What is the recommended treatment for typhoid?

Typhoid Fever Treatment

First-Line Treatment Recommendation

For typhoid fever, initiate intravenous ceftriaxone 2g daily for 14 days as the preferred first-line treatment, especially for patients with unstable clinical condition or those returning from Asia where fluoroquinolone resistance exceeds 70%. 1

Treatment Algorithm Based on Clinical Presentation and Geographic Origin

Severe or Hospitalized Patients

• Intravenous ceftriaxone 2g daily for 14 days is the preferred regimen for adults with unstable clinical condition 1
• This 14-day duration reduces relapse risk, which occurs in 10-15% of patients when illness duration exceeds 2 weeks 1
• Ceftriaxone demonstrates effectiveness with low clinical failure rates and few adverse effects 2

Uncomplicated Disease with Oral Therapy Option

• Azithromycin is the preferred oral alternative for uncomplicated disease, particularly when fluoroquinolone resistance is confirmed, as azithromycin resistance remains rare in most regions 1
• Azithromycin (10 mg/kg/day for 7 days) may result in shorter fever clearance time (mean 5.8 days) compared to fluoroquinolones (mean 8.2 days) in multidrug-resistant and nalidixic acid-resistant typhoid 3
• Azithromycin also reduces convalescent fecal carriage more effectively than fluoroquinolones (1.6% vs 19.4%) 3

Geographic Considerations for Fluoroquinolone Use

Critical caveat: Fluoroquinolones should be avoided as first-line therapy in patients returning from South Asia, where resistance exceeds 70%. 1

• Ciprofloxacin is FDA-approved for typhoid fever 4, but its use must be guided by resistance patterns 5
• When considering fluoroquinolones, 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
• In regions without high fluoroquinolone resistance, ciprofloxacin 500 mg twice daily for 7 days remains an option 6
• Ciprofloxacin-resistant and ceftriaxone-resistant typhoid is now common in Pakistan 5

Alternative Oral Cephalosporin Option

• Cefixime may be considered but performs less well than fluoroquinolones in susceptible strains, with increased clinical failure (RR 13.39), microbiological failure (RR 4.07), and relapse rates (RR 4.45) 2
• However, in a 2003-04 Pakistani study with high resistance rates, cefixime showed no clinical or microbiological failures when used for 7 days 1

Comparative Performance: Ceftriaxone vs Azithromycin

• Ceftriaxone may result in decreased clinical failure compared to azithromycin (RR 0.42) 2
• Time to defervescence may be 0.52 days shorter with ceftriaxone compared to azithromycin 2
• Both agents demonstrate good efficacy in contemporary practice 1

Duration of Treatment

The standard treatment duration is 14 days for ceftriaxone to minimize relapse risk. 1 Shorter courses (7 days) have been studied for oral agents like azithromycin and fluoroquinolones but carry higher relapse rates 3, 6

Monitoring for Complications

• Complications including gastrointestinal bleeding, intestinal perforation, and typhoid encephalopathy occur in 10-15% of patients, particularly when illness duration exceeds 2 weeks before treatment 1
• Blood cultures have highest yield (40-80% sensitivity) within the first week of symptoms 1

Key Clinical Pitfalls to Avoid

• Do not rely on ciprofloxacin disc testing alone—nalidixic acid sensitivity must also be confirmed 1
• Do not use fluoroquinolones empirically for patients from South Asia without confirmed susceptibility 1
• Do not use shorter treatment courses than recommended, as this increases relapse risk 1
• Previous typhoid vaccination provides incomplete protection and does not protect against paratyphoid 1