What is the central nervous system (CNS) penetration of Linezolid (oxazolidinone antibiotic)?

From the Guidelines

Linezolid has good central nervous system (CNS) penetration, with CSF penetration as high as 66%, making it a valuable option for treating CNS infections. The drug achieves cerebrospinal fluid (CSF) concentrations of 7–10 lg/mL and 2.5–6.0 lg/mL for peak and trough concentrations, respectively 1. This high penetration is due to linezolid's ability to cross the blood-brain barrier effectively. For CNS infections, the standard adult dosing of 600 mg twice daily is typically sufficient to achieve therapeutic concentrations in the CSF, as recommended by the Infectious Diseases Society of America 1.

Key Points

• Linezolid is particularly useful for treating CNS infections caused by resistant gram-positive organisms, including methicillin-resistant Staphylococcus aureus (MRSA) 1.
• When treating CNS infections, monitoring for linezolid's adverse effects is important, particularly with prolonged therapy (beyond 2 weeks), as patients may develop myelosuppression, peripheral neuropathy, or optic neuritis.
• Regular complete blood counts should be performed, especially when treatment extends beyond 14 days.

CNS Infection Treatment

• Linezolid 600 mg PO/IV twice daily is recommended as an alternative treatment for CNS infections, including meningitis and brain abscess 1.
• The choice of treatment should be based on the severity of the infection, the susceptibility of the organism, and the patient's clinical condition.
• Neurosurgical evaluation for incision and drainage is recommended for brain abscess, subdural empyema, and spinal epidural abscess 1.

From the FDA Drug Label

Pharmacokinetic information generated in pediatric patients with ventriculoperitoneal shunts showed variable cerebrospinal fluid (CSF) linezolid concentrations following single and multiple dosing of linezolid; therapeutic concentrations were not consistently achieved or maintained in the CSF The CNS penetration of linezolid is variable and therapeutic concentrations are not consistently achieved or maintained in the cerebrospinal fluid (CSF) 2.

• Key points:
  • Variable CSF linezolid concentrations
  • Therapeutic concentrations not consistently achieved or maintained in CSF
  • Use of linezolid for empiric treatment of pediatric patients with central nervous system infections is not recommended 2

From the Research

Linezolid CNS Penetration

• Linezolid is a valuable treatment option for central nervous system (CNS) infections caused by multidrug-resistant Gram-positive micro-organisms 3.
• Studies have shown that linezolid demonstrates good penetration into the CNS, with a median CSF/plasma ratio of 0.77 3 and a mean penetration ratio for the AUC for CSF to the AUC for serum of 0.66 4.
• However, high interindividual pharmacokinetic variability has been observed, which may result in subtherapeutic antibiotic exposure 3, 5.
• The penetration of linezolid into cerebral interstitial fluid (ISF) has also been studied, with a median penetration ratio of 0.5 for cerebral ISF and 0.92 for CSF 5.
• Cerebral ISF concentrations have been found to correlate well with plasma and CSF levels, with a median fAUC0-24/MIC ratio of ≥100 in plasma and CSF for MICs of ≤0.5 mg/L, and in cerebral ISF for MICs of ≤0.25 mg/L 5.
• Therapeutic drug monitoring has been suggested as a useful strategy to optimize treatment in some patients, due to the variability in linezolid concentrations in CSF and plasma 3, 6, 7.
• Some studies have reported cases where linezolid may not reach therapeutic concentrations in cerebrospinal fluid, highlighting the need for monitoring drug levels 7.