Typhoid medication
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"typhoid fever"[MeSH Terms] AND "drug therapy"[MeSH Terms]
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Typhoid Fever - Medications & Treatment
Typhoid fever (enteric fever) is caused by Salmonella enterica serotype Typhi (and occasionally S. Paratyphi). Antibiotic treatment is the cornerstone of management, but drug resistance has profoundly changed first-line choices.
First-Line Antibiotics
1. Fluoroquinolones (Fully Susceptible Strains)
- Ciprofloxacin 500 mg twice daily orally (or 15 mg/kg/day) for 5-7 days
- Ofloxacin 15 mg/kg/day for 5-7 days
- Fast-acting, well-tolerated, and relatively inexpensive
- Caveat: Fluoroquinolone resistance is now widespread, especially in travelers returning from South and Southeast Asia. Many strains from this region are nalidixic acid-resistant and fluoroquinolone-nonsusceptible - empiric fluoroquinolone use is NOT recommended in returning travelers from South Asia per the AAP Red Book (2021)
2. Third-Generation Cephalosporins (MDR Strains - Preferred Empiric Therapy)
| Drug | Dose | Route | Duration |
|---|---|---|---|
| Ceftriaxone | 75 mg/kg/day (max 2-4 g/day) | IV/IM | 10-14 days |
| Cefixime | 15-20 mg/kg/day | Oral | 7-14 days |
| Cefotaxime | 200 mg/kg/day | IV | 10-14 days |
Ceftriaxone IV is the preferred empiric choice for moderate-to-severe or multidrug-resistant (MDR) typhoid. Oral cefixime is a suitable step-down for uncomplicated MDR typhoid.
3. Azithromycin (MDR Strains - Oral Option)
- Azithromycin 8-10 mg/kg/day (max 1 g/day) orally for 7 days
- Preferred oral option for uncomplicated MDR typhoid when fluoroquinolones are contraindicated or resistant
- Also used in children and pregnant women where fluoroquinolones are relatively contraindicated
- A 2024 systematic review (PMID: 39623850) confirms azithromycin's clinical efficacy across age groups compared to other antimicrobials
Older/Alternative Agents (Susceptible Strains Only)
These remain effective only when susceptibility is confirmed:
| Drug | Dose | Duration |
|---|---|---|
| Chloramphenicol | 50-75 mg/kg/day | 14-21 days |
| Amoxicillin | 75-100 mg/kg/day | 14 days |
| Ampicillin | 75-100 mg/kg/day | 14 days |
| TMP-SMX | 8-40 mg/kg/day | 14 days |
Chloramphenicol was the historical mainstay from the 1950s, but widespread resistance developed. These drugs are now considered second-tier due to MDR emergence. - Park's Textbook of Preventive & Social Medicine, Table 1
XDR (Extensively Drug-Resistant) Typhoid
Since 2016, Pakistan has been the epicenter of an XDR S. Typhi outbreak. XDR strains are resistant to:
- Ceftriaxone
- Ciprofloxacin
- Ampicillin
- TMP-SMX
Only susceptible to: Azithromycin and Carbapenems
| Scenario | Treatment |
|---|---|
| XDR typhoid, uncomplicated | Azithromycin orally |
| XDR typhoid, severe/complicated | Meropenem or Imipenem IV |
Travelers returning from Pakistan should be specifically assessed for XDR strain. - AAP Red Book 2021, p. 1023
Treatment by Clinical Setting
| Setting | Preferred Regimen |
|---|---|
| Uncomplicated - fully susceptible | Fluoroquinolone PO x 5-7 days |
| Uncomplicated - MDR | Azithromycin PO x 7 days OR Cefixime PO x 7-14 days |
| Moderate-severe or MDR | Ceftriaxone IV x 10-14 days |
| Severe with toxemia | Ceftriaxone IV + Dexamethasone (see below) |
| XDR | Azithromycin PO (mild) or Carbapenem IV (severe) |
| Carrier state | Ampicillin/Amoxicillin 4-6 g/day + Probenecid x 6 weeks; or Ciprofloxacin x 4 weeks |
Adjunctive Therapy
- Dexamethasone (or hydrocortisone 100 mg/day x 3-4 days): Recommended in severely toxic patients with high fever and altered consciousness. It reduces mortality in severe typhoid.
- Supportive care: IV fluids, antipyretics (paracetamol preferred), nutritional support
Special Populations
- Children: Azithromycin or cefixime preferred (fluoroquinolones avoided due to cartilage concerns, though used when no alternative in severe disease)
- Pregnant women: Ceftriaxone is safest; azithromycin is also used; fluoroquinolones and chloramphenicol (3rd trimester) are avoided
- Severe/complicated typhoid: IV ceftriaxone; surgical consultation for intestinal perforation (occurs in ~2% of cases) or uncontrolled hemorrhage
Key Resistance Awareness (2025-2026)
- Fluoroquinolone resistance is rising globally
- In travelers from South Asia (especially Pakistan), do not use fluoroquinolones empirically
- Azithromycin resistance has also emerged in multiple countries where it is used as first-line therapy - per Harrison's Principles of Internal Medicine, 22nd Ed. (2025)
- Always tailor therapy to local susceptibility data and culture results
Sources: Harrison's Principles of Internal Medicine 22E (2025), Sabiston Textbook of Surgery, Tintinalli's Emergency Medicine, Park's Textbook of Preventive & Social Medicine, AAP Red Book 2021, Goodman & Gilman's Pharmacological Basis of Therapeutics
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