What is the recommended treatment for leptospirosis?

Treatment of Leptospirosis

The recommended first-line treatment for leptospirosis is doxycycline 100 mg orally twice daily for 7 days for mild to moderate cases, while severe cases should receive intravenous penicillin G (1.5 million IU every 6 hours), ceftriaxone (1-2 g daily), or ampicillin (1 g every 6 hours) for 7 days. 1

Treatment Algorithm Based on Disease Severity

Mild to Moderate Leptospirosis

• First-line treatment: Doxycycline 100 mg orally twice daily for 7 days 1
• Alternative options (if doxycycline contraindicated):
  • Azithromycin (dosage not specified in guidelines, but appears promising for less severe disease) 2
  • Amoxicillin 500 mg orally three times daily for 7 days 1

Severe Leptospirosis (Weil's syndrome)

• First-line options (any of the following):
  • Penicillin G 1.5 million IU IV every 6 hours for 7 days 1, 3
  • Ceftriaxone 1-2 g IV daily for 7 days 1, 3
  • Ampicillin 1 g IV every 6 hours for 7 days 1

Special Populations

Pregnant Women

• Avoid doxycycline due to potential adverse effects on fetal development
• Recommended options:
  • Penicillin G 1.5 million IU IV every 6 hours for 7 days 1
  • Erythromycin (dosage not specified in guidelines) 1

Evidence Quality and Considerations

The treatment recommendations are primarily based on clinical guidelines from the CDC and WHO as summarized in the Praxis Medical Insights 1. While these represent expert consensus, it's important to note that a recent 2024 Cochrane review indicates that the overall evidence for antibiotic effectiveness in leptospirosis is of very low certainty 4.

Several clinical trials have compared different antibiotics:

• Ceftriaxone (1 g daily) was found to be equally effective as penicillin G (1.5 million U every 6 hours) in a randomized trial of 173 patients with severe leptospirosis, with both having a median fever duration of 3 days and identical mortality rates 3
• Doxycycline was shown to reduce illness duration by approximately 2 days compared to placebo in a small randomized trial 5

Clinical Pearls and Pitfalls

• Early treatment is crucial: Initiate antibiotics as soon as possible after diagnosis to maximize efficacy 1
• Monitor for complications: Severe leptospirosis can lead to multi-organ failure with a mortality rate of 5-15% 1
• Laboratory monitoring: Follow liver and kidney function tests to assess organ involvement and response to treatment 1
• Duration of therapy: Standard duration is 7 days for all antibiotic options 1

Diagnostic Considerations

Diagnosis should be confirmed through:

• Blood cultures (within first 5 days of illness)
• Serological testing showing fourfold or greater increase in agglutination titer
• Demonstration of Leptospira by immunofluorescence 1

The clinical presentation typically includes high fever, severe headache, muscle pain, conjunctival suffusion, and may progress to jaundice, renal failure, and hemorrhagic manifestations in severe cases 1.