What is the recommended antimicrobial treatment for an adult with enteric fever (typhoid/paratyphoid) who has no known drug allergies?

Recommended Antimicrobial Treatment for Enteric Fever in Adults

For adults with enteric fever and no drug allergies, azithromycin 500-1000 mg orally daily for 7 days is the preferred first-line treatment, particularly for infections acquired from South Asia where fluoroquinolone resistance exceeds 70%. 1, 2

Treatment Selection Based on Geographic Origin

Infections from South Asia (India, Pakistan, Bangladesh, Nepal)

• Start azithromycin 500-1000 mg orally daily for 7 days as empiric therapy due to widespread fluoroquinolone resistance (87-98% of isolates) 1, 3
• Azithromycin demonstrates superior outcomes compared to fluoroquinolones in regions with drug-resistant strains, with lower clinical failure rates (OR 0.48,95% CI 0.26-0.89) and shorter hospital stays (1 day reduction) 4, 5
• Avoid ciprofloxacin empirically for South Asian cases—over 70% of S. Typhi isolates from this region are fluoroquinolone-resistant 4, 1
• Pakistan has additional concern for extensively drug-resistant (XDR) strains (64% of isolates), which are resistant to fluoroquinolones AND third-generation cephalosporins 3

Infections from Sub-Saharan Africa

• Ciprofloxacin 500 mg orally twice daily for 7-10 days remains an acceptable alternative for African-acquired cases, as fluoroquinolone resistance rates are lower 4, 2, 6
• Fluoroquinolones achieve fever clearance within 4 days, cure rates >96%, and low relapse rates (<8%) when organisms are susceptible 4

Severe or Hospitalized Cases

• Ceftriaxone 2 g IV daily for 5-7 days for patients with sepsis, altered mental status, or inability to tolerate oral therapy 1, 2
• Switch to oral azithromycin once clinically improved and afebrile for 24 hours to complete 7-14 days total treatment 1
• Ceftriaxone shows lower treatment failure compared to gatifloxacin in culture-confirmed cases (HR 0.24,95% CI 0.08-0.73) 4

Critical Management Steps

Before Starting Antibiotics

• Obtain blood cultures immediately—highest yield within first week of symptoms (40-80% sensitivity) 4, 2
• Collect stool and urine cultures if sepsis suspected, as these become positive after the first week 4
• Do NOT delay treatment in clinically unstable patients; start empiric therapy after cultures obtained 4, 2

Antibiotic Susceptibility Testing Pitfalls

• Never rely on ciprofloxacin disc testing alone to determine fluoroquinolone susceptibility 4
• The organism must ALSO be sensitive to nalidixic acid on disc testing to be considered truly fluoroquinolone-susceptible 4
• Azithromycin susceptibility testing is not readily available, but resistance remains rare (<3% globally) 4

Alternative Regimens (When First-Line Options Unavailable)

For Susceptible Isolates

• Ofloxacin 400 mg orally twice daily for 7-10 days if confirmed fluoroquinolone-susceptible 2
• Chloramphenicol may be considered only as last resort when no other options available, though resistance patterns have changed 4, 1

Oral Step-Down Options

• Cefixime 400 mg orally once daily can be used but has higher treatment failure rates (4-37.6%) compared to other options 4
• Azithromycin remains preferred oral follow-on agent for fluoroquinolone-resistant cases 4

Treatment Duration and Monitoring

• Complete 7-14 days of appropriate antibiotic therapy to reduce relapse risk 4, 1
• Azithromycin has lowest relapse rates (<3%) compared to ceftriaxone (<8%) and fluoroquinolones 4
• Expect fever clearance within 4-5 days of appropriate therapy 4, 1
• Narrow therapy based on susceptibility results when available 2

Common Pitfalls to Avoid

• Do not assume all enteric fever is fluoroquinolone-susceptible—resistance is now the norm in South Asia, not the exception 4, 1, 3
• Do not use cefixime as first-line empiric therapy—it has unacceptably high failure rates and should be reserved for confirmed susceptible isolates 4
• Do not stop antibiotics early—inadequate treatment duration increases relapse risk, which can occur up to one month after initial treatment 7
• Do not forget to consider upper GI bleeding—though rare, gastric ulcers can develop and cause life-threatening hemorrhage 7

Special Considerations

Infants Under 3 Months

• Use third-generation cephalosporin (ceftriaxone) rather than azithromycin or fluoroquinolones 1, 8

Asymptomatic Contacts

• Do not offer empiric treatment to asymptomatic contacts; implement infection control measures instead 2

Persistent Symptoms

• Reassess fluid/electrolyte balance, nutritional status, and consider treatment failure or complications 2
• Repeat blood cultures if fever persists beyond 5 days of appropriate therapy 1