What is the treatment for leptospirosis?

Treatment of Leptospirosis

For leptospirosis treatment, doxycycline 100 mg orally twice daily for 7 days is recommended for mild to moderate cases, while intravenous penicillin G, ceftriaxone, or ampicillin should be used for severe 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 (dosage not specified in guidelines)
  • Amoxicillin (dosage not specified in guidelines)

Severe Leptospirosis

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

Special Populations

• Pregnant patients: Avoid doxycycline
  • Use penicillin G or erythromycin instead 1

Timing of Treatment

Early treatment is crucial for optimal outcomes. Antibiotics are most effective when started within the first 4-5 days of illness 1. Treatment should begin upon clinical suspicion without waiting for laboratory confirmation, as this can delay critical intervention.

Evidence on Treatment Efficacy

The evidence regarding antibiotic efficacy in leptospirosis shows some conflicting results:

• A randomized trial comparing ceftriaxone (1 g daily) with penicillin G (1.5 million U every 6 hours) found both equally effective for treating severe leptospirosis, with identical median fever resolution time (3 days) and mortality rates 2.

• A double-blind study showed doxycycline reduced illness duration by 2 days compared to placebo and favorably affected symptoms including fever, malaise, headache, and myalgias 3.

• A larger trial comparing cefotaxime, penicillin G, and doxycycline for severe leptospirosis found no significant differences in mortality, time to defervescence, or resolution of laboratory abnormalities 4.

• A meta-analysis from 2021 found no evidence that antibiotics were better than placebo regarding mortality, shortening of fever, or reduction in hospital stay 5. However, this contradicts clinical practice guidelines and earlier studies.

Expected Response to Treatment

Clinical improvement typically occurs within 48-72 hours of appropriate antibiotic therapy, with fever usually resolving within 2 days of starting antibiotics 1. Patients should be monitored for:

• Resolution of fever
• Improvement in symptoms
• Normalization of laboratory parameters (liver and kidney function)

Monitoring and Follow-up

• Follow liver and kidney function tests until normalized
• Monitor for potential complications, particularly in severe cases
• Observe for clinical improvement within 48-72 hours of starting antibiotics

Common Pitfalls and Caveats

1. Delayed treatment: Starting antibiotics late (after 4-5 days) may reduce efficacy and worsen outcomes.

2. Jarisch-Herxheimer reaction: May occur after initiating antibiotic therapy due to rapid lysis of spirochetes.

3. Misdiagnosis: Leptospirosis can mimic other tropical diseases like dengue, malaria, or typhoid fever.

4. Inadequate monitoring: Severe cases require close monitoring for complications including renal failure, pulmonary hemorrhage, and meningitis.

5. Inappropriate antibiotic selection: Using doxycycline in pregnant women or children under 8 years old.

Despite some conflicting evidence in research studies, the most current guidelines strongly recommend antibiotic treatment for all patients with suspected leptospirosis, with the choice of antibiotic and route of administration determined by disease severity.