Typhoid Fever Diagnostic Criteria and Treatment
Diagnostic Criteria
Blood culture is the gold standard for diagnosing typhoid fever, with highest yield in the first week of symptoms (sensitivity 40-80%), and should be performed in all patients with suspected enteric fever. 1, 2
Clinical Presentation Required for Suspicion
- Fever (present in 97-100% of cases): sustained, high-grade fever with insidious onset over 3-7 days 2, 3
- Constitutional symptoms: headache, malaise, myalgia, and anorexia 2, 3
- Gastrointestinal symptoms: constipation or diarrhea (diarrhea is actually uncommon), abdominal discomfort, nonproductive cough 2
- Relative bradycardia may be present but is not reliable 2
Laboratory Diagnostic Approach
- Blood culture: Draw 2-3 specimens of 20 mL each (adults) prior to antibiotics; larger volumes needed due to low bacteremia (0.3 CFU/mL) 1
- Bone marrow culture: More sensitive than blood (especially if antibiotics already given), though more invasive 1
- Stool, duodenal fluid, and urine cultures: May be beneficial as adjuncts 1
- Culture-independent molecular diagnostics: Can be used from stool and blood when available 1
What NOT to Use for Diagnosis
- Widal test alone is insufficient and should not be used for diagnosis 2
- Serologic tests should not be used to diagnose enteric fever 1
- Peripheral white blood cell count and differential should not be performed to establish etiology 1
Treatment Algorithm
Step 1: Assess Severity and Geographic Origin
For severe cases (sepsis, fever ≥38.5°C in travelers from endemic areas, septic shock, or encephalopathy): Start IV ceftriaxone immediately after obtaining blood, stool, and urine cultures. 4, 5
For uncomplicated cases: Base treatment on travel history and local resistance patterns. 4
Step 2: Geographic Risk Stratification
Cases from South/Southeast Asia (High Fluoroquinolone Resistance)
- First-line: Azithromycin 500 mg once daily for 7-14 days 4, 5
- Alternative for severe cases: IV ceftriaxone (transition to oral when improved) 4, 5
- Relapse rate <8% 5
- Avoid ciprofloxacin empirically due to high resistance rates 4
Cases from Other Regions (If Susceptibility Confirmed)
- Fluoroquinolones (ciprofloxacin or ofloxacin): fever clearance <4 days, cure rates >96% 5, 6
- Alternative options: chloramphenicol, amoxicillin, or trimethoprim-sulfamethoxazole (if fully susceptible) 4
Step 3: Treatment Duration and Monitoring
- Continue treatment for 14 days to reduce relapse risk 5
- Expected fever clearance: 4-5 days with appropriate therapy 4
- Monitor for complications: intestinal perforation (typically week 3 if untreated), GI bleeding, encephalopathy (occur in 10-15% of patients) 2, 5
Critical Pitfalls to Avoid
- Do not use ciprofloxacin disc testing alone for susceptibility; organism must also be sensitive to nalidixic acid to confirm fluoroquinolone susceptibility 5
- Do not delay treatment in unstable patients waiting for culture results; early treatment improves outcomes 5
- Do not miss complications: watch for signs of intestinal perforation, GI bleeding, or septic shock 2
- Do not rely on "step-ladder" fever pattern; this classic finding is not reliably present 2
Special Considerations
Empiric Treatment Before Culture Results
For immunocompetent adults with suspected typhoid and fever ≥38.5°C from endemic areas:
- Azithromycin or ceftriaxone (depending on severity) 1, 4
- For children <3 months: third-generation cephalosporin 1
Severe Cases Requiring Steroids
- Consider adding steroids in severe typhoid fever 5