Management of Typhoid Fever

First-Line Treatment Options

The American College of Physicians recommends azithromycin 500 mg once daily for 7 days as the first-line treatment for typhoid fever, particularly in areas with high fluoroquinolone resistance, with superior efficacy compared to fluoroquinolones and lower risk of clinical failure (OR 0.48) and shorter hospital stays 1
Azithromycin has a lower risk of relapse (OR 0.09) compared to ceftriaxone and is particularly effective against quinolone-resistant strains 1, 2

For fully susceptible S. typhi, fluoroquinolones (ofloxacin or ciprofloxacin) or alternatives such as chloramphenicol, amoxicillin, or trimethoprim-sulfamethoxazole are recommended 2
For quinolone-resistant strains, azithromycin is the preferred treatment, with alternatives including ceftriaxone or cefixime 1, 2

The Infectious Diseases Society of America recommends considering IV ceftriaxone initially for severe cases, with transition to oral therapy when clinically improved 3
For patients with clinical features of sepsis, broad-spectrum antimicrobial therapy should be started after collection of blood, stool, and urine cultures 3

The Centers for Disease Control and Prevention recommends monitoring for clinical response, with expected fever clearance within 4-5 days of appropriate therapy, and watching for potential drug interactions with azithromycin 1
Common adverse effects of azithromycin include gastrointestinal symptoms: nausea, vomiting, abdominal pain, and diarrhea 1

The World Health Organization notes that typhoid vaccination provides incomplete protection and does not protect against paratyphoid 3

The Centers for Disease Control and Prevention advises against using ciprofloxacin empirically for cases originating from South Asia due to high resistance rates, and recognizes that increasing resistance to fluoroquinolones has been observed, particularly among travelers to South and Southeast Asia 3, 4