What is the recommended antimicrobial regimen and supportive care for enteric fever (typhoid and paratyphoid)?

Recommended Treatment for Enteric Fever (Typhoid and Paratyphoid)

For clinically unstable patients with suspected enteric fever, start ceftriaxone 50-80 mg/kg/day (maximum 2g/day) IV immediately after obtaining blood cultures, then switch to azithromycin 20 mg/kg/day (maximum 1g/day) orally for 7 days once clinically stable and susceptibility results confirm sensitivity. 1, 2

Initial Assessment and Culture Collection

• Always obtain blood cultures before starting antibiotics when the patient's condition permits, as blood culture remains the gold standard with highest yield in the first week of symptoms 3
• Collect stool and urine cultures in addition to blood cultures when sepsis is suspected 2
• Do not delay empiric antibiotics in patients with clinical features of sepsis, documented fever ≥38.5°C in travelers from endemic areas, or signs of septic shock 1, 3

Empiric Antimicrobial Therapy

For Severe/Hospitalized Cases:

• Ceftriaxone 50-80 mg/kg/day (maximum 2g/day) IV for 5-7 days is the preferred initial therapy for severe cases requiring hospitalization 2, 4
• Ceftriaxone reduces treatment failure risk compared to fluoroquinolones (HR 0.24,95% CI 0.08-0.73) 2
• Switch to oral therapy once fever has been normal for 24 hours and clinical improvement occurs 2

For Mild-Moderate Uncomplicated Cases:

• Azithromycin 20 mg/kg/day (maximum 1g/day) orally for 7 days is now the preferred first-line agent per WHO 2024 guidelines 2
• Azithromycin achieves 94% cure rate and significantly reduces clinical failure compared to fluoroquinolones (OR 0.48,95% CI 0.26-0.89) 2, 5
• Azithromycin shortens hospital stay by approximately 1 day compared to fluoroquinolones 5
• Azithromycin markedly lowers relapse risk compared to ceftriaxone (OR 0.09,95% CI 0.01-0.70) 2, 5

Alternative Oral Therapy:

• Cefixime 8 mg/kg/day (maximum 400mg) as a single daily dose for 7-14 days can be used as an oral alternative, particularly in children over 28 days old 2
• However, cefixime may have higher clinical failure rates compared to fluoroquinolones (RR 13.39,95% CI 3.24-55.39) 4

Geographic and Resistance Considerations

South and Southeast Asia (High Fluoroquinolone Resistance):

• Avoid ciprofloxacin empirically as >70% of S. typhi isolates are now resistant to fluoroquinolones in these regions 2, 6
• Use azithromycin or ceftriaxone as first-line therapy 1, 2

Sub-Saharan Africa (Lower Fluoroquinolone Resistance):

• Ciprofloxacin 500-750mg twice daily for 7-14 days remains an alternative if susceptibility is confirmed 1, 7
• However, azithromycin is still preferred given global resistance trends 2

When Susceptibility Results Are Available:

• Switch to ciprofloxacin only if the isolate is fully susceptible (not just nalidixic acid-susceptible, as this indicates reduced fluoroquinolone susceptibility) 1, 2
• Fluoroquinolone resistance is a class effect, so avoid all fluoroquinolones if any resistance is detected 2

Special Populations

Infants Under 3 Months:

• Use third-generation cephalosporin (ceftriaxone) as first-line therapy 1, 2

Children with Neurologic Involvement:

• Use third-generation cephalosporin (ceftriaxone) rather than azithromycin 1

Immunocompromised Patients:

• Initiate broad-spectrum therapy immediately with ceftriaxone, then narrow based on susceptibility 1

Treatment Duration and Monitoring

• Total treatment duration is 7 days for uncomplicated cases with appropriate antibiotics 2
• Severe cases may require 10-14 days depending on clinical response 2
• Expected fever clearance within 4-5 days of appropriate therapy 2
• If fever persists beyond 5 days, consider treatment failure and reassess for complications or resistance 2

Supportive Care

• Aggressive fluid and electrolyte repletion is essential, as primary therapy with antibiotics serving as adjunctive treatment 1
• Monitor for complications including intestinal perforation (typically third week if untreated), gastrointestinal bleeding, and encephalopathy 3
• Watch for signs of perforation: severe abdominal pain, peritoneal signs, or sudden clinical deterioration 3

Critical Pitfalls to Avoid

• Do not use fluoroquinolones empirically for infections acquired from South/Southeast Asia due to >70% resistance rates 2, 6
• Do not use chloramphenicol, ampicillin, or co-trimoxazole empirically due to widespread multidrug resistance 2
• Do not delay antibiotics in septic patients while waiting for culture results 1, 3
• Do not assume nalidixic acid susceptibility means full fluoroquinolone susceptibility—this indicates reduced susceptibility and predicts clinical failure 2, 4
• Do not treat asymptomatic contacts empirically, but advise appropriate infection control measures 1

Obsolete Treatments

• Chloramphenicol, ampicillin, and co-trimoxazole should only be considered as last-resort options when no other antibiotics are available due to widespread resistance 2, 8