What oral maintenance options are appropriate after intravenous ceftriaxone for enteric (typhoid) fever?

Oral Maintenance After IV Ceftriaxone for Enteric Fever

For patients with enteric fever who have clinically improved on IV ceftriaxone, azithromycin is the preferred oral maintenance agent, particularly when fluoroquinolone resistance is confirmed or suspected, with treatment continued for a total duration of 14 days. 1

Treatment Algorithm Based on Susceptibility

When Fluoroquinolone Resistance is Confirmed or Suspected (Most Asian Cases)

• Switch to oral azithromycin once the patient is clinically stable, afebrile, and able to tolerate oral medications 1
• Azithromycin has a relapse rate <3%, which is superior to ceftriaxone's <8% relapse rate 1
• Continue treatment for a total of 14 days (combining IV and oral therapy) to minimize relapse risk 1
• Over 70% of S. typhi and S. paratyphi isolates imported into the UK from Asia are fluoroquinolone-resistant, making azithromycin the most reliable oral option 1

When Isolate is Fluoroquinolone-Sensitive (Confirmed by Nalidixic Acid Sensitivity)

• Switch to oral fluoroquinolone (ciprofloxacin or ofloxacin) for completion of therapy 1
• Fluoroquinolones achieve fever clearance in <4 days with cure rates >96% in sensitive isolates 1
• Total treatment duration should be 14 days 1
• Critical caveat: Ciprofloxacin disc testing alone is unreliable; the organism must also be sensitive to nalidixic acid on disc testing to be considered truly fluoroquinolone-sensitive 1

Cefixime as an Alternative (Use with Caution)

• Oral cefixime can be considered as an alternative oral agent, but has reported treatment failure rates of 4-37.6% 1
• This high failure rate makes cefixime a less desirable option compared to azithromycin 1
• If used, continue for a total of 14 days of therapy 2

Clinical Criteria for Switching to Oral Therapy

The patient must meet ALL of the following criteria before transitioning to oral maintenance 2:

• Afebrile or clinically improving
• Hemodynamically stable
• Able to tolerate oral medications
• No evidence of complications (gastrointestinal bleeding, intestinal perforation, or typhoid encephalopathy) 1

Duration of IV Ceftriaxone Before Switching

• Research supports that 5-7 days of IV ceftriaxone is adequate before switching to oral therapy in uncomplicated cases 3, 4, 5
• Some patients may be switched earlier (after 3-5 days) if clinically stable and improving 4, 5, 6
• The key is achieving clinical stability and defervescence, then continuing oral therapy to complete 14 days total 3, 4

Important Pitfalls to Avoid

• Do not use ciprofloxacin disc testing alone to determine fluoroquinolone sensitivity; nalidixic acid sensitivity must also be confirmed 1
• Avoid treatment courses shorter than 14 days total, as this increases relapse risk significantly 1
• Do not assume fluoroquinolone sensitivity in patients returning from Asia, where resistance exceeds 70% 1
• Monitor for relapse even after appropriate treatment, as complications (bleeding, perforation, encephalopathy) are more likely if illness duration exceeds 2 weeks before treatment 1

Geographic Considerations

• For patients returning from sub-Saharan Africa, fluoroquinolones may still be appropriate first-line agents if sensitivity is confirmed 1
• For patients from Asia (particularly South and Southeast Asia), empiric azithromycin is preferred due to high fluoroquinolone resistance rates 1