What is the recommended treatment for leptospirosis?

Treatment of Leptospirosis

Doxycycline is the recommended first-line treatment for leptospirosis, with a dosage of 100 mg orally twice daily for 7 days for mild to moderate cases 1.

Treatment Algorithm Based on Disease Severity

Mild to Moderate Leptospirosis

• First-line therapy: Doxycycline 100 mg orally twice daily for 7 days 1
• Alternative options (if doxycycline contraindicated):
  • Azithromycin (promising for less severe disease) 2
  • Amoxicillin 500 mg PO/IV q8h 2

Severe Leptospirosis (requiring hospitalization)

• First-line therapy:
  • Intravenous penicillin G 1.5 million IU every 6 hours for 7 days 1, 3
  • OR Ceftriaxone 1 g IV daily for 7 days 1, 3
• Alternative options:
  • Ampicillin 1 g IV every 6 hours for 7 days 1
  • Cefotaxime 1-2 g IV daily for 7 days 1

Special Populations

Pregnant Patients

• Avoid doxycycline
• Recommended treatment:
  • Penicillin G 1.5 million IU IV every 6 hours for 7 days 1
  • OR Erythromycin (dosage based on weight) 1

Clinical Evidence and Rationale

The Centers for Disease Control and Prevention and the World Health Organization recommend doxycycline as the drug of choice for leptospirosis 1. This recommendation is supported by clinical evidence showing that doxycycline reduces the duration of illness by approximately 2 days and favorably affects symptoms including fever, malaise, headache, and myalgias 4.

For severe cases requiring hospitalization, both penicillin G and ceftriaxone have demonstrated equal efficacy. A randomized trial comparing these two antibiotics showed no significant differences in time to fever resolution (median of 3 days for both groups) or mortality rates 3. However, ceftriaxone offers the advantage of once-daily administration and a broader spectrum of activity against potential bacterial co-infections 3.

Treatment Monitoring

• Monitor for clinical improvement within 24-48 hours after initiating therapy
• Assess for resolution of fever, which typically occurs within a median of 3 days 3
• Follow laboratory parameters including renal and hepatic function tests in severe cases

Common Pitfalls to Avoid

1. Delayed treatment: Early antibiotic therapy is crucial for reducing disease severity and preventing complications
2. Inadequate dosing: Ensure appropriate weight-based dosing, particularly for children and pregnant women
3. Jarisch-Herxheimer reaction: Be aware that antibiotic treatment may precipitate this reaction, characterized by fever, chills, and hypotension shortly after initiating therapy
4. Failure to recognize severe disease: Promptly identify patients requiring IV antibiotics and supportive care

Evidence Quality Considerations

While antibiotics are widely used for leptospirosis, a recent Cochrane review indicates that the overall quality of evidence supporting antibiotic therapy is very low 5. Nevertheless, clinical practice continues to favor antibiotic treatment based on observational data, pathophysiological rationale, and the potential benefits outweighing the risks, particularly in severe cases.

The most recent evidence suggests that penicillin may provide more benefit than harm 6, and ceftriaxone offers comparable efficacy with the convenience of once-daily dosing 3.