What is the treatment for tularemia?

Treatment of Tularemia

For severe tularemia, streptomycin (15 mg/kg IM every 12 hours) or gentamicin (1.5 mg/kg IV every 8 hours) for 7-14 days is the first-line treatment, while mild cases can be treated with doxycycline (100 mg twice daily) or ciprofloxacin (500 mg twice daily) for 14 days. 1

First-Line Treatment by Disease Severity

Severe or Life-Threatening Tularemia

Aminoglycosides are the drugs of choice for severe disease:

• Streptomycin: 15 mg/kg IM every 12 hours (maximum 1 g per dose) for 7-14 days 1, 2

  • Preferred agent with 97% cure rate and no relapses in historical data 3
  • FDA-approved dosing for tularemia: 1-2 g daily in divided doses for 7-14 days until afebrile for 5-7 days 2

• Gentamicin: 1.5 mg/kg IV every 8 hours (or 3-5 mg/kg/day in divided doses) for 7-14 days 1

  • Acceptable alternative with 86% cure rate, 6% relapse rate, and 8% failure rate 3
  • More readily available than streptomycin and can be given intravenously 4

Critical dosing adjustments:

• Patients over 60 years require reduced aminoglycoside dosing due to significantly increased toxicity risk 1, 2
• All aminoglycoside doses must be adjusted for renal function 4

Mild to Moderate Tularemia

Oral agents are appropriate for less severe presentations:

• Doxycycline: 100 mg PO/IV twice daily for 14 days 1, 4

  • 88% cure rate but 12% relapse rate in historical data 3
  • Minimum 14-day duration required to reduce relapse risk 1

• Ciprofloxacin: 500 mg PO twice daily or 400 mg IV twice daily for 14 days 4

  • Recent US surveillance data (2006-2021) demonstrates fluoroquinolones are independently associated with improved survival 5
  • Effective in both acellular and intracellular models with bactericidal activity 6

Pediatric Dosing

Severe Disease in Children

• Streptomycin: 30 mg/kg/day IM in 2 divided doses (maximum 1 g/day) 1
• Gentamicin: 6 mg/kg/day IV in 3 divided doses 1

Mild Disease in Children

• Doxycycline dosing:

  • Children >45 kg: 100 mg twice daily (adult dosing) 1
  • Children <45 kg: 2.2 mg/kg twice daily 1
  • Avoid in children <8 years due to tooth discoloration risk unless life-threatening infection 1, 4

• Ciprofloxacin: 20 mg/kg PO twice daily or 15 mg/kg IV twice daily 4

Treatment Duration and Monitoring

Duration varies by agent and severity:

• Aminoglycosides: 7-14 days (can stop when afebrile for 5-7 days) 2, 4
• Tetracyclines and fluoroquinolones: Minimum 14 days to reduce relapse risk 1, 4
• Bacteriostatic agents (tetracyclines, chloramphenicol) have higher relapse rates with shorter courses 4, 3

Critical Diagnostic and Safety Considerations

Laboratory safety is paramount:

• F. tularensis poses significant risk for laboratory-acquired infection 1
• Notify laboratory when tularemia is suspected 1
• Organism requires cysteine-supplemented media (thioglycolate broth or charcoal-yeast agar) for culture 4
• Culture should only be attempted in BSL-3 laboratory 4

Preferred diagnostic approach:

• Serologic testing (agglutination tests or ELISA) is the preferred diagnostic method 1, 4
• PCR shows considerable promise for rapid diagnosis 4

Common Pitfalls and Treatment Failures

Beta-lactam antibiotics are completely ineffective and should never be used 1, 4

• Ceftriaxone has demonstrated high failure rates despite favorable in vitro susceptibilities 4

Inadequate treatment duration significantly increases relapse risk:

• Bacteriostatic agents (tetracyclines, chloramphenicol) require full 14-day courses 4, 1
• Chloramphenicol has 77% cure rate but 21% relapse rate 3

Delayed initiation of aminoglycosides may affect outcomes in severe cases 3

Alternative and Emerging Therapies

Recent research has evaluated newer agents, though clinical data remain limited:

• Tigecycline, ketolides (telithromycin, cethromycin), and newer fluoroquinolones (moxifloxacin, gatifloxacin) show promise in vitro and animal models 7
• Fluoroquinolones demonstrate bactericidal activity against intracellular F. tularensis with lower relapse rates compared to doxycycline 6
• US surveillance data (2006-2021) provides supportive evidence that fluoroquinolones are effective for tularemia treatment 5

Special Populations

Pregnancy:

• Aminoglycosides are first-line despite pregnancy category concerns when tularemia is severe 4
• Doxycycline and fluoroquinolones should only be used under exceptional circumstances 4

Bioterrorism exposure:

• Prophylaxis for exposed persons: ciprofloxacin or doxycycline for 14 days 4
• Prolonged treatment may be necessary due to potential in vivo persistence 4