How should I treat an adult patient with typhoid fever who has no known drug allergies?

Treatment of Typhoid Fever in Adults

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. 1, 2

Immediate Diagnostic Steps Before Treatment

• Obtain blood cultures immediately before starting antibiotics – blood cultures have 40-80% sensitivity and provide the highest diagnostic yield within the first week of symptom onset 1, 2, 3
• Collect multiple large-volume specimens (20 mL each) to maximize sensitivity 3
• If the patient is clinically unstable or shows signs of sepsis, start empiric treatment immediately after collecting cultures 1
• Obtain baseline complete blood count (looking for lymphopenia and thrombocytopenia), comprehensive metabolic panel, and liver function tests 2, 3
• Exclude malaria in all febrile travelers from tropical areas using both thick/thin smears and rapid diagnostic tests 2, 3

First-Line Antibiotic Treatment Algorithm

For Uncomplicated Cases (Oral Therapy)

Azithromycin is the preferred first-line agent:

• Dose: 500 mg once daily for 7 days (some guidelines recommend 14 days to minimize relapse risk) 1, 2
• Azithromycin demonstrates significantly lower clinical failure rates (OR 0.48) compared to fluoroquinolones 1
• Hospital stays are approximately 1 day shorter with azithromycin versus fluoroquinolones 1
• Relapse risk is dramatically lower (OR 0.09) compared to ceftriaxone, with relapse rates <3% 1, 2

For Severe Cases (IV Therapy Required)

Ceftriaxone is the first-line IV agent:

• Dose: 1-2 g IV/IM once daily for 5-7 days (extend to 14 days to reduce relapse risk) 1, 2
• Particularly important for patients from Asia where >70% of isolates are fluoroquinolone-resistant 1, 2
• Relapse rates <8% when full courses are completed 1, 2

Critical Geographic Considerations

• Never use ciprofloxacin empirically for cases from South or Southeast Asia – resistance approaches 96% in some regions 1, 2
• Fluoroquinolone resistance exceeds 70% in isolates from South Asia 1, 2
• Ciprofloxacin remains an alternative only if the patient traveled from sub-Saharan Africa AND nalidixic acid sensitivity is confirmed 1, 2
• Pakistan has widespread ciprofloxacin-resistant and ceftriaxone-resistant typhoid 4

Expected Clinical Response and Monitoring

• Expect fever clearance within 4-5 days of appropriate antibiotic therapy 1, 2
• With susceptible organisms, fluoroquinolones achieve fastest fever clearance (often <4 days) 2
• If fever persists beyond 48 hours in a clinically stable patient, reassess for alternative diagnoses or complications rather than empirically changing antibiotics 1
• Persistent fever beyond 3 days despite empirical therapy should trigger investigation for breakthrough infections or complications 1

Treatment Duration to Prevent Relapse

• Complete a full 14-day antibiotic course to minimize relapse risk, even if fever resolves earlier 1, 2
• Relapse occurs in 10-15% of inadequately treated cases 1
• Never discontinue antibiotics prematurely, even if fever resolves early 1

Complications to Monitor

• Life-threatening complications (intestinal perforation, encephalopathy, gastrointestinal bleeding) occur in 10-15% of patients, typically in the second week of untreated illness 1, 2
• Intestinal perforation typically occurs in patients with illness duration exceeding 2 weeks 1
• Perform serial neurologic examinations regularly to detect encephalopathy 3
• If perforation occurs, surgical intervention with simple excision and closure is required, with success rates up to 88.2% 1

Adjunctive Therapy

• Consider corticosteroids in severe cases with toxic/delirious state or encephalopathy 2, 5
• Supportive care with appropriate fluid and electrolyte management is essential 5

Common Pitfalls to Avoid

• Never rely solely on the Widal test for diagnosis – it has poor specificity (68.44%) and very poor positive predictive value (5.7%) 1
• Never use empiric ciprofloxacin for cases from Asia due to widespread resistance 1, 2
• Never discontinue antibiotics prematurely, even if fever resolves early 1

Adverse Effects to Monitor

• Common azithromycin adverse effects include gastrointestinal symptoms: nausea, vomiting, abdominal pain, and diarrhea 1
• Monitor for potential drug interactions with azithromycin, particularly QT-prolonging medications 1

Infection Control and Public Health

• Typhoid fever is a nationally notifiable disease – report immediately to local/state health departments with isolate submission for antimicrobial susceptibility testing 2, 3
• Implement contact precautions with gloves and gowns, plus hand hygiene with soap and water (not alcohol alone) 3
• Asymptomatic carriers in high-risk settings (healthcare, food service, childcare) should be treated according to local public health guidance 6