What is the recommended intravenous treatment for typhoid fever in pediatric patients?

Intravenous Treatment of Typhoid Fever in Pediatrics

For pediatric patients requiring intravenous treatment of typhoid fever, ceftriaxone 50-80 mg/kg/day IV once daily for 5-7 days is the recommended first-line therapy, with azithromycin 20 mg/kg/day (maximum 1g/day) for 7 days as an equally effective alternative that can be transitioned to oral administration. 1, 2, 3

Treatment Algorithm Based on Clinical Severity and Local Resistance

First-Line IV Options

• Ceftriaxone 50-80 mg/kg/day IV once daily (maximum 2g/day) for 5-7 days is the preferred parenteral option for severe typhoid fever in children 1, 4
• Administer ceftriaxone over 60 minutes in neonates to reduce risk of bilirubin encephalopathy; 30 minutes is acceptable in older children 4
• Azithromycin 20 mg/kg/day IV (maximum 1g/day) for 7 days is equally effective and demonstrates superior outcomes in areas with high fluoroquinolone resistance 2, 3, 5

Why These Agents Are Preferred

• Azithromycin shows dramatically lower relapse rates (OR 0.09) compared to ceftriaxone, though both are effective for acute treatment 2, 6
• Ceftriaxone achieves faster fever clearance (mean 3.2-5.4 days) compared to oral alternatives 7, 8
• Both agents remain effective against multidrug-resistant strains that are resistant to chloramphenicol, ampicillin, and trimethoprim-sulfamethoxazole 7, 9

Specific Dosing Guidelines by Age and Weight

Neonates (≤28 days)

• Ceftriaxone is contraindicated in premature neonates and in any neonate requiring calcium-containing IV solutions due to risk of fatal ceftriaxone-calcium precipitation 4
• If ceftriaxone must be used in term neonates without calcium needs, administer over 60 minutes at 50 mg/kg/day once daily 4

Infants and Children

• Ceftriaxone: 50-80 mg/kg/day IV once daily (maximum 2g/day) for 5-7 days 1, 4
• Azithromycin: 20 mg/kg/day IV (maximum 1g/day) for 7 days, with transition to oral therapy when clinically improved 2, 3, 5
• For meningitis complicating typhoid (rare), increase ceftriaxone to 100 mg/kg/day (maximum 4g/day) 4

When to Use IV vs. Oral Therapy

• Initiate IV therapy for: severe illness, inability to tolerate oral medications, suspected complications (intestinal perforation, encephalopathy), or sepsis features 3, 6
• Transition to oral therapy when: fever resolves, patient tolerates oral intake, and clinical improvement is evident (typically 4-5 days) 2, 3
• Complete the full 7-day course even after transitioning to oral therapy to prevent relapse 2, 3

Expected Clinical Response and Monitoring

• Fever should clear within 4-5 days of appropriate therapy; if no improvement by day 5, consider resistance or alternative diagnosis 2, 3, 6
• Mean defervescence time with ceftriaxone is 3.2-5.4 days 7, 8
• Obtain blood cultures before initiating antibiotics whenever possible, as they have highest yield in the first week of symptoms 2, 6

Critical Pitfalls to Avoid

• Never use calcium-containing diluents (Ringer's solution, Hartmann's solution) with ceftriaxone due to risk of fatal precipitation 4
• Do not administer ceftriaxone simultaneously with calcium-containing IV solutions via Y-site; flush lines thoroughly between infusions in patients >28 days old 4
• Avoid ciprofloxacin empirically for cases from South/Southeast Asia where resistance exceeds 70-96% 2, 3, 6
• Do not use cefixime as first-line IV therapy; it has treatment failure rates of 4-37.6% and is inferior to both ceftriaxone and azithromycin 2
• Complete the full antibiotic course even if fever resolves early, as relapse occurs in 10-15% of inadequately treated cases 2, 3

Management of Complications

• Intestinal perforation occurs in 10-15% of patients with illness duration exceeding 2 weeks 2, 3
• Requires immediate surgical consultation for simple excision and closure, successful in up to 88.2% of cases 2
• Continue IV antibiotics throughout surgical management and recovery 2

Adverse Effects to Monitor

Ceftriaxone

• Monitor for hypersensitivity reactions, particularly in penicillin-allergic patients 4
• Watch for biliary sludging (reversible upon discontinuation) 4
• No dosage adjustment needed for renal or hepatic impairment unless severe 4

Azithromycin

• Common gastrointestinal symptoms: nausea, vomiting, abdominal pain, diarrhea 2, 3, 6
• Monitor for QT prolongation, especially with concurrent QT-prolonging medications 2, 3

Alternative Regimens for Specific Scenarios

• For confirmed fluoroquinolone-susceptible strains: Ciprofloxacin 15 mg/kg IV every 12 hours (maximum 30 mg/kg/day) for 7-10 days 1
• For multidrug-resistant strains in resource-limited settings: Ceftriaxone remains the most reliable option 7, 9
• Flexible-duration ceftriaxone protocol: 75 mg/kg/day IV until defervescence plus 5 additional days (typically 8-10 days total) is equally effective as 14-day courses 7

Transition to Oral Therapy

• Azithromycin: Continue at 20 mg/kg/day orally (maximum 1g/day) to complete 7-day course 2, 3
• Cefixime: 20 mg/kg/day orally divided every 12 hours for 7 days (only if susceptibility confirmed) 10, 9
• Oral therapy should begin only after clinical improvement and ability to tolerate oral intake 2, 3