What are the recommended empirical antibiotics for typhoid fever in India?

Empirical Antibiotics for Typhoid in India

Azithromycin 500 mg once daily for 7 days is the recommended first-line empirical antibiotic for typhoid fever in India due to widespread fluoroquinolone resistance exceeding 70% in South Asian isolates. 1, 2

Treatment Algorithm

First-Line Empirical Therapy

• Start azithromycin immediately for suspected typhoid fever in India, given fluoroquinolone resistance rates approaching 96% in some regions 1
• Adult dosing: 500 mg orally once daily for 7 days 1
• Pediatric dosing: 20 mg/kg/day (maximum 1g/day) orally for 7 days 2, 3
• Azithromycin demonstrates superior outcomes with lower clinical failure rates (OR 0.48) and significantly reduced relapse risk (OR 0.09) compared to other agents 1, 2

Severe Cases Requiring Hospitalization

• Use ceftriaxone for severe presentations with sepsis features or inability to tolerate oral therapy 2, 3
• Adult dosing: 1-2g IV/IM daily for 5-7 days 1
• Pediatric dosing: 50-80 mg/kg/day (maximum 2g/day) IV/IM for 5-7 days 2, 3
• Transition to oral azithromycin once afebrile for 24 hours and clinically improved 2

Alternative Oral Option

• Cefixime 8 mg/kg/day as single daily dose for 7-14 days can be used for uncomplicated cases when azithromycin is unavailable 3
• Adult dosing: 400 mg orally once daily 3

Critical Diagnostic Steps Before Treatment

• Obtain blood cultures immediately before starting antibiotics whenever possible, as they have the highest yield within the first week of symptom onset 1, 2
• For patients with sepsis features (fever ≥38.5°C, confusion, hypotension), start broad-spectrum therapy immediately after collecting blood, stool, and urine cultures 4, 3

Why Fluoroquinolones Should Be Avoided

• Never use ciprofloxacin or ofloxacin empirically for cases originating from India or South Asia 1, 2, 3
• Over 70% of S. typhi isolates in India are now fluoroquinolone-resistant, with resistance rates reaching 96% in some regions 1, 5
• Nalidixic acid-resistant S. typhi (NARST) infections are associated with longer fever duration, higher complication rates, and clinical failure of fluoroquinolone therapy 6
• Fluoroquinolones may only be considered if susceptibility is confirmed by culture, which takes several days 1

Expected Clinical Response and Monitoring

• Expect fever clearance within 4-5 days of appropriate azithromycin therapy 1, 2
• If no clinical improvement by day 5, consider antibiotic resistance or alternative diagnosis 1
• Monitor for complications (gastrointestinal bleeding, intestinal perforation, encephalopathy) which occur in 10-15% of patients, particularly after 2 weeks of illness 2, 1

Common Pitfalls to Avoid

• Do not discontinue antibiotics early even if fever resolves; complete the full 7-day course to prevent relapse, which occurs in 10-15% of inadequately treated cases 1
• Do not rely on clinical presentation alone for diagnosis; blood cultures are essential as they guide definitive therapy 2, 3
• Avoid combination therapy with cefixime-ofloxacin despite some Indian studies suggesting benefit 7, as this contradicts international guidelines prioritizing azithromycin monotherapy and risks promoting further fluoroquinolone resistance 1, 2

Emerging Resistance Concerns

• Clinical failures with azithromycin are beginning to emerge in India, though it remains the best empirical choice 5
• Always narrow therapy based on susceptibility results when cultures become available 4, 3
• Local resistance patterns vary geographically and change over time, requiring ongoing surveillance 1