What is the recommended treatment regimen for a patient diagnosed with typhoid fever?

Treatment of Typhoid Fever

Azithromycin 500 mg once daily for 7 days is the preferred first-line treatment for adults with typhoid fever, particularly given that fluoroquinolone resistance now exceeds 70% in most endemic regions. 1, 2

First-Line Treatment Regimen

Adults:

• Azithromycin 500 mg orally once daily for 7 days 1, 2
• This regimen demonstrates superior outcomes with lower clinical failure rates (OR 0.48) compared to fluoroquinolones 1, 2
• Hospital stays are approximately 1 day shorter compared to fluoroquinolone therapy 1, 2

Children:

• Azithromycin 20 mg/kg/day (maximum 1g/day) orally once daily for 7 days 1, 2

When to Use IV Therapy

For severe cases or inability to tolerate oral medications:

• Adults: Ceftriaxone 1-2g IV/IM once daily for 5-7 days 1, 3
• Children: Ceftriaxone 50-80 mg/kg/day (maximum 2g/day) IV/IM once daily for 5-7 days 1, 3
• Ceftriaxone achieves fever clearance in a mean of 4 days and has demonstrated cure rates of 79-97% 3, 4, 5

Critical Diagnostic Steps Before Treatment

• Obtain blood cultures immediately before starting antibiotics—they have the highest diagnostic yield (40-80% sensitivity) within the first week of symptoms 6, 1, 7
• If the patient is clinically unstable or septic, start empiric treatment immediately after collecting cultures 1, 7
• Do not use the Widal test for diagnosis—it has poor specificity (68.44%) and very poor positive predictive value (5.7%) 7

Why Azithromycin Over Other Options

Fluoroquinolones (ciprofloxacin) should NOT be used empirically:

• Resistance exceeds 70% in South Asia and approaches 96% in some regions 6, 1, 2
• Only consider fluoroquinolones if susceptibility is confirmed AND the patient traveled from sub-Saharan Africa 6, 7

Cefixime should be avoided as first-line:

• Treatment failure rates of 4-37.6% have been documented 6, 1
• If cefixime must be used, mandatory test-of-cure at 1 week is required 1

Azithromycin advantages:

• Dramatically lower relapse risk (OR 0.09) compared to ceftriaxone 1, 2
• Relapse rates <3% when full course is completed 6, 1
• Once-daily dosing improves compliance 4

Expected Clinical Response and Monitoring

• Fever should clear within 4-5 days of appropriate antibiotic therapy 6, 1, 2, 7
• If no clinical improvement by day 5, consider antibiotic resistance or alternative diagnosis 6
• Blood cultures become negative earlier with ceftriaxone (0% positive on day 3) compared to chloramphenicol (60% positive on day 3) 5

Critical Pitfalls to Avoid

• Never discontinue antibiotics prematurely—complete the full 7-day course even if fever resolves early, as relapse occurs in 10-15% of inadequately treated cases 1, 2, 7
• Never use ciprofloxacin empirically for travel-associated cases from South or Southeast Asia—resistance is nearly universal 6, 1, 2, 7
• Never rely solely on Widal test for diagnosis—supplement with blood cultures 7

Adverse Effects to Monitor

Azithromycin:

• Common gastrointestinal symptoms: nausea, vomiting, abdominal pain, diarrhea 1, 2, 7
• Monitor for QT prolongation, especially with concurrent QT-prolonging medications 1, 2

Ceftriaxone:

• Reduced bone marrow suppression compared to chloramphenicol 5
• Generally well-tolerated with minimal serious adverse reactions 3

Complications Requiring Surgical Intervention

• Intestinal perforation occurs in 10-15% of patients when illness duration exceeds 2 weeks 6, 1, 2, 7
• Requires immediate surgical intervention with simple excision and closure (success rate up to 88.2%) 1, 2
• Other complications include gastrointestinal bleeding and typhoid encephalopathy 6, 7

Prevention for Future Exposure

Vaccination is recommended for:

• Travelers to endemic areas (Latin America, Asia, Africa) with moderate to high risk of exposure 6, 1, 2
• Household contacts of documented typhoid carriers 6
• Microbiology laboratory workers routinely exposed to S. typhi cultures 6

Vaccine options:

• Ty21a oral vaccine: One enteric-coated capsule on alternate days for total of 4 capsules, taken with cool liquid ≤37°C, 1 hour before meals; booster every 5 years 6, 1
• Parenteral inactivated vaccine: 0.5 mL subcutaneously in 2 doses separated by ≥4 weeks; booster every 3 years 6, 1

Important vaccination limitations:

• Provides only 50-80% protection 1, 2
• Does not protect against Salmonella Paratyphi 6, 1, 2
• Hand hygiene and food/water safety precautions remain essential and should not be replaced by vaccination alone 1, 2