What are the indications, dosing, treatment duration, and monitoring recommendations for linezolid in adult and pediatric patients?

Linezolid: Indications, Dosing, Duration, and Monitoring

Indications

Linezolid is indicated for serious gram-positive infections including MRSA pneumonia, complicated skin and soft tissue infections, bacteremia, bone/joint infections, and vancomycin-resistant enterococcal infections. 1

Specific FDA-Approved Indications:

• Complicated skin and skin structure infections 2
• Community-acquired pneumonia (including concurrent bacteremia) 2
• Nosocomial pneumonia 2
• Vancomycin-resistant Enterococcus faecium infections (including concurrent bacteremia) 2
• Uncomplicated skin and skin structure infections 2

IDSA Guideline-Supported Uses for MRSA:

• Pneumonia: Severe community-acquired or hospital-acquired MRSA pneumonia, particularly with necrotizing/cavitary infiltrates or empyema 1
• Bacteremia and endocarditis: Alternative to vancomycin 1
• Bone and joint infections: Osteomyelitis and septic arthritis 1
• CNS infections: Meningitis, brain abscess, subdural empyema, spinal epidural abscess 1

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Dosing

Adult Dosing

The standard adult dose is 600 mg IV or oral every 12 hours for all serious infections. 2, 1

• Complicated SSTI, pneumonia, bacteremia, bone/joint infections, CNS infections: 600 mg IV or PO every 12 hours 1, 2
• Uncomplicated SSTI: 400 mg PO every 12 hours 2
• No renal dose adjustment required: 600 mg every 12 hours regardless of renal function, including dialysis 3
• Oral and IV formulations are interchangeable with 100% bioavailability 2, 4

Pediatric Dosing

Pediatric patients require weight-based dosing with higher mg/kg doses than adults due to increased clearance. 2, 5

Neonates (Birth to 7 Days):

• Preterm neonates <7 days old (gestational age <34 weeks): 10 mg/kg IV or PO every 12 hours 2
• All neonates by 7 days of life: 10 mg/kg IV or PO every 8 hours 2

Infants and Children (Birth through 11 Years):

• Most infections: 10 mg/kg IV or PO every 8 hours (not to exceed 600 mg/dose) 2, 1
• Uncomplicated SSTI:
  • <5 years: 10 mg/kg PO every 8 hours 2
  • 5-11 years: 10 mg/kg PO every 12 hours 2

Adolescents (≥12 Years):

• Use adult dosing: 600 mg IV or PO every 12 hours 2, 1

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Treatment Duration

Treatment duration ranges from 7-28 days depending on infection type and severity. 2, 1

Specific Durations by Infection:

• Complicated SSTI: 10-14 days 1, 2
• Uncomplicated SSTI: 10-14 days 1, 2
• Pneumonia (community-acquired, nosocomial, MRSA): 7-21 days depending on extent of infection 1, 2
• Bacteremia: 14-28 days 1, 2
• Vancomycin-resistant enterococcal infections: 14-28 days 1, 2
• Bone and joint infections: Typically 4-6 weeks (not explicitly stated in FDA label but per IDSA guidelines) 1
• CNS infections: Extended duration based on clinical response 1

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Monitoring Recommendations

Hematologic Monitoring

Weekly complete blood counts (CBC) are mandatory, especially for treatment exceeding 2 weeks, due to risk of myelosuppression. 6, 7

• Baseline CBC before initiating therapy 6
• Weekly CBC for the first 2 months, then monthly if stable 6
• More frequent monitoring (daily) if WBC drops to 2000-3000/mm³ or ANC drops to 1000-1500/mm³ 6
• Hematology consultation if WBC <2000/mm³ or ANC <1000/mm³ 6
• Thrombocytopenia, anemia, and neutropenia can occur, particularly with doses >600 mg/day and prolonged treatment 6, 7

Neurological Monitoring

Monthly visual acuity and color discrimination testing are recommended to detect optic neuritis. 6

• Monthly screening for peripheral neuropathy symptoms 6, 7
• Neurological toxicity typically occurs after 12-20 weeks of treatment 6, 7
• May be irreversible or only partially reversible 6, 7

Metabolic Monitoring

Monitor lactate levels periodically during long-term use due to risk of lactic acidosis from mitochondrial toxicity. 6, 7

• Obtain arterial blood gas if venous lactate is abnormal 6
• Risk increases with concurrent use of stavudine or zidovudine 6

Drug Interaction Monitoring

Linezolid is contraindicated with MAO inhibitors and serotonergic agents due to risk of serotonin syndrome. 6, 7

• Avoid tyramine-rich foods due to MAO inhibitor properties 6
• Baseline vital signs, mental status, and neurological examination if combination with serotonergic drugs cannot be avoided 6
• Avoid ondansetron when possible; consider metoclopramide as alternative antiemetic 6

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Special Populations and Dosing Adjustments

Renal Impairment

No dose adjustment required for any degree of renal insufficiency, including dialysis. 3, 2

Hepatic Impairment

No dose adjustment required for mild to moderate hepatic impairment. 4

• Use with caution and close monitoring in severe liver disease 6

Pregnancy and Breastfeeding

Use with caution in pregnancy (risk-benefit assessment required); contraindicated in breastfeeding. 6

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Common Pitfalls and Caveats

Dosing Errors

• Do not underdose pediatric patients: Children require higher mg/kg doses than adults due to increased clearance 5, 8
• Children <10 years may be particularly susceptible to myelosuppression at standard doses 6

Toxicity Management

• Reducing dose from 1200 mg to 600 mg daily reduces adverse events from 74.5% to 46.7% without compromising efficacy 6
• Consider dose reduction to 300 mg once daily if serious adverse effects develop 6
• Myelosuppression is more responsive to dose reduction than neurotoxicity 6

Contraindications

Absolute contraindications include: 6

• Concurrent use with MAO inhibitors or serotonergic agents
• Uncontrolled hypertension, pheochromocytoma, thyrotoxicosis
• Bipolar depression, schizophrenia, acute confusional states
• Breastfeeding

Resistance Considerations

• Pediatric patients with pathogens having MIC of 4 µg/mL may have suboptimal response; consider lower systemic exposure and severity of infection 2