What are the indications, dosing regimens, contraindications, and major adverse effects of Rocephin (ceftriaxone) for adults and children?

Rocephin (Ceftriaxone): Comprehensive Clinical Guide

Indications

Ceftriaxone is indicated for serious bacterial infections caused by susceptible organisms, with particular strength against Streptococcus pneumoniae, Haemophilus influenzae, Neisseria species, and many Enterobacteriaceae. 1, 2

Primary Indications by System:

Central Nervous System:

• Bacterial meningitis (pneumococcal, meningococcal, H. influenzae, gram-negative enteric bacilli) 3, 1
• Epidural abscess and subdural empyema 2

Respiratory:

• Community-acquired pneumonia, including penicillin-resistant pneumococcal disease 3, 1, 4
• Severe pneumonia requiring hospitalization 1, 5

Intra-abdominal:

• Complicated intra-abdominal infections (appendicitis, peritonitis, diverticulitis) when combined with metronidazole 3
• Biliary tract infections 3

Genitourinary:

• Acute pyelonephritis 1, 2
• Gonococcal infections (uncomplicated and disseminated) 2

Cardiovascular:

• Infective endocarditis (viridans streptococci, HACEK organisms) 3, 2

Other:

• Skin and soft tissue infections 6, 4
• Bone and joint infections 7, 4
• Bacteremia/septicemia 1, 8
• Surgical prophylaxis (single-dose) 3, 8

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Dosing Regimens

Adult Dosing

Standard Infections:

• 1-2 grams IV/IM once daily for most infections 2, 4
• Skin/soft tissue: 1 gram every 12-24 hours depending on severity 2

Central Nervous System Infections:

• Bacterial meningitis: 2 grams IV every 12 hours (total 4 grams daily) for 10-14 days 3, 2
• Meningococcal meningitis: 2 grams IV every 12 hours for 5 days 2
• Gonococcal meningitis: 1-2 grams IV every 12 hours for 10-14 days 2

Endocarditis:

• Highly penicillin-susceptible viridans streptococci (MIC ≤0.12 μg/mL): 2 grams IV/IM once daily for 4 weeks (native valve) or 6 weeks (prosthetic valve) 2
• HACEK organisms: 2 grams IV/IM once daily for 4 weeks (native valve) or 6 weeks (prosthetic valve) 2

Gonococcal Infections:

• Uncomplicated (cervical, urethral, rectal): 250 mg IM single dose (must add azithromycin for chlamydia coverage) 2
• Disseminated gonococcal infection: 1 gram IM/IV every 24 hours, continue 24-48 hours after improvement, then switch to oral therapy to complete 7 days 2
• Gonococcal conjunctivitis: 1 gram IM single dose 2

Intra-abdominal Infections:

• Mild-to-moderate community-acquired: Ceftriaxone 1-2 grams daily + metronidazole 500 mg every 8 hours 3

Pediatric Dosing

Neonates:

• Age ≤7 days: 50 mg/kg/day IV/IM every 24 hours 1
• Age >7 days and ≤2000 g: 50 mg/kg/day every 24 hours 1
• Age >7 days and >2000 g: 50-75 mg/kg/day every 24 hours 1
• CONTRAINDICATED in hyperbilirubinemic neonates 1, 2

Infants and Children (Beyond Neonatal Period):

• Standard infections: 50-75 mg/kg/day once daily or divided every 12-24 hours (maximum 2 grams daily for non-meningeal infections) 1
• Bacterial meningitis: 100 mg/kg/day divided every 12-24 hours (maximum 4 grams daily) 1
• Severe infections/pneumonia: 50-100 mg/kg/day 1
• Penicillin-resistant pneumococcal pneumonia: 100 mg/kg/day every 12-24 hours 1

Gonococcal Infections (Pediatric):

• Children <45 kg, uncomplicated: 125 mg IM single dose 1, 2
• Children ≥45 kg: use adult dosing 2
• Bacteremia/arthritis: 50 mg/kg/day (maximum 1 gram) for 7 days 1, 2
• Meningitis: 50 mg/kg/day (maximum 2 grams) for 10-14 days 2

