What is the recommended treatment for typhoid fever?

Treatment of Typhoid Fever

Azithromycin 500 mg once daily for 7 days is the recommended first-line treatment for typhoid fever in adults, particularly given the high global rates of fluoroquinolone resistance. 1, 2, 3

First-Line Treatment Recommendations

Adults

• Azithromycin 500 mg orally once daily for 7 days is the preferred empiric therapy 2, 3
• This recommendation is based on superior efficacy with lower risk of clinical failure (OR 0.48) and shorter hospital stays compared to fluoroquinolones 3
• Azithromycin demonstrates a significantly lower risk of relapse (OR 0.09) compared to ceftriaxone 1, 3

Children

• Azithromycin 20 mg/kg/day (maximum 1g/day) orally for 7 days 1, 2
• This achieves a 94% cure rate in pediatric typhoid fever 1
• For severe cases requiring hospitalization: ceftriaxone 50-80 mg/kg/day (maximum 2g/day) IV for 5-7 days 1

Treatment Algorithm Based on Resistance Patterns

High Fluoroquinolone Resistance Areas (South Asia, Southeast Asia)

• Use azithromycin as first-line therapy 2, 3
• Over 70% of S. typhi isolates in many regions are now fluoroquinolone-resistant 1
• Do not use ciprofloxacin empirically for cases originating from South Asia due to high resistance rates 3, 4

Fully Susceptible Strains (Rare)

• Fluoroquinolones (ciprofloxacin or ofloxacin) may be used if susceptibility is confirmed 1, 5
• However, azithromycin remains a strong alternative even for susceptible strains 2

Severe Cases Requiring Parenteral Therapy

• Ceftriaxone 1-2g IV/IM daily for adults or 50-80 mg/kg/day for children (maximum 2g/day) for 5-7 days 2
• Transition to oral azithromycin once clinical improvement occurs and temperature has been normal for 24 hours 1, 2

Alternative Oral Options

Cefixime

• 8 mg/kg/day as a single daily dose for children (over 28 days old) 1
• 400 mg orally once daily for adults 1
• Treatment duration: 7-14 days 1
• Useful alternative when azithromycin is not available or tolerated

Clinical Management Essentials

Diagnostic Approach

• Obtain blood cultures before starting antibiotics whenever possible 1, 2
• Blood cultures have highest yield within the first week of symptom onset 2
• For patients with sepsis features, start broad-spectrum therapy immediately after culture collection 2, 3

Monitoring Treatment Response

• Expect fever clearance within 4-5 days of appropriate therapy 1, 2, 3
• If fever persists beyond 5 days, consider treatment failure or complications 1
• Monitor for gastrointestinal adverse effects with azithromycin (nausea, vomiting, abdominal pain, diarrhea) 2, 3

Duration of Therapy

• Complete 7 days of appropriate antibiotics for uncomplicated enteric fever 1
• Do not discontinue treatment prematurely to prevent relapse 2

Critical Complications to Monitor

• Complications occur in 10-15% of patients, more likely if illness duration exceeds 2 weeks 2
• Intestinal perforation requires immediate surgical intervention 2
• Simple excision and closure is reported in up to 88.2% of perforation cases 2

Common Pitfalls to Avoid

• Never rely on ciprofloxacin for empiric therapy in travelers from South Asia - resistance rates are prohibitively high 3, 4
• Do not use multivalent typhoid-paratyphoid vaccines - they are ineffective and increase reaction risk 6
• Do not assume vaccination provides complete protection - typhoid vaccines are not 100% effective and do not protect against paratyphoid 6, 2, 3
• Avoid premature discontinuation of antibiotics - complete the full course to prevent relapse 2
• Do not delay surgical consultation if intestinal perforation is suspected 2

Resistance Context

The treatment landscape has shifted dramatically due to antimicrobial resistance. While older guidelines recommended fluoroquinolones as first-line therapy 7, 8, current resistance patterns (particularly nalidixic acid resistance serving as a marker for decreased fluoroquinolone susceptibility) have made azithromycin the preferred empiric choice 1, 2, 3. Ciprofloxacin-resistant and even ceftriaxone-resistant typhoid is now common in Pakistan 4, emphasizing the importance of local resistance pattern awareness and culture-guided therapy when possible.