What is the recommended treatment for a patient with suspected typhoid fever, presenting with fever for 2 days, negative Typhidot IgM and IgG tests, and a Widal test result of 1:160 with both H and O positive?

Treatment Recommendation for Suspected Typhoid Fever

Start empiric antibiotic therapy immediately with azithromycin 20 mg/kg/day (maximum 1g/day) orally for 7 days, or ceftriaxone 50-80 mg/kg/day (maximum 2g/day) IV for 5-7 days if the patient appears severely ill, while obtaining blood cultures before the first antibiotic dose. 1, 2

Diagnostic Interpretation

Your serological test results are unreliable and should not guide treatment decisions:

• The Widal test lacks sensitivity and specificity and is not recommended for diagnosis of typhoid fever. 3 A titer of 1:160 can occur in healthy individuals in endemic areas and does not confirm acute infection.

• Negative Typhidot IgM and IgG tests do not rule out typhoid fever, especially only 2 days into illness, as these rapid serological tests have shown mixed results in clinical validation. 3

• Blood cultures remain the gold standard with 40-80% sensitivity in the first week of symptoms and should be obtained immediately before starting antibiotics. 1, 2

Empiric Treatment Selection

Given only 2 days of fever and the clinical suspicion for typhoid:

• Azithromycin is the preferred first-line agent for uncomplicated cases, showing 94% cure rates in children with typhoid fever and dramatically lower relapse rates (OR 0.09) compared to ceftriaxone. 2, 4

• Ceftriaxone should be used for severe presentations including signs of sepsis, inability to tolerate oral medications, or clinical instability requiring hospitalization. 1, 2

• Avoid fluoroquinolones empirically as over 70% of S. typhi and S. paratyphi isolates are now resistant to this class, particularly from South Asian sources. 3, 1, 4

Treatment Duration Critical Point

Extend treatment to 14 days regardless of which antibiotic is chosen to minimize relapse risk, which occurs in 10-15% of inadequately treated cases. 1, 4 This is essential even though initial courses of 5-7 days show clinical response, as:

• Azithromycin relapse rates are <3% with 14-day courses 1
• Ceftriaxone relapse rates are <8% with adequate duration 3, 1

Expected Clinical Response

• Fever should clear within 4-5 days of appropriate therapy. 4, 2

• If no improvement occurs within 24-48 hours, consider resistant organisms, alternative diagnoses (malaria, dengue, rickettsial infections), or complications. 3, 2

• Switch from IV to oral therapy once the patient shows clinical improvement and has been afebrile for 24 hours. 2

Antibiotic Susceptibility Testing

When culture results return positive:

• Request nalidixic acid sensitivity testing, as ciprofloxacin disc testing alone is unreliable for determining fluoroquinolone susceptibility in Salmonella species. 3, 4

• Narrow therapy based on susceptibility results but maintain the 14-day total duration. 2

Common Pitfalls to Avoid

• Do not wait for culture confirmation to start antibiotics in clinically suspected cases, as blood culture sensitivity is only 40-80% and delays worsen outcomes. 1

• Do not rely on the Widal test result of 1:160 to make treatment decisions, as this test is not recommended due to poor diagnostic accuracy. 3

• Do not use shorter treatment courses (5-7 days only) despite clinical improvement, as this significantly increases relapse rates. 1, 4

• Do not use cefixime as first-line therapy, as it has reported treatment failure rates of 4-37.6%. 3