Treatment of Enteric Fever
First-Line Antibiotic Selection
Azithromycin 20 mg/kg/day (maximum 1g/day) orally for 7 days is the preferred first-line treatment for uncomplicated enteric fever, particularly given the global rise in fluoroquinolone resistance. 1, 2
Why Azithromycin is Superior
Azithromycin demonstrates a 94% cure rate in children with typhoid fever and shows significantly lower risk of clinical failure (OR 0.48) compared to fluoroquinolones, especially in regions with multidrug-resistant (MDR) or nalidixic acid-resistant strains 1, 2, 3
Azithromycin reduces hospital stay by approximately 1 day (mean difference -1.04 days) compared to fluoroquinolones 2, 3
Relapse rates are dramatically lower with azithromycin (OR 0.09) compared to ceftriaxone 1, 2, 3
Over 70% of S. typhi isolates in many regions are now resistant to fluoroquinolones, making empiric fluoroquinolone use problematic 1
Severe Cases Requiring Hospitalization
For patients with severe enteric fever or sepsis, initiate ceftriaxone 50-80 mg/kg/day (maximum 2g/day) intravenously for 5-7 days immediately after obtaining blood cultures. 1, 2
Ceftriaxone shows faster fever clearance (0.52 days shorter) compared to azithromycin in some studies, though azithromycin has lower relapse rates 2
Switch to oral therapy once clinical improvement occurs and temperature has been normal for 24 hours 1
Special Population: Infants Under 3 Months
Treat infants under 3 months exclusively with ceftriaxone (third-generation cephalosporin) at 50-80 mg/kg/day IV, not azithromycin. 1, 2
Alternative Oral Option: Cefixime
Cefixime 8 mg/kg/day as a single daily dose for 7-14 days is an acceptable oral alternative, particularly in children over 28 days old 1
In a randomized trial, ofloxacin showed fewer treatment failures than cefixime, but this was before widespread fluoroquinolone resistance 1
Critical Diagnostic Steps Before Treatment
Always obtain blood cultures before initiating antibiotics whenever possible to confirm diagnosis and guide antimicrobial therapy 1, 2
For patients with clinical features of sepsis, initiate broad-spectrum antimicrobial therapy immediately after blood culture collection, then narrow therapy based on susceptibility results 1, 2
Also collect stool and urine cultures in suspected sepsis cases 1
Expected Clinical Response and Monitoring
Fever clearance should occur within 4-5 days of appropriate therapy 1
If fever persists beyond 5 days, consider treatment failure and reassess antibiotic choice based on susceptibility patterns 1
Monitor for dehydration, which increases risk of life-threatening complications, especially in young children and older adults 2
Common Pitfalls to Avoid
Do not use ciprofloxacin or other fluoroquinolones empirically for cases originating from South Asia due to resistance rates exceeding 90% in some areas 4, 1
Fluoroquinolone resistance is essentially a class effect, so switching between different fluoroquinolones will not overcome resistance 1
Do not rely solely on clinical presentation for diagnosis; blood cultures are essential 1, 2
Always modify therapy when susceptibility results become available rather than continuing empiric treatment 2
Supportive Care
Evaluate all patients for dehydration and provide isotonic intravenous fluids for severe dehydration 2
Reassess fluid and electrolyte balance in patients with persistent symptoms 1
Resistance Context
The recommendation for azithromycin as first-line therapy represents a shift from older guidelines that favored fluoroquinolones. This change is driven by:
Emergence of nalidixic acid and fluoroquinolone resistance in Salmonella from India and sub-Saharan Africa 4
Clinical trial data from Thailand showing azithromycin superiority over levofloxacin in settings with >90% fluoroquinolone-resistant Campylobacter (though this was for travelers' diarrhea, the resistance patterns parallel enteric fever) 4
Systematic reviews demonstrating azithromycin's lower clinical failure rates specifically in populations with drug-resistant strains 3, 5