Recommended Treatment for Typhoid Fever
The preferred initial treatment for typhoid fever is intravenous ceftriaxone (2g IV daily for adults) for 14 days, especially for patients with unstable clinical conditions or those returning from regions with high fluoroquinolone resistance such as Asia. 1
First-Line Treatment Options
- Intravenous ceftriaxone is the preferred initial treatment for typhoid fever, particularly for patients with severe illness or those returning from regions with high fluoroquinolone resistance 1
- For adults, the recommended dosage is 2g IV daily for 14 days to reduce the risk of relapse 1
- Azithromycin is an effective oral alternative for uncomplicated disease, especially when fluoroquinolone resistance is confirmed 1, 2
- Ciprofloxacin is FDA-approved for typhoid fever (enteric fever) caused by Salmonella typhi, but should be used with caution due to increasing resistance 3
Treatment Selection Based on Regional Resistance Patterns
- In South Asia, fluoroquinolones should be avoided as first-line therapy due to high resistance rates exceeding 70% 1, 2
- When testing isolates for antibiotic sensitivity, ciprofloxacin disc testing alone is unreliable; the organism should also be sensitive to nalidixic acid on disc testing to be considered truly sensitive to fluoroquinolones 1
- Extensively drug-resistant strains have emerged in Pakistan, requiring careful consideration of local resistance patterns 2, 4
Treatment Options for Uncomplicated Typhoid Fever
- For uncomplicated cases, oral azithromycin (20 mg/kg/day, maximum 1g/day) for 7 days has shown excellent efficacy and safety profile 5, 6
- A 5-day course of azithromycin has been found effective for uncomplicated typhoid fever in children and adolescents with fewer relapses compared to ceftriaxone 6
- Cefixime is another oral option but may not perform as well as fluoroquinolones in areas without high resistance 4
Combination Therapy Considerations
- Combination therapy with azithromycin and cefixime is being investigated as a potential treatment option to address increasing antimicrobial resistance 7
- The combination approach targets both intracellular (azithromycin) and extracellular (cefixime) bacterial populations, potentially improving outcomes 7
Monitoring and Complications
- Complications such as gastrointestinal bleeding, intestinal perforation, and typhoid encephalopathy occur in 10-15% of patients, especially if illness duration exceeds 2 weeks 1
- Blood cultures have the highest yield within the first week of symptom onset (sensitivity 40-80%), while stool and urine cultures become positive after the first week 1
- Bone marrow cultures have higher sensitivity than blood cultures but are more invasive 1, 4
Important Clinical Considerations
- Previous vaccination provides incomplete protection against typhoid fever and does not protect against paratyphoid 1
- Treatment choice should be guided by local resistance patterns, with consideration of the route of administration and patient factors 4
- Ciprofloxacin resistance and ceftriaxone resistance are increasingly common, particularly in Pakistan 2