What is the recommended treatment for an otherwise healthy adult with uncomplicated enteric fever (typhoid or paratyphoid)?

Treatment of Uncomplicated Enteric Fever in Healthy Adults

Azithromycin 500 mg once daily for 7 days is the recommended first-line treatment for uncomplicated enteric fever in otherwise healthy adults. 1, 2

Initial Management

• Collect blood cultures before starting antibiotics whenever the patient is clinically stable, as blood cultures have 40-80% sensitivity in the first week of illness and remain the diagnostic gold standard 1, 3
• Start empiric treatment immediately after culture collection if the patient shows signs of sepsis, severe illness with documented fever ≥38.5°C, or clinical instability 1, 4

First-Line Antibiotic Choice

Azithromycin is superior to other options for the following evidence-based reasons:

• Clinical failure rates are significantly lower (OR 0.48) compared to fluoroquinolones 1, 2
• Hospital stays are approximately 1 day shorter than with fluoroquinolones 1, 2
• Relapse risk is dramatically reduced (OR 0.09) compared to ceftriaxone 1, 2
• Effective against multidrug-resistant strains, which is critical given that fluoroquinolone resistance exceeds 70% in South Asian isolates 1, 5

Dosing Regimen

• Adults: Azithromycin 500 mg orally once daily for 7 days 1
• Complete the full 7-day course even if fever resolves earlier, as premature discontinuation increases relapse risk to 10-15% 1

Alternative Agents (When Azithromycin Cannot Be Used)

Ceftriaxone for Severe Cases

• Ceftriaxone 1-2g IV/IM daily for 5-7 days is recommended for patients requiring parenteral therapy due to severe illness, inability to tolerate oral medications, or signs of complications 1, 6
• Relapse rates with ceftriaxone are <8% when full courses are completed 1

Fluoroquinolones (Geographic Restrictions Apply)

• Do NOT use ciprofloxacin empirically for cases from South or Southeast Asia, where resistance approaches 96% in some regions 1, 4, 5
• Ciprofloxacin 500-750 mg twice daily may be considered only if the patient traveled from sub-Saharan Africa or if susceptibility testing confirms sensitivity 1, 5
• Fluoroquinolone resistance exceeds 70% in South Asian isolates, making empiric use dangerous in this population 1

Chloramphenicol (Historical Option)

• Chloramphenicol is no longer recommended as first-line therapy due to safety concerns and availability of safer alternatives 7
• The FDA label states it should be used "only in those serious infections for which less potentially dangerous drugs are ineffective or contraindicated" 7

Expected Clinical Response

• Fever should clear within 4-5 days of appropriate antibiotic therapy 1, 5
• If fever persists beyond 48 hours in a clinically stable patient, reassess for alternative diagnoses or complications rather than empirically changing antibiotics 1
• Persistent fever beyond 3 days should trigger investigation for breakthrough infections or complications such as intestinal perforation 1, 4

Critical Pitfalls to Avoid

• Never discontinue antibiotics prematurely, even if fever resolves early—this increases relapse risk to 10-15% 1
• Never rely solely on the Widal test for diagnosis, as it has poor specificity (68.44%) and very poor positive predictive value (5.7%) 1
• Never use empiric ciprofloxacin for cases from Asia due to widespread resistance 1, 5
• Never miss signs of complications including intestinal perforation (typically occurring in week 3 if untreated), gastrointestinal bleeding, or encephalopathy, which occur in 10-15% of patients 1, 3, 5

Monitoring for Adverse Effects

• Common azithromycin side effects include nausea, vomiting, abdominal pain, and diarrhea—these are usually mild and self-limiting 1, 2
• Monitor for QT prolongation if the patient is on other QT-prolonging medications 1

When to Escalate Care

• Surgical consultation is required if intestinal perforation develops, which typically occurs in patients with illness duration exceeding 2 weeks 1
• Complications occur in 10-15% of patients and include gastrointestinal bleeding, perforation, and encephalopathy 1, 3