What is the recommended treatment for a patient presenting with typhoid fever?

Treatment of Typhoid Fever

Azithromycin 500 mg once daily for 7-14 days is the preferred first-line treatment for adults with typhoid fever, particularly given widespread fluoroquinolone resistance exceeding 70% in endemic regions. 1, 2

First-Line Treatment Algorithm

For Adults

• Start azithromycin 500 mg orally once daily for 7-14 days as empiric therapy, especially for cases originating from South Asia where fluoroquinolone resistance approaches 96% 1, 2
• Obtain blood cultures before initiating antibiotics when possible, as they have the highest yield (40-80% sensitivity) within the first week of symptoms 3, 4

For Children

• Azithromycin 20 mg/kg/day (maximum 1g/day) for 7-14 days is the recommended pediatric dose 1, 2

For Severely Ill or Unstable Patients

• Ceftriaxone 2g IV daily for 14 days should be used when the patient's clinical condition is unstable or they cannot tolerate oral therapy 3, 4
• All isolates reported to surveillance systems remain sensitive to ceftriaxone 3

Why Azithromycin Over Other Options

Azithromycin demonstrates superior clinical outcomes:

• Lower risk of treatment failure (OR 0.48) compared to fluoroquinolones 1, 2
• Hospital stays approximately 1 day shorter (mean difference -1.04 days) 1, 2
• Dramatically lower relapse risk (OR 0.09) compared to ceftriaxone 1, 2
• Resistance to azithromycin remains rare in most regions 3, 4

Fluoroquinolones should be avoided empirically because resistance exceeds 70% in isolates imported from Asia, with some regions approaching 96% resistance 3, 1, 2

Critical Pitfalls to Avoid

Never Use Ciprofloxacin Empirically for Travel-Associated Cases

• More than 70% of S. typhi and S. paratyphi isolates from South/Southeast Asia are fluoroquinolone-resistant 3, 1, 2
• Ciprofloxacin disc testing alone is unreliable for determining true fluoroquinolone sensitivity 3, 4
• The organism must also be sensitive to nalidixic acid on disc testing to be considered truly fluoroquinolone-sensitive 3, 4

Avoid Cefixime as First-Line Therapy

• Cefixime has documented treatment failure rates of 4-37.6% 3, 5
• If cefixime must be used, mandatory test-of-cure at 1 week is required 1
• Clinical failure may be increased 13-fold compared to fluoroquinolones (RR 13.39,95% CI 3.24-55.39) 5

Complete the Full Antibiotic Course

• Do not discontinue antibiotics prematurely even if fever resolves early 1, 2
• Relapse occurs in 10-15% of inadequately treated cases 1, 2, 4
• Treatment should be continued for the full 7-14 days to reduce relapse risk 3, 1

Expected Clinical Response and Monitoring

Fever Clearance Timeline

• Expect fever clearance within 4-5 days of appropriate antibiotic therapy 1, 2, 4
• If no clinical response by day 5, consider antimicrobial resistance or alternative diagnosis 2
• Mean defervescence time with ceftriaxone is approximately 4 days when complications are excluded 6

Common Adverse Effects of Azithromycin

• Monitor for gastrointestinal symptoms: nausea, vomiting, abdominal pain, and diarrhea 1, 2
• Watch for potential drug interactions with QT-prolonging medications 1, 2

Management of Complications

Intestinal Perforation

• Occurs in 10-15% of patients when illness duration exceeds 2 weeks 1, 2, 4
• Requires immediate surgical intervention with simple excision and closure 1, 2
• Surgical success rates reach up to 88.2% 1, 2

Other Severe Complications

• Gastrointestinal bleeding and typhoid encephalopathy can occur in 10-15% of patients 4
• Life-threatening complications typically arise in the second week of untreated illness 7

Alternative Treatment Options When Susceptibility is Confirmed

Fluoroquinolones (Only for Susceptible Isolates)

• Ciprofloxacin remains effective when susceptibility is confirmed, with fever clearance time <4 days, cure rates >96%, and relapse rates <8% 3, 7
• However, ciprofloxacin is FDA-approved for typhoid fever but should only be used when local resistance patterns support its use 8
• Ofloxacin and enoxacin achieved 100% cure rates without relapse in older studies 9

Ceftriaxone Dosing Details

• Adults: 2g IV daily for 14 days 4
• Children: 50-80 mg/kg/day (maximum 2g/day) IV/IM for 5-7 days, though 14 days reduces relapse 2, 6, 10
• Higher doses (not less than 3g once daily) or longer duration may be needed to reduce relapse incidence 9

Prevention Strategies

Vaccination Recommendations

• Typhoid vaccination is recommended for travelers to endemic areas (Latin America, Asia, Africa) with moderate to high risk of exposure 1, 2, 4
• Two vaccines available in the United States: Ty21a oral vaccine and Vi-polysaccharide parenteral vaccine 1

Important Vaccination Limitations

• Vaccination provides only 50-80% protection 1, 2, 4
• Does not protect against Salmonella Paratyphi 1, 2, 4
• Hand hygiene and food/water safety precautions remain essential and should not be replaced by vaccination alone 1, 2, 4