What is the treatment for a child with typhoid fever?

Treatment of Typhoid Fever in Children

Azithromycin 20 mg/kg/day (maximum 1g/day) orally for 7 days is the preferred first-line treatment for typhoid fever in children, given widespread fluoroquinolone resistance exceeding 70% in most endemic regions. 1

First-Line Antibiotic Therapy

• Azithromycin achieves a 94% cure rate in children with significantly lower clinical failure risk (OR 0.48) compared to fluoroquinolones and dramatically reduces relapse rates (OR 0.09) compared to ceftriaxone. 1

• The American Academy of Pediatrics recommends this regimen as the preferred first-line treatment, particularly because fluoroquinolone resistance now exceeds 70% in most endemic regions, reaching up to 96% in some South Asian areas. 1

• Azithromycin demonstrates zero relapses in pediatric studies versus 4-6 relapses documented in ceftriaxone groups, making it superior for preventing recurrent disease. 1

Alternative Treatment Options for Specific Situations

Severe Cases Requiring Hospitalization

• For severe typhoid requiring hospitalization, the Infectious Diseases Society of America recommends ceftriaxone 50-80 mg/kg/day (maximum 2g/day) IV/IM for 5-7 days. 1

• Third-generation cephalosporins such as ceftriaxone are currently recommended as first-line therapy for severe cases, particularly given increasing multi-drug resistance patterns. 2

Infants Under 3 Months

• For infants under 3 months, the American Academy of Pediatrics recommends third-generation cephalosporin (ceftriaxone) due to age-specific considerations. 1

• Neonatal typhoid fever is rare but often life-threatening, with vertical intrauterine transmission from a typhoid-infected mother being the primary route. 3

• Where typhoid is endemic, S. typhi should be considered as a cause of sepsis neonatorum and appropriate antibiotics included in empiric therapy. 3

Diagnostic Approach Before Treatment

• The CDC recommends obtaining 2-3 blood cultures before initiating antibiotics to maximize detection given low-magnitude bacteremia. 1

• Blood cultures have the highest yield within the first week of symptom onset. 1

• Diagnosis requires isolation of Salmonella typhi from blood, bone marrow, or bile, while S. typhi found in stool or urine may reflect chronic asymptomatic carriage rather than acute disease. 4

Monitoring Treatment Response

• Fever should clear within 4-5 days of appropriate therapy according to WHO guidelines. 1

• If no clinical response occurs by day 5, consider antibiotic resistance or an alternative diagnosis. 1

• Most patients respond well to appropriate antimicrobial therapies when treatment is initiated promptly. 5

Essential Supportive Care

Hydration Management

• The American Academy of Pediatrics recommends ensuring adequate hydration with oral rehydration solution or IV fluids, as dehydration increases the risk of life-threatening complications, especially in infants. 1

• For mild-moderate dehydration, use oral rehydration solution with 50-90 mEq/L sodium: 50 mL/kg over 2-4 hours for mild dehydration and 100 mL/kg over 2-4 hours for moderate dehydration. 6

• For severe dehydration, immediate IV rehydration with Ringer's lactate or normal saline is necessary, with boluses of 20 mL/kg until pulse, perfusion, and mental status normalize. 6

Nutritional Support

• Continue breastfeeding throughout illness if the infant is breastfed. 1

• Breast-fed infants should continue nursing on demand, while formula-fed infants should receive full-strength lactose-free or lactose-reduced formulas immediately upon rehydration. 6

• Older children should receive an age-appropriate usual diet, with starches, cereals, yogurt, fruits, and vegetables recommended. 7

• Replace ongoing losses with 10 mL/kg ORS for each watery stool and 2 mL/kg for each vomiting episode. 6

Geographic Resistance Considerations

• The WHO recommends considering local resistance patterns when selecting empiric therapy, as these vary geographically and change over time. 1

• South Asia has >70% fluoroquinolone resistance, up to 96% in some areas, making fluoroquinolones inappropriate for empiric therapy in children from these regions. 1

• If sensitive to quinolones based on culture results, fluoroquinolones such as ciprofloxacin may be administered, but this should not be assumed empirically. 2

Common Pitfalls to Avoid

• Do not use fluoroquinolones empirically given widespread resistance exceeding 70% in endemic regions, despite their historical use as first-line agents. 1

• Avoid antimotility agents in children with typhoid fever due to the risk of toxic megacolon and worsening of systemic disease. 6

• Do not rely solely on stool cultures, as S. typhi in stool may reflect chronic carriage rather than acute infection; blood cultures are essential. 4

Hospital Admission Criteria

• Admit children with severe dehydration, failed oral rehydration therapy, altered mental status, signs of sepsis, or those under 3 months with suspected bacterial infection. 6

• Thrombocytopenia (occurring in 13% of cases), intestinal perforation (3%), rectal bleeding (3%), ascites or pleural effusion (4%), and meningitis (1%) are complications requiring hospitalization. 5

• The incidence of complications tends to be higher among children 5 years of age or older. 5