Ceftriaxone Dosing for CNS Infections
For bacterial meningitis and other CNS infections in adults, administer ceftriaxone 2 grams IV every 12 hours (total 4 grams daily), continuing this twice-daily regimen throughout the treatment course. 1, 2, 3
Standard Dosing Algorithm
Adult Patients (≥18 years)
Base dose: 2 grams IV every 12 hours for all suspected or confirmed bacterial meningitis 1, 3
Age-specific modifications:
- Patients <60 years: Ceftriaxone 2g IV every 12 hours alone 1, 3
- Patients ≥60 years: Add amoxicillin 2g IV every 4 hours to the ceftriaxone regimen to cover Listeria monocytogenes 1, 3
Resistance considerations:
- If penicillin-resistant pneumococci are suspected (recent travel from high-resistance areas), add vancomycin 15-20 mg/kg IV every 12 hours OR rifampicin 600 mg IV/PO every 12 hours to the ceftriaxone regimen 1, 3
Pediatric Patients
Meningitis dosing: 100 mg/kg/day (maximum 4 grams daily), which can be administered as:
Initial loading dose: 100 mg/kg for the first dose 4, 6
Recent evidence favors once-daily dosing in children, as it achieves higher probability of target attainment (88% vs 53% at 24 hours) compared to twice-daily dosing for common meningitis pathogens 5
Neonates (≤28 days)
Dose: 50 mg/kg once daily for most infections 3
Critical safety consideration: Administer IV doses over 60 minutes (not 30 minutes) to reduce risk of bilirubin encephalopathy 4
Contraindications: Do not use ceftriaxone in premature neonates or any neonate requiring calcium-containing IV solutions 4
Pathogen-Specific Treatment Duration
Once the causative organism is identified, adjust treatment duration accordingly:
- Meningococcal meningitis: 5 days if recovered 1, 2, 7
- Pneumococcal meningitis: 10 days if stable by day 10; extend to 14 days if slower response 1, 7
- Haemophilus influenzae: 10 days 1, 7
- Enterobacteriaceae (gram-negative bacilli): 21 days 1, 7
- Listeria monocytogenes: 21 days (requires amoxicillin, not ceftriaxone alone) 1, 7
- Culture-negative but clinically consistent: Continue empiric therapy for 14 days minimum 7
Critical Dosing Considerations
Why twice-daily dosing matters for CNS infections:
- Twice-daily administration (every 12 hours) is essential to maintain adequate CSF concentrations throughout the entire dosing interval 1, 3
- While ceftriaxone's long half-life permits once-daily dosing for many infections, CNS infections require sustained bactericidal concentrations in CSF 8, 5
- Current guidelines uniformly recommend twice-daily dosing for the first 24-48 hours at minimum to achieve rapid CSF sterilization 3
Pharmacokinetic rationale:
- CSF penetration is approximately 14-20% of plasma concentrations 8, 5
- Trough CSF levels 24 hours after dosing remain 10-100 fold higher than MIC for common pathogens with once-daily dosing 9, 10
- However, twice-daily dosing provides more consistent bactericidal activity throughout the treatment interval 1, 3
Common Pitfalls to Avoid
Do not reduce to once-daily dosing prematurely: While some research suggests once-daily dosing may be effective 9, 10, all current major guidelines recommend twice-daily dosing for CNS infections to ensure adequate CSF concentrations 1, 2, 3
Do not exceed maximum daily dose: The total daily dose should not exceed 4 grams in adults, regardless of weight 4
Do not use lower doses: Some protocols use 1-2 grams daily for non-CNS infections, but CNS infections specifically require the full 4 grams daily (2g every 12 hours) 1, 3, 4
Adjust for renal function in high-dose regimens: While standard dosing requires no adjustment, patients receiving high-dose ceftriaxone (75-100 mg/kg/day) should have dosing adapted based on estimated GFR and weight to avoid both underdosing and toxicity (target trough 20-100 mg/L) 8
Remember calcium incompatibility: Never mix ceftriaxone with calcium-containing solutions in the same IV line; flush lines thoroughly between infusions 4