What are the recommended ceftriaxone injection doses for prophylaxis and for treatment according to the Infectious Diseases Society of America (IDSA) guidelines?

Ceftriaxone Dosing for Prophylaxis and Treatment per IDSA Guidelines

For prophylaxis in neonates born to mothers with untreated gonorrhea, administer ceftriaxone 25-50 mg/kg IV or IM (not to exceed 125 mg) as a single dose; for treatment of most adult infections, use 1-2 grams IV/IM every 24 hours, with specific dosing of 2 grams every 12 hours reserved for CNS infections including meningitis. 1, 2

Prophylaxis Dosing

Neonatal Gonococcal Prophylaxis

• Infants born to mothers with untreated gonorrhea receive ceftriaxone 25-50 mg/kg IV or IM as a single dose, not to exceed 125 mg total. 1
• This prophylactic regimen is indicated only when the mother has documented untreated gonococcal infection and the infant shows no signs of active infection. 1
• Ceftriaxone should be administered cautiously in infants with elevated bilirubin levels, particularly premature infants, due to risk of kernicterus from bilirubin displacement. 1

Surgical Prophylaxis

• A single dose of ceftriaxone is as effective as multiple doses of cefazolin for perioperative prophylaxis. 3
• The convenience of once-daily dosing makes ceftriaxone advantageous for surgical prophylaxis compared to antibiotics requiring more frequent administration. 4

Treatment Dosing by Infection Type

Uncomplicated Gonococcal Infections (Adults)

• Administer ceftriaxone 250 mg IM as a single dose for uncomplicated cervical, urethral, rectal, or pharyngeal gonorrhea. 2, 5
• Always add treatment for Chlamydia trachomatis if chlamydial infection has not been excluded, as co-infection occurs in approximately 50% of cases. 2, 6
• The 250 mg dose achieves cure rates of 98% for uncomplicated infections at all anatomic sites. 5, 7

Disseminated Gonococcal Infection (DGI)

• Begin with ceftriaxone 1 gram IM or IV every 24 hours, continuing for 24-48 hours after clinical improvement begins, then switch to oral therapy to complete one full week of treatment. 2
• This stepdown approach balances efficacy with cost-effectiveness and patient convenience. 2

Gonococcal Meningitis and Endocarditis

• For gonococcal meningitis, administer ceftriaxone 1-2 grams IV every 12 hours for 10-14 days. 2
• For gonococcal endocarditis, use ceftriaxone 1-2 grams IV every 12 hours for at least 4 weeks. 2
• The twice-daily dosing for CNS infections ensures sustained therapeutic CSF concentrations throughout the dosing interval. 2

Bacterial Meningitis (Empirical Treatment)

Algorithm for Empirical Meningitis Treatment:

1. For adults <60 years old: Ceftriaxone 2 grams IV every 12 hours 2
2. For adults ≥60 years old: Ceftriaxone 2 grams IV every 12 hours PLUS amoxicillin 2 grams IV every 4 hours (to cover Listeria monocytogenes) 2
3. If penicillin-resistant pneumococci suspected: Add vancomycin 15-20 mg/kg IV every 8-12 hours OR rifampicin 600 mg twice daily 2

Pathogen-Specific Duration:

• Meningococcal meningitis: 5 days (can discontinue if clinically recovered by day 5) 2
• Pneumococcal meningitis: 10-14 days (longer duration if delayed clinical response) 2
• Listeria monocytogenes: 21 days 2
• Haemophilus influenzae: 10 days 2
• Enterobacteriaceae: 21 days 2

Lyme Disease

• For Lyme disease with neurologic involvement or Lyme arthritis refractory to oral therapy, administer ceftriaxone 2 grams IV once daily for 2-4 weeks. 1, 2
• Studies demonstrate that 2-week and 4-week courses have similar efficacy (76% vs 70% cure rates), making 2 weeks the preferred duration for most patients. 1
• Oral antibiotics are preferred for initial treatment of Lyme arthritis without neurologic involvement, as intravenous therapy is more expensive and carries higher complication risk without improved outcomes. 1

Neonatal Infections (Treatment)

For neonatal disseminated gonococcal infection (sepsis, arthritis, meningitis):

• Ceftriaxone 25-50 mg/kg/day IV or IM as a single daily dose for 7 days 1
• Extend duration to 10-14 days if meningitis is documented 1
• Alternative: Cefotaxime 25 mg/kg IV or IM every 12 hours with same duration parameters 1

Endocarditis (Non-Gonococcal)

For HACEK organisms:

• Ceftriaxone 2 grams IV/IM once daily for 4 weeks (native valve) or 6 weeks (prosthetic valve) 2

For highly penicillin-susceptible viridans group streptococci (MIC ≤0.12 μg/mL):

• Monotherapy: Ceftriaxone 2 grams IV/IM once daily for 4 weeks 2
• Combination therapy: Ceftriaxone 2 grams IV/IM once daily for 2 weeks PLUS gentamicin 3 mg/kg daily for 2 weeks (not for patients with cardiac/extracardiac abscess, creatinine clearance <20 mL/min, or eighth cranial nerve dysfunction) 2

Critical Dosing Considerations and Pitfalls

When Twice-Daily Dosing is Essential

• CNS infections (meningitis, epidural abscess, subdural empyema) require 2 grams every 12 hours, especially during the first 24 hours, to achieve rapid CSF sterilization. 2
• Once-daily dosing may be considered for stable patients after the initial 24 hours, but this is not standard practice for meningitis. 2

Resistance Considerations

• For pharyngeal gonorrhea with elevated MICs or suspected ceftriaxone resistance, treatment failures have occurred with 250-500 mg doses; consider higher doses or twice-daily dosing of 2 grams. 2
• Pharyngeal infections are more difficult to eradicate due to variable pharmacokinetics in tonsillar tissue and high protein binding. 2
• If ceftriaxone treatment failure occurs, perform culture and susceptibility testing immediately and report to local health department within 24 hours. 2

Administration Routes

• IM and IV routes are interchangeable for most indications, though IM injection is painful and should be injected deep into large muscle mass. 2
• For single-dose regimens (gonorrhea prophylaxis, uncomplicated gonorrhea), IM administration is standard. 2, 5
• For meningitis and serious infections requiring twice-daily dosing, IV administration is preferred. 2

Pediatric Dosing Caps

• Pediatric weight-based dosing should not exceed adult dosing even when calculations suggest higher doses. 2
• Children weighing ≥45 kg should receive adult dosing regimens. 2

Common Adverse Effects

• Rash, fever, diarrhea, neutropenia, liver function abnormalities, and gallbladder "sludging" are common adverse effects. 2
• Neonatal hyperbilirubinemia risk requires caution in premature infants. 1

Outpatient Parenteral Antibiotic Therapy (OPAT)

• For stable patients with meningitis who are afebrile and clinically improving after 5 days of inpatient therapy, ceftriaxone 2 grams twice daily IV initially, with option to use 4 grams once daily IV after the first 24 hours. 2
• OPAT requires reliable IV access and 24-hour access to medical advice from the OPAT team. 2
• Once-daily dosing reduces overall healthcare costs without compromising efficacy when clinically appropriate. 2