In a child with ≥5 days fever, headache, abdominal pain, constipation or diarrhea and possible exposure to contaminated food or water, how should enteric fever be diagnosed and what is the appropriate treatment?

Diagnosis and Treatment of Enteric Fever in Children

Diagnosis

Blood culture is the essential diagnostic test and must be obtained before starting antibiotics in any child with ≥5 days of fever and possible enteric fever exposure. 1, 2

When to Suspect Enteric Fever

Suspect enteric fever in a febrile child (with or without diarrhea) who has: 1

• Travel history to endemic areas (South Asia, Southeast Asia, Central/South America, Africa) 1
• Consumed foods prepared by people with recent endemic exposure 1
• Laboratory exposure to Salmonella typhi or Paratyphi 1

Clinical Presentation in Children

The typical presentation includes: 3

• Gradual fever onset over 3-7 days with malaise, headache, and myalgia 3
• Gastrointestinal symptoms: abdominal pain (31%), diarrhea (37%), or constipation 4
• Feverish gastroenteritis is particularly common in children (61% of cases) 4
• Hepatosplenomegaly is the most common physical finding 5
• Abdominal tenderness is the second most common sign 5

Diagnostic Testing Algorithm

For children with clinical features of sepsis or severe illness: 1, 2

1. Obtain blood cultures immediately before starting antibiotics 1, 2
2. Obtain stool and urine cultures as well 1
3. Start broad-spectrum empiric antibiotics immediately after culture collection 1, 2

For infants <3 months with fever: 1

• Blood cultures are mandatory regardless of other symptoms 1

Important caveat: Blood culture sensitivity is suboptimal, so negative cultures do not rule out enteric fever if clinical suspicion remains high. 6

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Treatment

Azithromycin 20 mg/kg/day (maximum 1g/day) orally for 7 days is the preferred first-line therapy for mild to moderate enteric fever in children, particularly given high fluoroquinolone resistance rates. 2

Treatment Selection Based on Severity

For mild to moderate cases (outpatient): 2

• Azithromycin 20 mg/kg/day (maximum 1g/day) orally for 7 days 2
• Demonstrates 94% cure rate in children 2
• Lower risk of clinical failure (OR 0.48) compared to fluoroquinolones 2
• Lower risk of relapse (OR 0.09) compared to ceftriaxone 2

For severe cases or hospitalized patients: 2

• Ceftriaxone 50-80 mg/kg/day (maximum 2g/day) IV for 5-7 days 2
• Time to defervescence 0.52 days shorter than azithromycin 2
• Lower clinical failure rate compared to azithromycin in severe cases 2

For infants <3 months: 1, 2

• Third-generation cephalosporin (ceftriaxone) is mandatory first-line 1, 2
• Dose: 50-80 mg/kg/day IV 2

For children with neurologic involvement: 1

• Use third-generation cephalosporin regardless of age 1

Critical Treatment Principles

Narrow therapy when susceptibility results become available: 1, 2

• Initial broad-spectrum coverage should be tailored based on culture and sensitivity 1
• If isolate unavailable, tailor to susceptibility patterns from the acquisition setting 1

Expected clinical response: 2

• Fever should clear within 4-5 days of appropriate therapy 2
• If no improvement by day 5, reassess diagnosis and consider complications 2

Supportive Care

Evaluate and treat dehydration aggressively: 2

• Dehydration increases risk of life-threatening complications, especially in young children 2
• Use isotonic IV fluids for severe dehydration 2

Common Pitfalls to Avoid

Do NOT use fluoroquinolones empirically for children with travel from South Asia: 2, 7

• High fluoroquinolone resistance rates in this region 2, 7
• Pakistan has ongoing XDR (extensively drug-resistant) enteric fever outbreak 7

Do NOT delay antibiotics in septic-appearing children: 1

• Obtain cultures first, but start empiric therapy immediately 1
• Untreated illness can lead to life-threatening complications in the second week 3

Do NOT assume negative blood cultures rule out enteric fever: 6

• Blood culture sensitivity is low 6
• Clinical suspicion and epidemiologic factors should guide treatment decisions 6

Monitoring for Complications

Watch for complications that occur in approximately 33% of cases: 4, 5

• Thrombocytopenia (most common, 13% of cases) 5
• Intestinal perforation (3%) 5
• Rectal bleeding (3%) 5
• Ascites or pleural effusion (4%) 5
• Meningitis (1%) 5

Complications are more common in children ≥5 years of age. 5