What is the recommended ceftriaxone dosing regimen for a pediatric patient with bacterial meningitis?

Pediatric Meningitic Dose of Ceftriaxone

For pediatric bacterial meningitis, administer ceftriaxone 80–100 mg/kg/day divided every 12 hours (or as a single daily dose of 100 mg/kg), with a maximum of 4 grams per day, for 7–10 days depending on the causative organism. 1

Age-Stratified Dosing Algorithm

Neonates 8–21 Days Old

• Do NOT use ceftriaxone as monotherapy 1
• Use ampicillin 300 mg/kg/day divided every 6 hours PLUS ceftazidime 150 mg/kg/day divided every 8 hours 1
• Ceftriaxone is contraindicated in hyperbilirubinemic neonates due to kernicterus risk 2

Neonates 22–28 Days Old

• Ampicillin 300 mg/kg/day divided every 6 hours PLUS ceftazidime 150 mg/kg/day divided every 8 hours 1
• Ceftriaxone may be considered but ampicillin + ceftazidime remains preferred to cover Listeria monocytogenes 1

Infants and Children 29 Days to 18 Years

• Ceftriaxone 80–100 mg/kg/day (maximum 4 g/day) 1
• Can be administered as:
  • 50 mg/kg every 12 hours (twice daily) 1, 3
  • 100 mg/kg once daily 1, 2, 4, 5

Dosing Frequency: Once Daily vs. Twice Daily

Recent pharmacokinetic evidence supports once-daily dosing (100 mg/kg) over twice-daily dosing (50 mg/kg every 12 hours) for empirical treatment. 6

• Once-daily dosing achieves 88% probability of target attainment at 24 hours versus 53% for twice-daily dosing (for MIC 1 mg/L) 6
• Both regimens achieve 100% target attainment at steady state 6
• CSF penetration is approximately 20% of serum concentrations 6
• Mean CSF concentrations with 100 mg/kg once daily: 6.4 mcg/mL at 3.3 hours post-dose 3
• Mean CSF concentrations with 50 mg/kg twice daily: 5.6 mcg/mL at 3.7 hours post-dose 3

Clinical studies demonstrate equivalent efficacy between once-daily and twice-daily regimens, with once-daily offering practical advantages. 4, 5, 7

Duration of Therapy by Pathogen

Organism	Duration	Citation
Neisseria meningitidis	5–7 days	[1,2]
Haemophilus influenzae	7–10 days	[1,2]
Streptococcus pneumoniae	10–14 days	[1,2]
Gram-negative enteric bacilli	21 days	[2]

Critical Dosing Considerations

Maximum Dose Limits

• Absolute maximum: 4 grams per day regardless of weight 1, 2
• For a 50 kg child: dose would be capped at 4 g/day, not 5 g/day (100 mg/kg) 1

Adjunctive Therapy

• Add vancomycin 60 mg/kg/day divided every 8 hours if Streptococcus pneumoniae is suspected or confirmed, targeting trough levels of 15–20 mg/mL 1
• Vancomycin covers penicillin-resistant pneumococci (MIC >0.12 mg/L) 1, 2

Dexamethasone

• Administer dexamethasone 0.15 mg/kg every 6 hours for 2–4 days for H. influenzae type b meningitis 1
• Give 10–20 minutes before or concurrent with first antibiotic dose 1
• For pneumococcal meningitis, dexamethasone use remains controversial; consider on case-by-case basis 1

Route of Administration

• Intravenous administration is strongly preferred for meningitis 1, 2
• Intramuscular administration is acceptable if IV access cannot be established 4, 5
• Infuse IV doses over 30 minutes 8

Pharmacokinetic Parameters in Pediatric Meningitis

From FDA labeling and clinical studies 8, 3:

• Elimination half-life: 4.3–5.8 hours 8, 3
• Plasma clearance: 49–60 mL/hr/kg 8, 3
• Volume of distribution: 338–387 mL/kg 8, 3
• CSF concentrations (inflamed meninges): 5.6–6.4 mcg/mL (range 1.3–44 mcg/mL) 8, 3
• Time to peak CSF concentration: 3.3–3.7 hours post-dose 8, 3

Common Pitfalls to Avoid

1. Do not use ceftriaxone in neonates <28 days as monotherapy – must add ampicillin for Listeria coverage 1
2. Do not use ceftriaxone in hyperbilirubinemic or premature neonates – risk of kernicterus from bilirubin displacement 2
3. Do not underdose – 50 mg/kg once daily is insufficient; use either 50 mg/kg twice daily OR 100 mg/kg once daily 1, 6
4. Do not omit vancomycin for suspected pneumococcal meningitis – resistance rates necessitate empiric dual coverage 1, 2
5. Do not give dexamethasone after antibiotics have started – it is ineffective if not given before or with first antibiotic dose 1
6. Neither once-daily nor twice-daily ceftriaxone is adequate for Staphylococcus aureus meningitis (MIC 4 mg/L) – alternative agents required 6

Practical Dosing Example

For a 5-year-old child weighing 18 kg with suspected bacterial meningitis:

• Ceftriaxone: 100 mg/kg/day = 1,800 mg once daily IV (or 900 mg every 12 hours) 1, 6
• Vancomycin: 60 mg/kg/day = 1,080 mg/day divided into 360 mg every 8 hours IV 1
• Dexamethasone: 0.15 mg/kg every 6 hours = 2.7 mg every 6 hours for 2–4 days (if H. influenzae confirmed) 1
• Duration: 7–10 days for H. influenzae, 10–14 days for S. pneumoniae 1, 2