What is the recommended dosage of Linezolid (oxazolidinone antibiotic) for treating infections, particularly in patients with impaired renal function?

Linezolid Dosage Recommendations

For adult patients with normal renal function, linezolid should be administered at 600 mg intravenously or orally every 12 hours. 1, 2, 3

Standard Dosing Recommendations by Patient Population

Adults

• Normal renal function: 600 mg IV/PO every 12 hours 1, 4
• Severe renal impairment: 600 mg IV/PO every 12 hours (no dose adjustment needed based on renal function, but monitor for metabolite accumulation) 2, 3
• Hemodialysis: Administer linezolid after hemodialysis session (approximately 30% of dose is removed during a 3-hour hemodialysis session) 2
• Mild-to-moderate hepatic impairment: No dose adjustment needed 2, 3

Pediatric Patients

• Birth to 11 years: 10 mg/kg every 8 hours IV/PO 2
• 12 years and older: 600 mg every 12 hours IV/PO (adult dosing) 2

Dosing for Specific Infections

Vancomycin-Resistant Enterococcus (VRE) Infections

• 600 mg IV/PO every 12 hours 1
• Duration depends on site of infection and clinical response 1
• Strong recommendation, low quality of evidence 1

Infective Endocarditis

• 600 mg IV/PO every 12 hours 1
• Duration: >6 weeks 1
• Class IIb recommendation; Level of Evidence C 1

Tuberculosis (MDR/RR-TB) Regimens

• 600 mg daily for 26 weeks as part of BPaLM regimen (bedaquiline, pretomanid, linezolid, moxifloxacin) 1
• Consider reducing to 300 mg daily if toxicity develops, though 600 mg daily is preferred 1

MRSA Infections

• Skin and soft tissue infections: 600 mg IV/PO every 12 hours for 7-14 days 4
• Bacteremia: 600 mg IV/PO every 12 hours for 10-14 days 4

Monitoring and Safety Considerations

Therapeutic Drug Monitoring

• Consider therapeutic drug monitoring in critically ill patients due to high variability in serum concentrations 5, 6
• Potentially subtherapeutic concentrations (AUC24 <200 mg*h/L and Cmin <2 mg/L) observed in up to 63% of critically ill patients receiving standard dosing 6
• Potentially toxic levels (AUC24 >400 mg*h/L and Cmin >10 mg/L) observed in some patients 6

Adverse Effects to Monitor

• Thrombocytopenia (7.4% of cases) 7
• Decreased hemoglobin/hematocrit levels (4.1% of cases) 7
• Gastrointestinal disturbances (9.8% of cases) 7
• Peripheral and optic neuropathy with prolonged use 5

Special Considerations

Renal Impairment

• No dose adjustment is required based on renal function 2, 3
• However, metabolites accumulate in renal impairment, with accumulation increasing with severity of renal dysfunction 2, 3
• Use with caution in severe renal impairment due to 7-8 fold higher exposure to primary metabolites 8

Drug Interactions

• Linezolid is a reversible, nonselective inhibitor of monoamine oxidase 3
• Avoid concurrent administration with adrenergic and serotonergic agents 3
• No significant interaction with warfarin, aztreonam, or gentamicin 2, 3
• Rifampin can decrease linezolid concentrations (21% decrease in Cmax, 32% decrease in AUC) 3

Clinical Efficacy

• Overall clinical cure rates of 81.4% and microbiological cure rates of 86.4% in VRE infections 1
• Comparable efficacy to daptomycin in VRE bacteremia 1
• Effective for complicated skin and skin structure infections with similar efficacy to longer treatment courses 9

Remember that while no dose adjustment is needed for renal impairment, careful monitoring is essential due to metabolite accumulation. For critically ill patients, therapeutic drug monitoring may help optimize dosing given the high variability in serum concentrations observed in this population.