What is the recommended dosing of cefazolin (a first-generation cephalosporin antibiotic) for central nervous system (CNS) infections?

Cefazolin Dosing for Central Nervous System Infections

For central nervous system (CNS) infections, cefazolin should be dosed at 100 mg/kg/day IV divided every 8 hours up to a maximum of 12 g daily. 1

Recommended Dosing Regimen

• Standard dosing for CNS infections: 100 mg/kg/day IV divided every 8 hours (maximum 12 g daily) 1
• For optimized CNS penetration in severe infections: Consider 2 g IV every 6 hours or continuous infusion of 8-10 g daily 2
• Pediatric dosing: 100 mg/kg/day IV divided every 8 hours 1

Evidence-Based Rationale

• Cefazolin has been established as an alternative to antistaphylococcal penicillins for methicillin-susceptible Staphylococcus aureus (MSSA) CNS infections 2
• The American Heart Association guidelines recommend cefazolin at 100 mg/kg/day IV divided every 8 hours for staphylococcal infections that may involve the CNS 1
• Recent evidence suggests that dose-optimized cefazolin regimens may be effective for CNS infections due to its favorable safety profile compared to antistaphylococcal penicillins 2

Special Considerations

Renal Adjustment

• Dose adjustment is critical in renal impairment to prevent neurotoxicity 3, 4
• High CSF concentrations of cefazolin (>34 μg/mL) have been associated with seizures in patients with renal dysfunction 3, 4
• Monitor for signs of neurotoxicity including confusion, muscle twitches, and seizures in patients with impaired renal function 4

Alternative Agents for CNS Infections

• For MRSA CNS infections: Vancomycin 15-20 mg/kg/dose IV every 8-12 hours (adults) or 15 mg/kg/dose IV every 6 hours (pediatrics) 1
• Some experts recommend adding rifampin 600 mg daily or 300-450 mg twice daily to vancomycin for CNS infections 1
• Alternative agents include:
  • Linezolid 600 mg PO/IV twice daily (adults) or 10 mg/kg/dose PO/IV every 8 hours (pediatrics) 1
  • TMP-SMX 5 mg/kg/dose IV every 8-12 hours 1

Monitoring Parameters

• For patients receiving high-dose cefazolin for CNS infections, monitor:
  • Clinical response (temperature, white blood cell count, neurological status) 5
  • Renal function tests to guide dosing adjustments 3, 4
  • Signs of neurotoxicity, particularly in patients with renal impairment 3, 4

Duration of Therapy

• Meningitis: 2 weeks of IV therapy 1
• Brain abscess, subdural empyema, spinal epidural abscess: 4-6 weeks of IV therapy 1
• Septic thrombosis of cavernous or dural venous sinus: 4-6 weeks of IV therapy 1

Important Caveats

• CSF penetration of cefazolin increases with multiple dosing and in the presence of inflammation 4
• In patients with normal renal function, cefazolin typically achieves 5-10% penetration into CSF 4
• For CNS shunt infections, shunt removal is recommended until CSF cultures are repeatedly negative 1
• Surgical drainage of focal abscesses is recommended whenever possible to improve antibiotic efficacy 1