What is the appropriate antibiotic treatment for a patient suspected of having typhoid fever?

Antibiotic Treatment for Typhoid Fever

Azithromycin 500 mg once daily for 7 days is the preferred first-line treatment for adults with suspected typhoid fever, particularly given that fluoroquinolone resistance now exceeds 70% in most endemic regions. 1, 2

First-Line Treatment Recommendations

Adults

• Azithromycin 500 mg orally once daily for 7 days 1, 2
• This demonstrates superior outcomes with lower clinical failure rates (OR 0.48) compared to fluoroquinolones 1
• Hospital stays are approximately 1 day shorter compared to fluoroquinolones 1
• Relapse risk is dramatically lower (OR 0.09) compared to ceftriaxone 1

Children

• Azithromycin 20 mg/kg/day (maximum 1g/day) orally for 7 days 1, 2

Severe Cases Requiring IV Therapy

• Ceftriaxone 1-2g IV/IM daily for 5-7 days in adults 1, 2
• Ceftriaxone 50-80 mg/kg/day (maximum 2g/day) IV/IM for 5-7 days in children 1, 2

Critical Geographic Considerations

Never use ciprofloxacin empirically for cases from South or Southeast Asia - resistance approaches 96% in some regions and exceeds 70% overall in South Asian isolates. 3, 1, 2, 4

• Ciprofloxacin 500 mg twice daily for 10 days remains an option ONLY if the patient traveled from sub-Saharan Africa where susceptibility is confirmed 3, 5
• Over 70% of S. typhi isolates imported into the UK from Asia are fluoroquinolone-resistant 3
• All isolates reported to the UK Health Protection Agency in 2006 remained sensitive to ceftriaxone 3

Diagnostic Approach Before Treatment

• Obtain blood cultures before starting antibiotics whenever possible - they have the highest yield (40-80% sensitivity) within the first week of symptom onset 3, 1, 6
• Stool and urine cultures become positive after the first week 3
• Do not rely on the Widal test - it has poor specificity (68.44%) and very poor positive predictive value (5.7%) 6
• For patients with sepsis features, start broad-spectrum antimicrobial therapy immediately after collecting blood cultures 3, 1

Expected Clinical Response and Monitoring

• Fever should clear within 4-5 days of appropriate antibiotic therapy 3, 1, 2, 6
• If no clinical improvement by day 5, consider antimicrobial resistance or alternative diagnosis 1
• Complete the full 7-day course even if fever resolves early - relapse occurs in 10-15% of inadequately treated cases 1, 2, 6
• Relapse rates when full courses are completed: <3% for azithromycin, <8% for ceftriaxone 3, 1

Alternative Treatments (Based on Resistance Patterns)

When Azithromycin is Not Available or Appropriate

• Ceftriaxone remains highly effective with 100% sensitivity in most regions 7, 8
• Ceftriaxone may result in decreased clinical failure compared to azithromycin (RR 0.42) 8
• Time to defervescence may be 0.52 days shorter with ceftriaxone compared to azithromycin 8

Cefixime Should Be Avoided as First-Line

• Cefixime has documented treatment failure rates of 4-37.6% 3, 1
• Clinical failure is significantly increased compared to fluoroquinolones (RR 13.39) 8
• If cefixime must be used, mandatory test-of-cure at 1 week is required 1
• The WHO lists cefixime only as an "alternative" option, not first-line 1

Critical Pitfalls to Avoid

• Never discontinue antibiotics prematurely - complete the full 7-14 day course to prevent relapse 1, 2, 6
• Never use empiric ciprofloxacin for travel-associated cases from South/Southeast Asia - resistance is nearly universal 3, 1, 2
• Never rely solely on Widal test for diagnosis - supplement with blood cultures 6
• Avoid cefixime as first-line therapy due to high failure rates 3, 1, 8

Adverse Effects to Monitor

• Common azithromycin adverse effects include gastrointestinal symptoms: nausea, vomiting, abdominal pain, and diarrhea 1, 2, 6
• Monitor for potential drug interactions with azithromycin, particularly QT-prolonging medications 1, 2
• Ciprofloxacin should be administered at least 2 hours before or 6 hours after antacids, calcium, iron, or zinc products 5

Management of Complications

• Intestinal perforation occurs in 10-15% of patients when illness duration exceeds 2 weeks 3, 1, 2
• Other complications include gastrointestinal bleeding and typhoid encephalopathy 3, 6
• Surgical intervention with simple excision and closure is required for perforation, with success rates up to 88.2% 1, 2
• The addition of steroids may be helpful in severe cases 3

Extensively Drug-Resistant (XDR) Typhoid

• XDR strains have emerged in Pakistan, resistant to chloramphenicol, ampicillin, trimethoprim-sulfamethoxazole, fluoroquinolones, and third-generation cephalosporins 9, 8
• XDR isolates require treatment with azithromycin and/or meropenem 9
• Alternative antimicrobials such as oral carbapenem (tebipenem) need clinical evaluation 9

Prevention Strategies

• Typhoid vaccination is recommended for travelers to endemic areas (Latin America, Asia, Africa) 1, 2
• Two vaccines available: Ty21a oral vaccine and Vi-polysaccharide parenteral vaccine 1
• Vaccination provides only 50-80% protection and does not protect against Salmonella Paratyphi 1, 2
• Hand hygiene and food/water safety precautions remain essential and should not be replaced by vaccination alone 1, 2