What is the recommended work up and treatment for a patient suspected of having typhoid fever?

Workup and Treatment for Suspected Typhoid Fever

Diagnostic Workup

For patients with suspected typhoid fever, obtain blood cultures immediately before initiating antibiotics, as this has the highest diagnostic yield (40-80% sensitivity) within the first week of symptom onset. 1

Essential Diagnostic Tests

• Blood cultures: Collect before antibiotic initiation; sensitivity is highest in the first week of illness (40-80%) 1
• Stool and urine cultures: These become positive after the first week with sensitivities of 35-65% and 0-58% respectively 1
• Bone marrow culture: Consider if blood cultures are negative, as this has higher sensitivity than blood cultures 1, 2
• Avoid the Widal serological test: This lacks adequate sensitivity and specificity and is not recommended 1

Clinical Features to Assess

• Gradual fever onset over 3-7 days with malaise, headache, and myalgia 3
• Fever documented in a medical setting, particularly temperatures ≥38.5°C 4
• Recent international travel history, especially to South Asia, Latin America, or Africa 1
• Duration of illness (complications more likely if >2 weeks) 1
• Signs of sepsis or severe systemic illness 4

Empiric Treatment

Patients with clinical features of sepsis who are suspected of having enteric fever should be treated empirically with broad-spectrum antimicrobial therapy after blood, stool, and urine culture collection. 4

First-Line Treatment Selection

Intravenous ceftriaxone 2g IV daily for 14 days is the preferred initial treatment, especially for patients with unstable clinical condition or those returning from Asia where fluoroquinolone resistance exceeds 70%. 1

Treatment Algorithm Based on Geography and Resistance:

• For patients from South Asia: Use ceftriaxone or azithromycin; avoid fluoroquinolones due to >70% resistance rates 1, 2
• For patients from other endemic areas with unknown resistance: Start with ceftriaxone 2g IV daily for adults 1
• For uncomplicated disease with confirmed susceptibility: Azithromycin 500mg once daily for 14 days is an acceptable oral alternative 1, 2

Critical Treatment Principles

• Duration must be 14 days regardless of fever resolution to reduce relapse risk 1, 2
• Narrow antimicrobial therapy when susceptibility results become available 4
• If isolate unavailable, tailor antimicrobial choice to susceptibility patterns from the acquisition setting 4

Fluoroquinolone Considerations

Fluoroquinolones should be avoided as first-line therapy in patients from South Asia due to resistance rates exceeding 70%. 1, 2

• If considering fluoroquinolones, ciprofloxacin disc testing alone is unreliable 1
• The organism must also be sensitive to nalidixic acid on disc testing to be considered truly fluoroquinolone-sensitive 1, 2
• When sensitive, fluoroquinolones have relapse rates <8% 2

Alternative Agents

• Azithromycin: Relapse rate <3%, resistance currently rare in many regions 1, 2
• Chloramphenicol: FDA-approved for acute Salmonella typhi infections; recommended to continue 8-10 days after patient becomes afebrile to lessen relapse possibility 5
• Cefixime: Has documented relapse rates of 4-37.6% and should not be first-line for recurrent cases 2

Monitoring and Expected Response

• Clinical improvement should occur within 4-5 days of appropriate therapy with fever clearance and symptom improvement 2
• Monitor daily for clinical deterioration suggesting complications (gastrointestinal bleeding, intestinal perforation, typhoid encephalopathy) which occur in 10-15% of patients 1
• Complications are more likely if illness duration exceeds 2 weeks before treatment 1

Common Pitfalls to Avoid

• Do not discontinue treatment when fever clears; this is a common error leading to relapse 2
• Do not use empiric ciprofloxacin for cases from Asia without confirmed nalidixic acid sensitivity 1, 2
• Do not use shorter treatment courses with ceftriaxone; this increases relapse rates 2
• Previous vaccination provides incomplete protection and does not protect against paratyphoid 1

Management of Treatment Failure or Relapse

• Obtain blood cultures immediately before restarting antibiotics 2
• Consider bone marrow culture if blood cultures negative (sensitivity 35-65%) 2
• Azithromycin is the preferred agent for recurrent cases at 500mg once daily for 14 days in adults 2
• Investigate for chronic gallbladder carriage with imaging and stool cultures if multiple relapses occur despite appropriate treatment 2