Treatment of Tularemia
For severe tularemia, streptomycin (15 mg/kg IM every 12 hours) or gentamicin (1.5 mg/kg IV every 8 hours) should be administered for 7-14 days; for mild cases, doxycycline (100 mg twice daily) or tetracycline (500 mg four times daily) is recommended. 1
Treatment Algorithm Based on Disease Severity
Severe Tularemia (Pneumonic, Typhoidal, or Systemically Ill Patients)
First-line therapy:
- Streptomycin 15 mg/kg IM every 12 hours (maximum 2 g/day) for 7-14 days 1, 2
- Alternative: Gentamicin 1.5 mg/kg IV every 8 hours (or 3-5 mg/kg/day in divided doses) for 7-14 days 1
The FDA-approved dosing for tularemia specifically indicates 1-2 g of streptomycin daily in divided doses for 7-14 days until the patient is afebrile for 5-7 days 2. Streptomycin remains the gold standard with a 97% cure rate and no relapses in historical data 3. Gentamicin shows an 86% cure rate with a 6% relapse rate, making it an acceptable alternative when streptomycin is unavailable 3.
Important consideration: Patients over 60 years should receive reduced aminoglycoside dosing due to increased toxicity risk 1, 2. Aminoglycoside doses must be adjusted for renal function 1.
Mild to Moderate Tularemia (Ulceroglandular, Glandular Forms)
First-line oral therapy:
- Doxycycline 100 mg twice daily for 14 days 1, 4, 5
- Alternative: Tetracycline 500 mg four times daily for 14 days 1
Doxycycline is FDA-approved for tularemia treatment and provides effective coverage against Francisella tularensis 5. However, tetracyclines have an 88% cure rate with a 12% relapse rate, which is higher than aminoglycosides 3. The relapse risk is particularly elevated when treatment duration is less than 7-10 days 1.
Fluoroquinolones as alternative agents:
- Ciprofloxacin 750 mg twice daily or levofloxacin 500-750 mg daily for 14 days 1, 6
- Recent evidence suggests fluoroquinolones may be more effective than doxycycline for mild infections, with excellent clinical response and no relapses in reported cases 7, 6
- All 10 reported cases treated with fluoroquinolones showed favorable outcomes without relapse 6
Pediatric Dosing
Severe disease:
- Streptomycin 30 mg/kg/day IM in 2 divided doses (maximum 1 g) 1
- Gentamicin 6 mg/kg/day IV in 3 divided doses 1
Mild disease:
- Doxycycline dosing: Patients >45 kg receive adult dosing; patients <45 kg receive 2.2 mg/kg twice daily 4
- Note: Doxycycline should generally be avoided in children <8 years due to tooth discoloration risk, but may be used for life-threatening infections when benefits outweigh risks 4
Critical Diagnostic and Safety Considerations
Laboratory notification is mandatory: Always notify the microbiology laboratory when tularemia is suspected, as F. tularensis poses significant risk for laboratory-acquired infection 1. Serologic testing (agglutination tests or ELISA) is the preferred diagnostic method 1.
Common Pitfalls and Treatment Failures
Beta-lactam antibiotics are ineffective: Ceftriaxone and other beta-lactams have high failure rates despite favorable in vitro susceptibilities and should never be used 1, 3, 7.
Inadequate treatment duration: Treatment courses shorter than 7-10 days, particularly with bacteriostatic agents like tetracyclines, significantly increase relapse rates 1, 3. Many patients require 14 days of therapy, especially when treatment is initiated more than 2-3 weeks after disease onset 7.
Gentamicin treatment failures: Recent pediatric data demonstrates that gentamicin may fail in oropharyngeal tularemia, with successful salvage using streptomycin for 14 days 8. The 7-day gentamicin course may be insufficient, and delayed initiation may affect outcomes in severe cases 3.
Suppurative lymphadenopathy: Approximately 30% of patients develop suppurative lymph nodes requiring surgical drainage or excision in addition to antibiotics, particularly when antibiotic therapy is delayed 7. High rates of treatment failure and relapse occur regardless of antibiotic choice when treatment begins more than 2-3 weeks after symptom onset 7.