic agents. Monitor for mental status changes, autonomic instability, neuromuscular symptoms. Peripheral and optic neuropathy: Reported with prolonged use (>28 days). Monitor visual function and neurological symptoms. Lactic acidosis: Rare but serious complication. Monitor for recurrent nausea/vomiting, unexplained acidosis. Monoamine oxidase inhibition: Linezolid is a weak, reversible MAO inhibitor. Avoid tyramine-rich foods and sympathomimetic agents.
Drug Interactions
Significant interactions:
- Serotonergic agents (SSRIs, SNRIs, TCAs, tramadol, meperidine): Increased risk of serotonin syndrome
- Adrenergic agents (pseudoephedrine, phenylpropanolamine): Potential hypertensive crisis
- Tyramine-rich foods: Potential hypertensive reaction
- Rifampin: May decrease linezolid concentrations
Adverse Effects
Common (>10%):
- Diarrhea (3-11%)
- Headache (4-11%)
- Nausea (3-10%)
Less common (1-10%):
- Vomiting
- Constipation
- Rash
- Insomnia
- Dizziness
Serious (<1%):
- Thrombocytopenia
- Anemia
- Peripheral neuropathy
- Optic neuropathy
- Lactic acidosis
- Serotonin syndrome
- Clostridium difficile-associated diarrhea
Monitoring Parameters
- Complete blood count (weekly during therapy)
- Neurological examination (vision, peripheral sensation)
- Signs/symptoms of serotonin syndrome
- Blood pressure monitoring
- Serum lactate levels if symptomatic
- Clinical response to therapy
- Renal and hepatic function (baseline and periodically)
Patient Education
- Complete the full course of therapy as prescribed
- Take oral formulation without regard to meals
- Report any visual changes, numbness, or tingling immediately
- Avoid tyramine-rich foods (aged cheeses, fermented meats, draft beers)
- Inform all healthcare providers about linezolid use
- Report any signs of bleeding or unusual bruising
- Notify provider if taking antidepressants or migraine medications
- Seek immediate medical attention for severe headache, palpitations, or confusion
References
1. FDA Prescribing Information: Zyvox (linezolid) [2023]
2. Stevens DL, et al. Practice Guidelines for the Diagnosis and Management of Skin and Soft Tissue Infections. Clin Infect Dis. 2014;59(2):e10-e52
3. Liu C, et al. Clinical Practice Guidelines by the Infectious Diseases Society of America for the Treatment of Methicillin-Resistant Staphylococcus Aureus Infections in Adults and Children. Clin Infect Dis. 2011;52(3):e18-e55
4. Welshman IR, et al. Linezolid: pharmacokinetics and tissue penetration. J Antimicrob Chemother. 2001;48 Suppl 1:39-44
5. Bishop E, et al. Linezolid-induced serotonin toxicity: a systematic review. Expert Opin Drug Saf. 2015;14(11):1765-77
6. Spellberg B, et al. Novel approaches are needed to develop tomorrow's antibacterial therapies. Am J Respir Crit Care Med. 2015;191(2):135-40
Note: This information is intended for educational purposes only and should not replace clinical judgment. Always consult current prescribing information and clinical guidelines.