Endocarditis Prophylaxis (Dental Procedures):

• Adults: 1 gram IM/IV single dose 30-60 minutes before procedure 3
• Children: 50 mg/kg IM/IV single dose (maximum 1 gram) 3

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Contraindications

Absolute Contraindications:

Hyperbilirubinemic neonates, especially premature infants: Ceftriaxone can displace bilirubin from albumin binding sites, causing kernicterus and bilirubin encephalopathy. 1, 2

History of severe hypersensitivity (anaphylaxis, angioedema, urticaria) to ceftriaxone or other cephalosporins. 3

Concomitant administration with calcium-containing IV solutions in neonates: Risk of fatal ceftriaxone-calcium precipitates in lungs and kidneys. 2

Relative Contraindications:

History of anaphylaxis to penicillins: Cephalosporins should not be used in patients with history of anaphylaxis, angioedema, or urticaria with penicillins due to cross-reactivity risk (approximately 1-3%). 3

Severe renal and hepatic dysfunction combined: Dosage adjustment necessary only when both organ systems are impaired. 8

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Major Adverse Effects

Common (>1%):

Gastrointestinal:

• Diarrhea (most common) 2, 4
• Nausea and vomiting 4

Dermatologic:

• Rash 2, 4
• Candidiasis 4

Hematologic:

• Neutropenia 2
• Eosinophilia 4

Hepatic:

• Transient elevation of liver enzymes (AST, ALT) 2, 4

Local:

• Injection site pain (IM administration is notably painful) 1, 2
• Phlebitis (IV administration) 4

Serious but Less Common (<1%):

Biliary:

• Reversible biliary pseudolithiasis ("sludging"), particularly at doses ≥2 grams/day; incidence of true lithiasis <0.1% 2, 4

Hematologic:

• Thrombocytopenia 4
• Prolonged prothrombin time (rare; hypoprothrombinemic bleeding is NOT part of the adverse reaction profile) 8

Hypersensitivity:

• Anaphylaxis (rare) 4
• Stevens-Johnson syndrome (rare) 4

Renal:

• Ceftriaxone-calcium precipitates in neonates (potentially fatal) 2

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Critical Clinical Considerations

Dosing Frequency for CNS Infections:

For bacterial meningitis and other CNS infections, twice-daily dosing (2 grams every 12 hours) is essential for the first 24-48 hours to achieve rapid CSF sterilization and maintain therapeutic concentrations throughout the dosing interval. 2 Once-daily dosing may be considered for stable patients after initial improvement. 2

Resistance Considerations:

For pharyngeal gonorrhea with elevated MICs or suspected ceftriaxone resistance, treatment failures have been documented with standard 250-500 mg doses; higher doses (up to 2 grams twice daily) may be required. 2 Culture and susceptibility testing should be performed for treatment failures. 2

For penicillin-resistant pneumococcal meningitis, add vancomycin 15-20 mg/kg IV every 8-12 hours (targeting trough 15-20 mg/mL) or rifampin 600 mg twice daily to ceftriaxone. 2

Special Populations:

Patients ≥60 years with suspected meningitis require addition of ampicillin 2 grams IV every 4 hours to cover Listeria monocytogenes. 3, 2

Neonatal prophylaxis for gonococcal ophthalmia: 25-50 mg/kg (maximum 125 mg) IV/IM single dose for infants born to mothers with untreated gonorrhea. 2

Administration:

IM injection is painful; patients should be counseled accordingly and injection should be deep into large muscle mass. 1, 2 IV and IM routes are interchangeable for most indications. 2

Treatment Duration:

Meningococcal meningitis can be safely discontinued after 5 days if clinically recovered; pneumococcal meningitis requires 10-14 days. 2 Endocarditis requires minimum 4 weeks (native valve) or 6 weeks (prosthetic valve). 2

Cost and Convenience:

The long half-life (6-8 hours) permits once-daily dosing for most infections, facilitating outpatient parenteral antibiotic therapy (OPAT) and reducing healthcare costs without compromising efficacy. 8, 4, 5