What is the recommended treatment for typhoid management?

Management of Typhoid Fever

Azithromycin 500 mg once daily for 7-14 days is the preferred first-line treatment for typhoid fever in adults, particularly given widespread fluoroquinolone resistance exceeding 70% in South Asia. 1, 2, 3

First-Line Treatment Regimen

• Azithromycin is the drug of choice for empiric treatment of typhoid fever 1, 2, 3
• Adult dosing: 500 mg orally once daily for 7-14 days 1, 2, 3
• Pediatric dosing: 20 mg/kg/day (maximum 1g/day) for 7-14 days 1, 2, 3
• Azithromycin demonstrates superior outcomes with significantly lower clinical failure rates (OR 0.48) compared to fluoroquinolones 1, 2
• Hospital stays are approximately 1 day shorter with azithromycin (mean difference -1.04 days) 1, 3
• Relapse risk is dramatically lower with azithromycin (OR 0.09) compared to ceftriaxone 1, 3

Why Fluoroquinolones Should NOT Be Used Empirically

• Never use ciprofloxacin empirically for cases from South or Southeast Asia - resistance rates exceed 70% and approach 96% in some regions 1, 2, 3, 4
• Fluoroquinolone resistance is particularly prevalent in travel-associated cases from South Asia 1, 2, 4
• Ciprofloxacin is FDA-approved for typhoid fever but only when susceptibility is confirmed 5
• The fluoroquinolone ofloxacin may be effective for multiply-resistant strains when susceptibility testing confirms sensitivity 6

Alternative Treatment Options

Ceftriaxone (for severe cases or parenteral therapy)

• Adult dosing: 1-2g IV/IM daily for 5-7 days 1, 2
• Pediatric dosing: 50-80 mg/kg/day (maximum 2g/day) IV/IM for 5-7 days 1, 2
• Ceftriaxone may result in decreased clinical failure compared to azithromycin (RR 0.42), though evidence is low certainty 7
• Time to defervescence may be 0.52 days shorter with ceftriaxone compared to azithromycin 7
• Once clinical improvement occurs with IV therapy, transition to oral azithromycin may be considered 2

Cefixime (NOT recommended as first-line)

• Avoid cefixime as first-line therapy - documented treatment failure rates of 4-37.6% 1, 3
• If cefixime must be used, mandatory test-of-cure at 1 week is required due to high failure rates 1
• Clinical failure, microbiological failure, and relapse rates are all increased with cefixime compared to fluoroquinolones 7
• Time to defervescence may be 1.74 days longer with cefixime compared to fluoroquinolones 7

Diagnostic Approach Before Treatment

• Obtain blood cultures before starting antibiotics whenever possible - highest yield within the first week of symptom onset 1, 2, 3
• Bone marrow culture remains the reference standard diagnostic method despite low sensitivity of blood culture 4
• For patients with sepsis features, start broad-spectrum antimicrobial therapy immediately after collecting blood cultures 1
• Look for gradual fever onset over 3-7 days with malaise, headache, and myalgia as typical presentation 4

Monitoring and Expected Clinical Response

• Expect fever clearance within 4-5 days of appropriate therapy 1, 2, 3
• If no clinical response by day 5, consider antimicrobial resistance or alternative diagnosis 1
• Mean fever clearance time with azithromycin is 5.8 days, compared to 7.1 days with cefixime and 8.2 days with ciprofloxacin 8
• Monitor for common azithromycin adverse effects: nausea, vomiting, abdominal pain, and diarrhea 1, 3
• Watch for potential drug interactions with azithromycin, particularly QT-prolonging medications 1, 3

Critical Pitfalls to Avoid

• Never discontinue antibiotics prematurely - complete the full 7-14 day course even if fever resolves early, as relapse occurs in 10-15% of inadequately treated cases 1, 2, 3
• Do not use ciprofloxacin empirically for travel-associated cases from South/Southeast Asia - resistance is nearly universal in these regions 1, 2, 3
• Avoid cefixime as first-line therapy without susceptibility testing due to high failure rates 1, 3
• Do not delay surgical intervention in cases with intestinal perforation 2, 3

Management of Complications

• Intestinal perforation occurs in 10-15% of patients when illness duration exceeds 2 weeks 1, 2, 3
• Life-threatening complications typically arise in the second week of untreated illness 4
• Surgical intervention with simple excision and closure is required for perforation, successful in up to 88.2% of cases 1, 2
• Treatment of intestinal complications is mainly conservative unless perforation occurs 9

Prevention Strategies

• Typhoid vaccination is recommended for travelers to endemic areas (Latin America, Asia, Africa) 1, 3, 4
• Two vaccine types available in the United States: Ty21a oral vaccine and Vi-polysaccharide parenteral vaccine 1
• Ty21a oral vaccine: One enteric-coated capsule on alternate days for total of four capsules, for adults and children ≥10 years 1
• Take with cool liquid no warmer than 37°C, approximately 1 hour before a meal; capsules must be kept refrigerated 1
• Booster doses for Ty21a should be repeated every 5 years 1
• Parenteral inactivated vaccine: 0.5 ml subcutaneously on two occasions separated by ≥4 weeks, with booster every 3 years 1
• Important limitation: Vaccination provides only 50-80% protection and 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, 3, 4
• Three vaccine types are now available for prevention of typhoid disease, including newer, more effective typhoid Vi-conjugate vaccines 4

Resistance Pattern Considerations

• Always consider local resistance patterns when selecting empiric therapy, as these vary geographically and change over time 1, 3
• Over 70% of S. typhi isolates from South Asia are fluoroquinolone-resistant 1
• Ciprofloxacin-resistant and ceftriaxone-resistant typhoid is common in Pakistan 4
• Extensively drug-resistant strains of enteric fever have emerged in Pakistan 7
• In some areas, susceptibility to old first-line antimicrobials like chloramphenicol has re-appeared 7