What is the recommended dose of ceftriaxone (Ceftriaxone)?

Ceftriaxone Dosing Recommendations

For most adult infections, ceftriaxone should be dosed at 1-2 grams IV/IM once daily, but central nervous system infections require 2 grams IV every 12 hours (total 4 grams daily) to ensure adequate CSF penetration throughout the dosing interval. 1, 2

Standard Adult Dosing by Infection Type

Non-CNS Infections (Once Daily Dosing)

• Uncomplicated infections: 1-2 grams IV/IM once daily for most bacterial infections 1, 2
• Uncomplicated gonorrhea: Single dose of 250 mg IM (cervical, urethral, or rectal) 1, 2
• Disseminated gonococcal infection: 1 gram IM/IV every 24 hours, continue for 24-48 hours after clinical improvement, then switch to oral therapy to complete 7 days total 1
• Skin and soft tissue infections: 1 gram every 12-24 hours depending on severity 1
• Pyelonephritis: Initial 1 gram dose, then oral therapy 1
• Lyme disease: 2 grams IV once daily for 2-4 weeks 1

CNS Infections (Twice Daily Dosing Required)

• Bacterial meningitis (empiric): 2 grams IV every 12 hours (total 4 grams daily) 1, 2
• Pneumococcal meningitis: 2 grams IV every 12 hours for 10-14 days 1
• Meningococcal meningitis: 2 grams IV every 12 hours for 5 days 1
• Gonococcal meningitis: 1-2 grams IV every 12 hours for 10-14 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

Critical point: Twice-daily dosing is mandatory for meningitis because once-daily dosing fails to maintain adequate CSF concentrations throughout the 24-hour interval, even though ceftriaxone has a long serum half-life 3. The pharmacokinetics in CSF differ substantially from serum 1.

Endocarditis

• Highly penicillin-susceptible viridans streptococci (MIC ≤0.12 μg/mL): 2 grams IV/IM once daily for 4 weeks as monotherapy 1
• Gonococcal endocarditis: 1-2 grams IV every 12 hours for at least 4 weeks 1
• HACEK organisms: 2 grams IV/IM once daily for 4 weeks (6 weeks for prosthetic valve) 1

Pediatric Dosing

Standard Pediatric Infections

• Non-CNS serious infections: 50-75 mg/kg once daily (or divided every 12 hours), maximum 2 grams daily 2
• Acute otitis media: Single IM dose of 50 mg/kg (maximum 1 gram) 2
• Meningitis: Initial dose 100 mg/kg (maximum 4 grams), then 100 mg/kg/day (maximum 4 grams daily) once daily or divided every 12 hours for 7-14 days 2

Neonatal Dosing (Special Considerations)

• Neonates 22-60 days: 50 mg/kg once daily for UTI or bacteremia 1
• Neonatal gonococcal infections: 25-50 mg/kg/day IV/IM once daily for 7 days (10-14 days if meningitis) 1, 2
• Administration: Infuse over 60 minutes in neonates to reduce risk of bilirubin encephalopathy 2

Critical contraindication: Ceftriaxone is contraindicated in premature neonates and in neonates ≤28 days requiring calcium-containing IV solutions due to risk of fatal ceftriaxone-calcium precipitation 2.

High-Dose Regimens for Resistant Organisms

Pharyngeal Gonorrhea with Elevated MICs

• Standard dose failures: Treatment failures have been documented with 250-500 mg doses for pharyngeal infections, even when MICs were technically "susceptible" (0.016-0.125 mg/L) 4
• Recommended approach: Higher doses are particularly important for pharyngeal infections due to variable pharmacokinetics in pharyngeal tissue and high protein binding (nearly 90%) in tonsillar tissue 4
• Resistant strains: For ceftriaxone-resistant strains (MIC ≥2 mg/L), twice-daily dosing of 2 grams may be required to achieve free plasma concentration of 2-3 mg/L at 24 hours 4, 1

Penicillin-Resistant Pneumococcal CNS Infections

• Add vancomycin 15-20 mg/kg IV twice daily (target trough 15-20 mg/L) OR rifampicin 600 mg twice daily to ceftriaxone 2 grams every 12 hours 1

Age-Specific Considerations for Meningitis

Adults <60 Years

• Ceftriaxone 2 grams IV every 12 hours alone (covers pneumococcus, meningococcus, H. influenzae) 1

Adults ≥60 Years

• Ceftriaxone 2 grams IV every 12 hours PLUS amoxicillin 2 grams IV every 4 hours to cover Listeria monocytogenes (ceftriaxone has no Listeria activity) 1

Administration Guidelines

Intravenous Administration

• Infusion time: 30 minutes for adults; 60 minutes for neonates 2
• Concentration: 10-40 mg/mL recommended 2
• Compatibility: Never mix with calcium-containing solutions (Ringer's, Hartmann's) due to precipitation risk 2
• Sequential administration: In non-neonates, may give calcium-containing solutions sequentially if lines thoroughly flushed between infusions 2

Intramuscular Administration

• Inject into large muscle mass with aspiration to avoid vascular injection 2
• Concentrations: 250 mg/mL or 350 mg/mL depending on volume tolerance 2

Maximum Daily Dose

• Adults and children: Do not exceed 4 grams daily 2
• No renal/hepatic adjustment needed: Standard dosing applies even with renal or hepatic impairment up to 2 grams daily in elderly patients (unless severe impairment) 2

Duration of Therapy

• General principle: Continue for at least 2 days after signs/symptoms resolve 2
• Typical duration: 4-14 days for most infections; complicated infections may require longer 2
• Streptococcus pyogenes: Minimum 10 days regardless of clinical response 2

Common Pitfalls to Avoid

1. Using once-daily dosing for meningitis: This is inadequate for CNS penetration; always use twice-daily dosing for any CNS infection 1, 3

2. Underdosing pharyngeal gonorrhea: The 250 mg dose has documented failures; consider higher doses for pharyngeal infections, especially if MICs are elevated 4

3. Forgetting Listeria coverage: In patients ≥60 years with meningitis, ceftriaxone alone is insufficient; must add ampicillin or amoxicillin 1

4. Mixing with calcium: Fatal precipitates can form; never co-administer with calcium-containing solutions, especially in neonates 2

5. Assuming 1 gram is adequate for sepsis: Recent pharmacokinetic data suggests 1 gram once daily is unlikely to achieve therapeutic exposure in >90% of septic patients with normal renal function; 2 grams once daily is preferred 5