What is the recommended treatment for typhoid?

Typhoid Fever Treatment

For typhoid fever, initiate intravenous ceftriaxone 2g daily for 14 days as first-line therapy, particularly for patients with unstable clinical condition or those with exposure to South Asia where fluoroquinolone resistance exceeds 70%. 1

First-Line Treatment Selection

Preferred Initial Therapy

• Intravenous ceftriaxone is the preferred first-line agent, administered at 2g IV daily for adults for a full 14-day course to minimize relapse risk 1
• This recommendation is especially critical given that fluoroquinolone resistance now exceeds 70% in isolates from Asia, making older fluoroquinolones unreliable 1
• Ceftriaxone remains effective even in regions with extensive multidrug resistance (MDR) and nalidixic acid resistance (NaR) 1

Oral Alternative for Uncomplicated Disease

• Azithromycin is the preferred oral option for uncomplicated typhoid fever, particularly when fluoroquinolone resistance is documented 1
• Azithromycin demonstrates superior efficacy compared to ofloxacin in MDR/NaR typhoid, with clinical cure rates of 82% versus 64% and significantly shorter fever clearance times (5.8 days vs 8.2 days) 2
• Resistance to azithromycin remains rare in most regions, making it a reliable choice 1
• Both gatifloxacin and azithromycin showed equivalent excellent efficacy in Vietnam (2004-2005), with median fever clearance of 106 hours for both agents 3

Critical Treatment Considerations Based on Geographic Origin

South Asian Exposure - Avoid Fluoroquinolones

• Fluoroquinolones should NOT be used as first-line therapy for patients with South Asian exposure due to resistance rates exceeding 70% 1
• Ciprofloxacin is specifically listed as an FDA-approved treatment for typhoid fever 4, but this approval predates widespread resistance and should not guide current practice in high-resistance regions 1, 5
• Pakistan has particularly high rates of both ciprofloxacin-resistant and ceftriaxone-resistant typhoid 5

Testing Pitfall to Avoid

• 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
• This is a critical laboratory interpretation error that can lead to treatment failure if overlooked 1

Treatment Duration and Monitoring

Standard Course

• Complete the full 14-day course of ceftriaxone to reduce relapse risk 1
• For azithromycin, a 7-day course at 10-20 mg/kg/day is effective 3, 2

Complications Requiring Vigilance

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

When Fluoroquinolones May Still Be Considered

Gatifloxacin as Newer-Generation Option

• Gatifloxacin (a newer fluoroquinolone) demonstrated effectiveness even in populations with high NaR prevalence, significantly reducing clinical failure compared to cefixime (RR 0.04) 6
• Gatifloxacin showed equivalent efficacy to azithromycin in Vietnam with both drugs performing well 3, 6
• However, gatifloxacin should only be used when local susceptibility data confirm effectiveness 1

Geographic Considerations

• In regions outside South Asia with documented fluoroquinolone susceptibility, these agents may be considered 5
• Always verify both ciprofloxacin AND nalidixic acid sensitivity before using any fluoroquinolone 1

Important Caveats

• Previous typhoid vaccination provides incomplete protection and does not protect against paratyphoid fever 1
• Treatment choice must be guided by local resistance patterns, as resistance evolves over time 5, 6
• The cost of gatifloxacin is approximately one-third that of azithromycin in some settings, which may influence selection when both are equally effective 3