What is the recommended adult dosing regimen for linezolid, including dose, route, treatment duration, renal or hepatic adjustments, and monitoring for drug interactions?

Linezolid Adult Dosing

The standard adult dose of linezolid is 600 mg every 12 hours, administered either intravenously or orally, for all serious Gram-positive infections including pneumonia, complicated skin and soft tissue infections, bacteremia, and bone/joint infections. 1, 2

Standard Dosing Regimen

• Administer 600 mg IV or PO every 12 hours for complicated skin and soft tissue infections, nosocomial pneumonia, community-acquired pneumonia, bacteremia, osteomyelitis, septic arthritis, CNS infections, and vancomycin-resistant Enterococcus faecium infections 1, 2
• The oral and IV formulations are fully bioavailable and interchangeable without dose adjustment, allowing seamless transition between routes 3, 4
• For uncomplicated skin and soft tissue infections only, a lower dose of 400 mg every 12 hours may be used 5

Renal and Hepatic Dosing

• No dose adjustment is required for any degree of renal impairment, including severe renal insufficiency or patients on hemodialysis 3, 5
• No dose adjustment is required for mild to moderate hepatic impairment 4, 5
• Use caution in severe renal insufficiency requiring hemodialysis, as metabolite accumulation occurs (7-8 fold higher exposure), though the parent drug dosing remains unchanged 4

Duration of Therapy by Indication

• Complicated skin and soft tissue infections: 7-14 days 1
• Pneumonia (community-acquired or nosocomial): 7-21 days 6, 1
• Uncomplicated bacteremia: 7-14 days 6
• Complicated bacteremia: 4-6 weeks 6
• Osteomyelitis: Minimum 6-8 weeks, with consideration for additional 1-3 months of oral therapy 2
• Septic arthritis: 3-4 weeks 2
• CNS infections (meningitis, brain abscess): 2-6 weeks depending on specific infection 1, 2
• Infective endocarditis: Minimum 6 weeks 1

Critical Monitoring Requirements

• Perform complete blood counts weekly, particularly in patients receiving treatment longer than 2 weeks, as myelosuppression risk increases significantly with prolonged use 2
• Monitor visual acuity and color discrimination monthly in patients on extended therapy due to risk of optic neuropathy 2
• Consider prophylactic pyridoxine (vitamin B6) in patients at risk for peripheral neuropathy, including those with diabetes, alcohol abuse, or malnutrition 2

Drug Interactions and Contraindications

• Avoid concomitant use with monoamine oxidase inhibitors or within 2 weeks of discontinuing MAOIs 2
• Avoid in patients with uncontrolled hypertension, pheochromocytoma, carcinoid tumor, thyrotoxicosis, bipolar depression, schizophrenia, or acute confusional states 2
• Coadministration with adrenergic agents (pseudoephedrine, phenylpropanolamine) may cause modest blood pressure increases 4
• No dose adjustment needed when coadministered with aztreonam, gentamicin, or warfarin 4

Common Pitfalls to Avoid

• Never reduce dosing frequency to every 24 hours, as this fails to maintain adequate drug exposure for bactericidal activity 2
• Do not empirically use linezolid for catheter-related bloodstream infections; vancomycin or daptomycin are preferred first-line agents 2
• Thrombocytopenia occurs in approximately 2-7% of patients and is reversible upon discontinuation 5, 7
• Most common adverse effects include diarrhea (9.8%), headache, nausea, and gastrointestinal disturbances 7, 8