What is the recommended dose and frequency of ceftriaxone (Ceftriaxone) administration?

Ceftriaxone Dosing and Frequency

For most adult infections, administer ceftriaxone 1-2 grams once daily IV or IM, but for serious CNS infections including meningitis, you must use 2 grams every 12 hours to ensure adequate CSF concentrations throughout the dosing interval. 1, 2

Standard Adult Dosing by Infection Type

Uncomplicated Infections

• Uncomplicated gonococcal infections: 250 mg IM as a single dose 1, 2
• Skin and soft tissue infections: 1 gram every 12-24 hours depending on severity 1
• Urinary tract infections: 1 gram IM/IV every 24 hours initially, then consider oral therapy 1

Serious Infections Requiring Higher Dosing

• Bacterial meningitis: 2 grams IV every 12 hours (total 4 grams daily) for 10-14 days 1, 2
• Disseminated gonococcal infection: 1 gram IM/IV every 24 hours, continue for 24-48 hours after improvement, then switch to oral therapy to complete one week 1
• Gonococcal meningitis/endocarditis: 1-2 grams IV every 12 hours for 10-14 days (meningitis) or at least 4 weeks (endocarditis) 1
• HACEK endocarditis: 2 grams per 24 hours IV/IM in 1 dose for 4 weeks (6 weeks for prosthetic valve) 1

Pathogen-Specific Meningitis Dosing

• Pneumococcal meningitis: 2 grams IV every 12 hours for 10-14 days, extend if patient not recovered by day 10 1
• Meningococcal meningitis: 2 grams IV every 12 hours for 5 days 1
• Haemophilus influenzae meningitis: 2 grams IV every 12 hours for 10 days 1
• Enterobacteriaceae CNS infections: 2 grams IV every 12 hours for 21 days 1

Pediatric Dosing

Neonates (≤28 days)

• Standard infections: 50 mg/kg once daily IV/IM 1, 2
• Meningitis: 100 mg/kg once daily (not to exceed 4 grams) 2
• Critical warning: Contraindicated in neonates requiring calcium-containing IV solutions due to precipitation risk 2
• Administration: Infuse over 60 minutes in neonates to reduce bilirubin encephalopathy risk 2

Infants and Children

• Skin/soft tissue infections: 50-75 mg/kg once daily (max 2 grams) 2
• Acute otitis media: 50 mg/kg IM single dose (max 1 gram) 2
• Serious infections (non-meningitis): 50-75 mg/kg divided every 12 hours (max 2 grams daily) 2
• Meningitis: 100 mg/kg/day (max 4 grams daily), can be given once daily or divided every 12 hours 2
• Gonococcal infections in children <45 kg: 125 mg IM single dose for uncomplicated; 50 mg/kg daily (max 1 gram) for 7 days for bacteremia/arthritis, 10-14 days for meningitis 1

Critical Dosing Considerations

When Twice-Daily Dosing is Mandatory

The long half-life of ceftriaxone allows once-daily dosing for most infections, but CNS infections are the critical exception. 3 Twice-daily dosing (every 12 hours) is absolutely required for:

• All bacterial meningitis cases during at least the first 24 hours to achieve rapid CSF sterilization 1
• Infections with high MICs or resistant strains 3
• Vertebral discitis with epidural involvement 1

Special Population Adjustments

• Elderly patients (≥60 years with meningitis): Add amoxicillin 2 grams IV every 4 hours to ceftriaxone 2 grams every 12 hours to cover Listeria monocytogenes 1
• Penicillin-resistant pneumococci: Add vancomycin 15-20 mg/kg IV twice daily (target trough 15-20 mg/mL) or rifampin 600 mg twice daily to ceftriaxone regimen 1
• Renal/hepatic impairment: No dosage adjustment necessary unless both severe renal and hepatic impairment present 2

Resistant Organisms

For pharyngeal gonorrhea with elevated MICs, treatment failures occur with standard 250-500 mg doses; consider twice-daily dosing of 2 grams to achieve free plasma concentration of 2-3 mg/L at 24 hours 1

Administration Guidelines

Intramuscular Administration

• Inject well within the body of a relatively large muscle 2
• Aspirate to avoid unintentional vascular injection 2
• Reconstitute to 250 mg/mL or 350 mg/mL concentration 2

Intravenous Administration

• Infuse over 30 minutes for adults 2
• Infuse over 60 minutes for neonates to reduce bilirubin encephalopathy risk 2
• Use concentrations between 10-40 mg/mL 2
• Never mix with calcium-containing solutions (Ringer's, Hartmann's) due to precipitation risk 2

Common Pitfalls to Avoid

1. Using once-daily dosing for meningitis: This is inadequate for CNS penetration; always use every 12-hour dosing for meningitis 1, 3
2. Forgetting to add antichlamydial coverage: When treating gonococcal infections, add appropriate coverage if Chlamydia trachomatis not ruled out 1, 2
3. Underdosing pharyngeal gonorrhea: Standard 250 mg doses have documented failures; use higher doses for pharyngeal infections 1
4. Administering to hyperbilirubinemic neonates: Ceftriaxone displaces bilirubin from albumin binding sites 2
5. Mixing with calcium-containing solutions: Can cause fatal precipitation 2

Maximum Dosing Limits

• Adults: Do not exceed 4 grams daily 2
• Pediatrics: Do not exceed adult dosing even when weight-based calculations suggest higher doses 4, 2