What is the recommended dose and potential side effects of Ceftriaxone (a cephalosporin antibiotic) in pediatric patients, and are there any significant drug interactions?

Ceftriaxone Pediatric Dosing, Side Effects, and Drug Interactions

Recommended Dosing by Age and Weight

For most pediatric infections, ceftriaxone should be dosed at 50-75 mg/kg/day given once daily or divided every 12-24 hours, with a maximum daily dose of 4 grams. 1, 2

Neonatal Dosing (Age-Specific)

• Postnatal age ≤7 days: 50 mg/kg/day given every 24 hours 1, 2
• Postnatal age >7 days and weight ≤2000 g: 50 mg/kg/day given every 24 hours 1, 2
• Postnatal age >7 days and weight >2000 g: 50-75 mg/kg/day given every 24 hours 1, 2

Infants and Children (Beyond Neonatal Period)

• Standard infections: 50-75 mg/kg/day given once daily or divided every 12-24 hours 1, 2
• Severe infections (pneumonia, sepsis): 50-100 mg/kg/day given once daily or divided every 12-24 hours 2, 3
• Bacterial meningitis: 100 mg/kg/day divided every 12-24 hours (maximum 4 g daily) 2
• Penicillin-resistant pneumococcal infections: 100 mg/kg/day every 12-24 hours 2, 3

Maximum Dose Considerations

• Pediatric doses should never exceed adult doses (maximum 4 g daily) 2
• For severe sepsis, use the higher dosing range (80-100 mg/kg/day) rather than the lower end 2

Side Effects and Adverse Reactions

Common Side Effects

• Gastrointestinal disturbances: Diarrhea is a common problem that usually resolves when the antibiotic is discontinued 4
• Candida overgrowth: Sterilization of the gut with Candida albicans overgrowth occurred in 35% of neonates and infants 5
• Prolonged fever: Occurred in 13% of patients in clinical studies 5
• Pain at injection site: Intramuscular injection is painful and patients should be counseled accordingly 2

Serious Adverse Effects

• Neurological complications: Encephalopathy (disturbance of consciousness including somnolence, lethargy, and confusion), seizures, myoclonus, and nonconvulsive status epilepticus have been reported 4
• Hematologic effects: Neutropenia and leukopenia can develop, occasionally requiring discontinuation of therapy 6
• Positive Coombs' test: May occur during treatment 4

Critical Contraindication

Ceftriaxone should NEVER be used in hyperbilirubinemic neonates, especially prematures, as it can displace bilirubin from serum albumin. 1, 2, 4

Drug Interactions

Calcium-Containing Products

• Ceftriaxone-calcium precipitation: In vitro studies show that ceftriaxone recovery from plasma is reduced with calcium concentrations of 6 mM (24 mg/dL) or higher in adult plasma or 4 mM (16 mg/dL) or higher in neonatal plasma, reflecting potential ceftriaxone-calcium precipitation 4
• This interaction is particularly important in neonates receiving intravenous calcium-containing solutions 4

Probenecid

• The elimination of ceftriaxone is NOT altered when co-administered with probenecid, unlike other cephalosporins 4

Diagnostic Test Interference

• False-positive glucose readings: Nonenzymatic methods for urine glucose determination may give false-positive results; use enzymatic methods during ceftriaxone therapy 4
• Blood glucose monitoring systems: Ceftriaxone may falsely lower estimated blood glucose values with some monitoring systems 4
• Galactosemia testing: May result in positive test results for galactosemia 4

Special Populations and Considerations

Renal and Hepatic Impairment

• Dosage adjustments are NOT necessary for pediatric patients with renal or hepatic impairment when using dosages up to 2 grams per day 4
• Ceftriaxone is not significantly removed by hemodialysis 4

Pregnancy and Lactation

• Low concentrations are excreted in human milk; caution should be exercised when administered to nursing women 4

Clinical Efficacy Data

• Overall clinical cure rates of 94-97% have been demonstrated in pediatric patients with serious bacterial infections 7, 8
• Bacteriologic cure rates of 97-100% have been achieved 7, 5, 6

Common Pitfalls to Avoid

• Do not underdose severe sepsis: Use 80-100 mg/kg/day for severe sepsis, not the lower 50 mg/kg/day range 2
• Do not use in hyperbilirubinemic neonates: This is an absolute contraindication due to bilirubin displacement 1, 2, 4
• Do not mix with calcium-containing solutions: Particularly critical in neonates 4
• Monitor for neurological symptoms: Immediately discontinue if encephalopathy, seizures, or myoclonus develop 4