What is the recommended dosing regimen for ceftriaxone (a cephalosporin antibiotic) in a typical adult patient with a bacterial infection and potentially impaired renal function?

Ceftriaxone Dosing for Adult Bacterial Infections

For most adult bacterial 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

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
• Disseminated gonococcal infection: 1 gram IM/IV every 24 hours initially, continue for 24-48 hours after improvement, then switch to oral therapy to complete 7 days total 1
• Uncomplicated gonorrhea: Single dose of 250 mg IM (though resistance patterns may require higher doses) 1
• Endocarditis (highly susceptible organisms): 2 grams IV/IM once daily for 4 weeks (6 weeks for prosthetic valve) 1
• Lyme disease: 2 grams IV once daily for 2-4 weeks 1

CNS Infections (Twice-Daily Dosing Required)

All meningitis and CNS infections require 2 grams IV every 12 hours (total 4 grams daily): 1

• Bacterial meningitis (empiric): 2 grams IV every 12 hours 1
• 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
• Enterobacteriaceae CNS infections: 2 grams IV every 12 hours for 21 days 1
• Haemophilus influenzae meningitis: 2 grams IV every 12 hours for 10 days 1
• Gonococcal meningitis: 1-2 grams IV every 12 hours for 10-14 days 1

The twice-daily dosing for CNS infections is critical because it ensures sustained therapeutic CSF concentrations throughout the 24-hour period, which cannot be reliably achieved with once-daily dosing. 1

Special Dosing Considerations

Age-Related Adjustments

• Patients ≥60 years with suspected meningitis: Add amoxicillin 2 grams IV every 4 hours to the ceftriaxone regimen to cover Listeria monocytogenes 1

Resistant Organisms

• Penicillin-resistant pneumococci: Continue ceftriaxone 2 grams every 12 hours AND add vancomycin 15-20 mg/kg IV every 12 hours (target trough 15-20 μg/mL) or rifampicin 600 mg twice daily 1
• Pharyngeal gonorrhea with elevated MICs: Treatment failures documented with 250-500 mg doses; higher doses (potentially 2 grams twice daily) may be required to achieve adequate free plasma concentrations 1

Renal and Hepatic Impairment

No dosage adjustment is necessary for patients with renal or hepatic impairment alone. 2 The maximum daily dose should not exceed 4 grams regardless of renal function 2. This is a critical advantage of ceftriaxone over other cephalosporins and makes it particularly useful in critically ill patients with multiorgan dysfunction.

Administration Guidelines

Intravenous Administration

• Standard infusion time: 30 minutes for concentrations between 10-40 mg/mL 2
• Neonates only: Administer over 60 minutes to reduce risk of bilirubin encephalopathy 2
• Reconstitution: Use appropriate IV diluents; never use calcium-containing solutions (Ringer's, Hartmann's) as particulate formation will occur 2

Intramuscular Administration

• Painful injection: Patients should be warned that IM ceftriaxone is painful 1
• Injection technique: Inject deep into large muscle mass with aspiration to avoid intravascular injection 2
• IM and IV routes are interchangeable for most indications, with plasma concentrations equalizing by 2.5 hours 3

Critical Pitfalls to Avoid

Dosing Errors

• Never use once-daily dosing for CNS infections during the first 24-48 hours, as rapid CSF sterilization requires sustained therapeutic levels 1
• Do not underdose resistant organisms: Treatment failures with 250-500 mg doses are well-documented, particularly for pharyngeal infections 1
• Never exceed 4 grams total daily dose even in severe infections 2

Duration Errors

• Enterobacteriaceae CNS infections require 21 days, not the 10-14 days used for pneumococcal disease—this is a common and dangerous error 1, 4
• Meningococcal meningitis can be safely stopped at 5 days if clinically recovered 1
• Pneumococcal meningitis requires 10-14 days, with longer duration if clinical response is delayed 1

Combination Therapy Errors

• Never use vancomycin alone for CNS infections due to poor CSF penetration, especially with dexamethasone use—always combine with ceftriaxone 4
• Always add antichlamydial coverage for gonococcal infections if Chlamydia trachomatis is not ruled out 1

Calcium Interaction

• Absolutely contraindicated in neonates ≤28 days receiving or expected to receive calcium-containing IV solutions due to fatal precipitation risk 2
• In patients other than neonates, ceftriaxone and calcium-containing solutions may be given sequentially if lines are thoroughly flushed 2

Evidence Quality Assessment

The strongest and most recent evidence comes from CDC and IDSA guidelines (2025-2026) consistently recommending twice-daily dosing for CNS infections. 1 A 2023 Swiss study suggested that once-daily dosing (2 grams every 24 hours) may have similar outcomes to twice-daily dosing for penicillin-susceptible S. pneumoniae meningitis 5, but this contradicts all major guideline recommendations and should not change practice, as guidelines uniformly prioritize twice-daily dosing to ensure adequate CSF concentrations throughout the treatment period. 1

The pharmacokinetic data supporting once-daily dosing for non-CNS infections is robust, with plasma half-life of 7-8 hours and sustained concentrations exceeding MICs for most organisms for 24 hours after a single 1-gram dose 3, 6. However, CSF penetration is variable and concentration-dependent, making twice-daily dosing essential for CNS infections despite the long half-life. 1