From the Guidelines
Linezolid is a valuable option for the treatment of central nervous system (CNS) infections, particularly those caused by resistant gram-positive organisms, due to its excellent CNS penetration and achievable bactericidal concentrations in CSF. The evidence supporting linezolid's use in CNS infections comes from case reports and limited clinical studies, including a study published in Clinical Infectious Diseases in 2011 1, which highlights the challenges of treating MRSA CNS infections due to the blood-brain barrier and limited penetration of systemically administered antibiotics.
Key Points
- Linezolid achieves good CSF penetration, as high as 66%, with CSF peak and trough concentrations of 7–10 lg/mL and 2.5–6.0 lg/mL, respectively 1.
- The typical dosing regimen is 600mg twice daily, either intravenously or orally due to its nearly 100% bioavailability.
- Treatment duration depends on the specific infection but generally ranges from 2-6 weeks.
- Monitoring for adverse effects is essential during extended therapy, including weekly complete blood counts to detect potential bone marrow suppression, particularly thrombocytopenia, which becomes more common after 2 weeks of treatment.
Comparison with Other Antibiotics
- Vancomycin has poor CSF penetration, approximately 1% and 5% for uninflamed and inflamed meninges, respectively, with maximum CSF concentrations of 2–6 lg/mL 1.
- TMP-SMX has similar CSF penetration for uninflamed and inflamed meninges, 13%–53% for TMP and 17%–63% for SMX; CSF concentrations are 1.9–5.7 lg/mL for TMP and 20–63 lg/mL for SMX after a 10 mg/kg/day dosage and a 50 mg/kg/day dosage, respectively 1.
- Rifampin has CSF penetration of 22% and is similar for inflamed and non-inflamed meninges, and bactericidal concentrations are achievable in CSF 1.
Clinical Implications
- Linezolid is not FDA-approved specifically for CNS infections, but its pharmacokinetic properties and clinical experience support its use as a valuable option for multi-drug resistant gram-positive CNS infections, particularly when first-line agents fail or are contraindicated.
- The use of linezolid in CNS infections should be guided by susceptibility testing and clinical judgment, taking into account the potential risks and benefits of treatment.
From the Research
Effectiveness of Linazole in CNS Infections
- There is no direct evidence provided in the studies to support the effectiveness of linazole in central nervous system (CNS) infections.
- However, one study 2 mentions linezolid as an anti-infective that reaches a CSF-to-serum ratio of the areas under the curves close to 1.0, making it valuable for the treatment of CNS infections.
- Another study 3 found that more than 90% of Staphylococcus aureus strains showed susceptibility to linezolid, suggesting its potential effectiveness against certain bacterial CNS infections.
Alternative Antibiotics for CNS Infections
- Ceftriaxone is widely used to treat community-acquired CNS bacterial infections, and high-dose ceftriaxone has been shown to be well tolerated in adults 4.
- Colistin is considered an effective and safe option for CNS infections caused by multi-drug resistant Gram-negative bacteria, and can be administered intrathecally or intraventricularly 5.
- The choice of antibiotic for CNS infections should be based on the susceptibility of the isolated microorganism and the treatment's pharmacokinetic properties, including its ability to penetrate the blood-brain barrier 6, 2.