What is the dosage and treatment protocol for linezolid (oxazolidinone antibiotic) for bacterial infections, including those caused by Methicillin-resistant Staphylococcus aureus (MRSA) and Vancomycin-resistant Enterococcus (VRE)?

Linezolid Treatment Indications and Dosing

Linezolid 600 mg IV or PO every 12 hours is the recommended treatment for vancomycin-resistant enterococcal (VRE) infections, methicillin-resistant Staphylococcus aureus (MRSA) infections, and other multidrug-resistant Gram-positive bacterial infections. 1

Primary Indications for Linezolid

Vancomycin-Resistant Enterococcus (VRE) Infections

• Linezolid 600 mg IV or PO every 12 hours is strongly recommended for all enterococcal infections, with treatment duration dependent on the site of infection and clinical response 1
• For VRE bacteremia specifically, linezolid achieves clinical cure rates of 67% and microbiological cure rates of 86.4% 2, 3
• For complicated urinary tract infections due to VRE, treatment duration is typically 5-7 days 4
• For uncomplicated UTIs due to VRE, alternative single-dose options include fosfomycin 3 g PO or nitrofurantoin 100 mg PO every 6 hours 1

Methicillin-Resistant Staphylococcus aureus (MRSA) Infections

• For MRSA pneumonia (both community-acquired and hospital-acquired), linezolid 600 mg IV or PO twice daily for 7-21 days is recommended as an alternative to vancomycin 1
• Linezolid achieves superior lung epithelial lining fluid concentrations compared to vancomycin, with CSF penetration as high as 66% 1
• For MRSA skin and soft tissue infections, linezolid 600 mg IV or PO twice daily is an appropriate alternative when vancomycin cannot be used 1
• For MRSA CNS infections (meningitis, brain abscess, subdural empyema), linezolid 600 mg IV or PO twice daily is recommended as an alternative to vancomycin, with CSF concentrations of 7-10 µg/mL achievable 1

Other Resistant Gram-Positive Infections

• Linezolid is effective against penicillin-resistant Streptococcus pneumoniae, including multi-drug resistant strains (MDRSP) 2
• Linezolid demonstrates activity against methicillin-resistant coagulase-negative staphylococci 5

Standard Dosing Regimens

Adults

• Standard dose: 600 mg IV or PO every 12 hours 1, 2
• Treatment duration varies by infection site: 7-21 days for pneumonia, 4-6 weeks for CNS infections, 5-7 days for complicated UTIs 1, 4
• The oral and IV formulations are bioequivalent with 100% oral bioavailability, allowing seamless transition from IV to oral therapy 1, 6

Pediatric Patients

• Children ≥12 years: 600 mg IV or PO every 12 hours 2
• Children birth to 11 years: 10 mg/kg IV or PO every 8 hours 2
• Preterm neonates <7 days old (gestational age <34 weeks): 10 mg/kg every 12 hours initially, with consideration for increasing to every 8 hours if suboptimal clinical response 2
• All neonates should receive 10 mg/kg every 8 hours by 7 days of life 2

Clinical Efficacy Data

• In the FDA approval trial for VRE infections, linezolid 600 mg every 12 hours achieved cure rates of 67% overall and 59% in patients with associated bacteremia 2
• In a compassionate-use program of 796 patients with multidrug-resistant Gram-positive infections (66.3% VRE, 22.1% MRSA), clinical cure rate was 81.4% and microbiological success was 86.4% 3
• For nosocomial pneumonia, linezolid achieved 57% cure rates in clinically evaluable patients and 59% cure rates for MRSA specifically 2

Important Pharmacokinetic Considerations

• Linezolid achieves therapeutic concentrations in most tissues including lung epithelial lining fluid (exceeds plasma levels), CSF (66% penetration), and bone 1, 6
• Optimal antibacterial effect requires time above MIC (T>MIC) for the entire treatment duration and AUC/MIC ratio >100 6
• In special populations (sepsis, burn injuries, end-stage renal disease, cystic fibrosis), pharmacokinetic variability may require dosage adjustment or addition of a third daily dose 6
• Pediatric patients exhibit wider variability in clearance and systemic exposure compared to adults; those with suboptimal clinical response (particularly with pathogens having MIC of 4 µg/mL) may require closer monitoring 2

Critical Safety Considerations and Contraindications

• Avoid tyramine-rich foods during treatment due to weak monoamine oxidase inhibitor activity 2
• Avoid concomitant use with pseudoephedrine or phenylpropanolamine, as linezolid enhances pressor response with mean maximum systolic blood pressure increases of 32-38 mm Hg 2
• Most common adverse events: gastrointestinal disturbances (9.8%), thrombocytopenia (7.4%), decreased hemoglobin/hematocrit (4.1%), and cutaneous reactions (4.0%) 3
• Thrombocytopenia risk increases with prolonged therapy beyond 2 weeks 6
• Linezolid may affect its own metabolism through mitochondrial protein synthesis inhibition, potentially leading to high plasma concentrations and increased toxicity during long-term use 6

Common Pitfalls to Avoid

• Do not use linezolid empirically for pediatric CNS infections, as CSF concentrations are variable and not consistently therapeutic in patients with ventriculoperitoneal shunts 2
• Do not assume vancomycin and linezolid have equivalent efficacy for all MRSA infections; linezolid may be superior for pneumonia due to better lung penetration 1
• Do not continue linezolid beyond necessary duration, as prolonged use (>28 days) increases risk of hematologic toxicity 6, 7
• Resistance can develop during therapy, particularly in enterococci with undrained abscesses or unremoved prosthetic devices 2