How do you manage a patient with typhoid fever?

Management of Typhoid Fever

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

Immediate Diagnostic Steps

• Obtain blood cultures before starting antibiotics whenever possible, as they have the highest yield (40-80% sensitivity) within the first week of symptom onset 3, 2, 4
• If the patient is clinically unstable or has sepsis features, start empiric treatment immediately after collecting blood cultures 1, 2
• Stool and urine cultures become positive after the first week, with sensitivities of 35-65% and 0-58% respectively 3, 4
• Never rely on the Widal test for diagnosis—it has poor specificity (68.44%) and very poor positive predictive value (5.7%) 2
• Bone marrow cultures have higher sensitivity than blood cultures but are rarely needed 3, 4

First-Line Treatment Algorithm

For Uncomplicated Disease (Oral Therapy)

• Azithromycin 500 mg once daily for 7 days in adults 1, 2
• Azithromycin 20 mg/kg/day (maximum 1g/day) for 7 days in children 1, 2
• Azithromycin demonstrates significantly lower clinical failure rates (OR 0.48) compared to fluoroquinolones 1, 2
• Hospital stays are approximately 1 day shorter with azithromycin compared to fluoroquinolones 1, 2
• Relapse risk is dramatically lower with azithromycin (OR 0.09) compared to ceftriaxone 1, 2

For Severe Cases or Unstable Patients (IV Therapy)

• Ceftriaxone 2g IV/IM once daily for adults 3, 4
• Ceftriaxone 50-80 mg/kg/day (maximum 2g/day) IV/IM for children 1, 2
• Continue for 5-7 days, though some guidelines recommend 14 days to reduce relapse risk 3, 4
• All S. typhi isolates reported to the UK Health Protection Agency in 2006 were sensitive to ceftriaxone 3

Geographic Considerations and Resistance Patterns

• Never use ciprofloxacin empirically for cases from South or Southeast Asia, where resistance approaches 96% in some regions 1, 2
• More than 70% of S. typhi and S. paratyphi isolates imported into the UK are fluoroquinolone-resistant 3, 1, 4
• When testing isolates for antibiotic sensitivity, ciprofloxacin disc testing alone is unreliable—the organism must also be sensitive to nalidixic acid on disc testing to be considered truly sensitive to fluoroquinolones 3, 4
• Fluoroquinolones (ciprofloxacin or ofloxacin) remain effective only when susceptibility is confirmed, primarily for cases from sub-Saharan Africa 1, 2

Monitoring and Expected Response

• Expect fever clearance within 4-5 days of appropriate antibiotic therapy 1, 2, 5
• If no clinical response by day 5, consider antimicrobial resistance or alternative diagnosis 1
• Complete the full 7-day course (or 14 days per some guidelines) to prevent relapse, which occurs in 10-15% of inadequately treated cases 3, 1, 2
• Relapse rates are <8% for ceftriaxone and <3% for azithromycin when full courses are completed 3

Management of Complications

• Complications such as gastrointestinal bleeding, intestinal perforation, and typhoid encephalopathy occur in 10-15% of patients 3, 4
• These complications are more likely if illness duration exceeds 2 weeks 3, 4
• Intestinal perforation requires surgical intervention with simple excision and closure, with success rates up to 88.2% 1
• Consider adding corticosteroids in severe cases 3

Critical Pitfalls to Avoid

• Never discontinue antibiotics prematurely, even if fever resolves early—incomplete treatment leads to 10-15% relapse rates 1, 2
• Never use empiric ciprofloxacin for cases from Asia due to widespread resistance 1, 2
• Avoid cefixime as first-line therapy—it has documented treatment failure rates of 4-37.6% and performs worse than fluoroquinolones 1, 6
• If cefixime must be used, a mandatory test-of-cure at 1 week is required due to high failure rates 1
• Do not rely on the Widal test for diagnosis—supplement with blood cultures 2

Adverse Effects to Monitor

• Common azithromycin adverse effects include gastrointestinal symptoms: nausea, vomiting, abdominal pain, and diarrhea 1, 2
• Monitor for potential drug interactions with azithromycin, particularly QT-prolonging medications 1, 2
• Ceftriaxone is generally well-tolerated with few adverse effects 5, 6

Prevention Strategies

• Typhoid vaccination is recommended for travelers to endemic areas, particularly Latin America, Asia, and Africa 1, 4
• Vaccination provides only 50-80% protection and does not protect against paratyphoid 1
• Hand hygiene and appropriate food and water safety precautions remain essential even after vaccination 1, 4