What is the recommended dose of ceftriaxone (a third-generation cephalosporin antibiotic) for a patient with a suspected bacterial infection?

Ceftriaxone Dosing for Bacterial Infections

For most adult bacterial infections, administer ceftriaxone 1-2 grams IV/IM every 24 hours, but for central nervous system infections (meningitis, epidural abscess) or endocarditis, you must use 2 grams IV every 12 hours to ensure adequate tissue penetration and sustained therapeutic concentrations. 1, 2

Adult Dosing Algorithm by Infection Site and Severity

Central Nervous System Infections (Highest Priority)

• Bacterial meningitis: 2 grams IV every 12 hours (total 4 grams daily) for 10-14 days 1
• Pneumococcal meningitis: 2 grams IV every 12 hours for 10-14 days, extending if clinical response is delayed 1
• Meningococcal meningitis: 2 grams IV every 12 hours for 5 days 1
• Vertebral discitis with epidural involvement: 2 grams IV every 12 hours, following the same principles as meningitis for adequate CNS penetration 1
• Add vancomycin 15-20 mg/kg IV every 8-12 hours if penicillin-resistant pneumococci or MRSA is suspected 1
• Add ampicillin 2 grams IV every 4 hours for patients ≥60 years to cover Listeria monocytogenes 1

Endocarditis

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

Complicated Intra-Abdominal Infections

• Standard dosing: 1-2 grams every 12-24 hours 3, 2
• The Surgical Infection Society and IDSA guidelines support this range for empiric coverage of mixed aerobic-anaerobic infections 3
• Add metronidazole 500 mg every 8-12 hours for enhanced anaerobic coverage 3

Community-Acquired Pneumonia

• Standard dosing: 1 gram IV every 24 hours is sufficient in regions with low penicillin-resistant S. pneumoniae prevalence 4
• A retrospective study of 3,989 patients showed 1 gram daily had similar 30-day mortality to 2 grams daily (14.7% vs 16.0%, p=0.24), with lower C. difficile rates and shorter hospital stays 4
• Use 2 grams daily if severe pneumonia or high local resistance rates 2

Gonococcal Infections

• Uncomplicated cervical/urethral/rectal: 250 mg IM single dose (must add antichlamydial coverage if Chlamydia not ruled out) 1, 2
• Disseminated gonococcal infection: 1 gram IM/IV every 24 hours, continue 24-48 hours after clinical improvement, then switch to oral therapy to complete 7 days 1
• Gonococcal conjunctivitis: 1 gram IM single dose with saline lavage 1
• Pharyngeal gonorrhea with elevated MICs: Consider 2 grams twice daily due to treatment failures with standard doses and variable pharyngeal tissue penetration 1

Skin and Soft Tissue Infections

• Standard dosing: 1 gram every 12-24 hours depending on severity 1, 2

Urinary Tract Infections (Pyelonephritis)

• Initial dose: 1 gram IV/IM, then transition to oral therapy 1

Pediatric Dosing Algorithm

Neonates (Critical Contraindications)

• DO NOT USE in hyperbilirubinemic neonates or premature infants 2
• DO NOT USE in neonates ≤28 days requiring calcium-containing IV solutions 2
• If used in neonates: 50 mg/kg/day every 24 hours, administered over 60 minutes to reduce bilirubin encephalopathy risk 5, 2

Infants and Children

• Meningitis: 100 mg/kg/day divided every 12 hours or once daily (maximum 4 grams daily) 5, 2
• Severe infections (pneumonia, sepsis): 50-100 mg/kg/day once daily or divided every 12 hours (maximum 4 grams daily) 5
• Less severe infections: 50-75 mg/kg/day once daily or divided every 12 hours (maximum 2 grams daily) 5, 2
• Acute otitis media: 50 mg/kg IM single dose (maximum 1 gram) 2
• Gonococcal infections (weight <45 kg): 125 mg IM single dose for uncomplicated; 50 mg/kg/day for 7 days for bacteremia/arthritis (10-14 days if meningitis) 5

Critical Administration Considerations

Calcium Interaction (Life-Threatening)

• Never mix with calcium-containing solutions (Ringer's, Hartmann's, parenteral nutrition) due to fatal precipitation risk 2
• In non-neonates, may give sequentially if lines thoroughly flushed between infusions 2
• Absolute contraindication in neonates receiving any calcium-containing IV solutions 2

Infusion Duration

• Adults: Administer IV over 30 minutes 2
• Neonates: Administer IV over 60 minutes to reduce bilirubin encephalopathy risk 2

Renal/Hepatic Impairment

• No dose adjustment required unless both severe renal AND hepatic impairment present 2
• Maximum 2 grams daily in elderly with combined organ dysfunction 2

Common Pitfalls to Avoid

1. Underdosing CNS infections: Using once-daily dosing for meningitis results in inadequate CSF concentrations during the dosing interval—always use 2 grams every 12 hours 1

2. Missing Listeria coverage: Ceftriaxone has NO activity against Listeria—always add ampicillin in patients ≥60 years with suspected meningitis 1

3. Forgetting antichlamydial coverage: Ceftriaxone has NO activity against Chlamydia trachomatis—must add azithromycin or doxycycline for gonococcal infections if chlamydia not excluded 2

4. Using in hyperbilirubinemic neonates: This can displace bilirubin from albumin binding sites, causing kernicterus—absolute contraindication 2

5. Calcium co-administration: Fatal precipitates can form—never give simultaneously, especially in neonates 2

6. Inadequate duration for streptococcal infections: Must continue for at least 10 days when treating Streptococcus pyogenes to prevent rheumatic fever 2

Evidence Quality Assessment

The strongest evidence comes from the FDA label 2 and recent CDC/IDSA guidelines compiled in Praxis Medical Insights 1, which uniformly recommend twice-daily dosing (2 grams every 12 hours) for CNS infections to ensure adequate CSF penetration throughout the dosing interval. The 2010 Surgical Infection Society/IDSA guidelines 3 provide robust support for intra-abdominal infection dosing. For pneumonia, a high-quality 2023 retrospective cohort study of nearly 4,000 patients 4 demonstrates non-inferiority of 1 gram daily in low-resistance settings, though this should not be extrapolated to CNS or endovascular infections where tissue penetration is critical.