Management of Typhoid Fever (Enteric Fever)

1. General Principles

Typhoid fever (caused by Salmonella enterica serotype Typhi) carries an overall case-fatality rate of ~2.5%, rising to 4.5% among hospitalized patients. Prompt antibiotic therapy reduces this dramatically - untreated, mortality is 10-20%. Management is guided by:

Antibiotic susceptibility pattern of the strain
Severity of illness
Presence of complications
Patient population (adult vs child, pregnancy, immunocompromised)

2. Antibiotic Therapy

A. Uncomplicated Typhoid - By Susceptibility Pattern

Based on Park's Textbook of Preventive and Social Medicine and Harrison's Principles (22nd ed., 2025):

Susceptibility	Optimal Antibiotic	Dose (mg/kg/day)	Duration	Alternatives
Fully sensitive	Fluoroquinolone (ciprofloxacin or ofloxacin)	15	5-7 days	Chloramphenicol 50-75 mg/kg × 14-21 d; Amoxicillin 75-100 mg/kg × 14 d; TMP-SMX 8-40 mg/kg × 14 d
Multidrug resistant (MDR)	Fluoroquinolone OR Cefixime	15 / 15-20	5-7 d / 7-14 d	Azithromycin 8-10 mg/kg × 7 d; Cefixime 15-20 mg/kg × 7-14 d
Quinolone-resistant	Azithromycin OR Ceftriaxone	8-10 / 75	7 d / 10-14 d	Cefixime 20 mg/kg × 7-14 d

Key point on fluoroquinolone resistance: Resistance is rising sharply - especially in travelers from South Asia (India, Pakistan) and Southeast Asia, linked to nalidixic acid-resistant strains. Fluoroquinolones should not be used empirically in these regions. Azithromycin or third-generation cephalosporins are preferred.

A 2024 systematic review (PMID 39623850) found oral azithromycin to be clinically effective vs other antimicrobials across all age groups, comparable to ceftriaxone in uncomplicated disease.

B. Standard Adult Doses (Oral)

Ciprofloxacin 500 mg twice daily × 7-10 days (sensitive strains)
Ofloxacin 400 mg twice daily × 7-10 days
Azithromycin 1 g daily × 5-7 days (quinolone-resistant areas)
Cefixime 15-20 mg/kg/day × 7-14 days (MDR strains)
Ceftriaxone 2 g IV once or twice daily × 10-14 days (severe or parenteral)

Ampicillin, TMP-SMX, and chloramphenicol are now unreliable due to widespread resistance.

Sleisenger and Fordtran's Gastrointestinal and Liver Disease, p. 2197
Harrison's Principles of Internal Medicine 22E, p. 1360

3. Severe Typhoid Fever

Severe disease features: high fever with altered sensorium, shock, GI perforation, severe hemorrhage, or typhoid encephalitis/meningitis.

Management:

Parenteral antibiotics - Ceftriaxone 2 g IV daily × 10-14 days is preferred
Add dexamethasone in severe cases with delirium, obtundation, stupor, coma, or shock:
- Dose: 8 mg/kg × 1 loading dose, then 1 mg/kg every 6 hours × 48 hours (total 3 days)
- This has been shown to reduce mortality in severe typhoid
IV fluid resuscitation
Blood transfusion if hemorrhage causes significant anemia
Broad-spectrum antibiotic coverage broadened for polymicrobial peritonitis if perforation occurs

Tintinalli's Emergency Medicine, p. 3387
Sleisenger and Fordtran's GI Disease, p. 2198

4. Complications and Their Management

Complication	Timing	Management
Intestinal perforation (1%)	3rd-4th week	Emergency surgery + broadened antibiotics for peritonitis
GI hemorrhage (6%)	3rd-4th week	Fluid resuscitation, blood transfusion, possibly bowel resection
Typhoid encephalitis / meningitis	Any time	Ceftriaxone IV + dexamethasone
Relapse	2-6 weeks post-recovery	Repeat antibiotic course (same agent usually effective)
Carrier state	>12 months shedding	See below

Harrison's Principles 22E

5. Carrier State Management

Chronic carriers (biliary carriers >1 year) are the ultimate reservoir. Treatment options:

Ampicillin or Amoxicillin 4-6 g/day + Probenecid 2 g/day × 6 weeks (bile-concentrated; ~70% eradication)
Cholecystectomy + concurrent ampicillin: cure rate up to 80% (best approach for gallbladder carriers)
Urinary carriers: antibiotic treatment; refractory cases may need nephrectomy
Carriers must be restricted from food handling and kept under surveillance
Park's Textbook of Preventive and Social Medicine, p. 279

6. Supportive Care

Adequate oral or IV hydration
Antipyretics (paracetamol preferred; avoid NSAIDs if bleeding risk)
Nutritional support - soft, easily digestible diet
Monitoring for complications (daily abdominal exam, watch for signs of peritonism)
Strict enteric precautions and isolation of stool/urine

7. Special Situations

Situation	Preferred Agent
Pregnancy	Ceftriaxone (fluoroquinolones and chloramphenicol avoided)
Children	Cefixime or azithromycin; ceftriaxone for severe disease
MDR / XDR typhoid	Azithromycin (oral) or ceftriaxone/meropenem (parenteral)
Typhoid with HIV	Standard antibiotics; higher relapse risk - consider longer course

8. Post-treatment Follow-up

Relapse occurs in 5-10% of cases, typically 2-3 weeks after apparent recovery - treat with a repeat antibiotic course
Stool cultures at 1 and 3 months post-treatment to confirm clearance, especially in food handlers
Vaccination of close contacts and household members

Summary Algorithm

Typhoid suspected (fever >5 days + travel history)
        ↓
Blood culture + susceptibility testing
        ↓
Uncomplicated?          Severe (altered consciousness/shock/perforation)?
    ↓                                    ↓
Check susceptibility            Ceftriaxone IV + Dexamethasone
    ↓
Sensitive strain → Fluoroquinolone (if NOT South/SE Asia)
MDR → Cefixime or Fluoroquinolone
Quinolone-resistant → Azithromycin or Ceftriaxone

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