Treatment of Leptospirosis
For mild to moderate leptospirosis, initiate treatment immediately with doxycycline 100 mg orally twice daily or penicillin, and for severe leptospirosis (Weil's disease), start intravenous penicillin G, ceftriaxone, or cefotaxime within the first hour of recognition without waiting for laboratory confirmation. 1
Clinical Classification and Treatment Urgency
Leptospirosis presents in two distinct forms that guide treatment intensity 1:
- Mild to moderate form: Flu-like symptoms with fever (typically ≥39°C), diffuse myalgias (especially calves), headache, and conjunctival suffusion during the 4-7 day septicemic phase 1
- Severe form (Weil's disease): Characterized by hemorrhage, jaundice, and hepato-renal failure, occurring in approximately 5-10% of cases 1
Treatment must begin immediately upon clinical suspicion—do not delay for laboratory confirmation, as mortality increases with delayed antibiotic initiation beyond 4 days of symptoms. 1
Treatment Regimens by Severity
Mild to Moderate Leptospirosis
- Doxycycline 100 mg orally twice daily for 7 days (preferred oral agent)
- Penicillin (alternative oral option)
- Azithromycin (appears promising for less severe disease) 2
The standard treatment duration is 7 days, though extension to 10 days may be necessary in patients with slow clinical response 1.
Severe Leptospirosis (Weil's Disease)
Initiate antibiotics within the first hour of recognition 1:
Preferred intravenous options 2:
- Ceftriaxone (may be preferred agent currently)
- Cefotaxime (acceptable alternative)
- Penicillin G (traditional choice, though cephalosporins may be preferred)
Critical timing consideration: Antibiotic therapy remains effective even when delayed in severe cases, but early administration (within 4 days of symptom onset) is significantly more effective 1, 3.
Supportive Care for Severe Disease
Fluid Resuscitation
- Target systolic blood pressure >90 mmHg in adults with adequate tissue perfusion 1
- Monitor closely for crepitations indicating fluid overload or cardiac dysfunction 1
- Continuous observation is mandatory—septic patients should never be left alone 1
ICU Admission Criteria
- Persistent or worsening tissue hypoperfusion despite initial fluid resuscitation 1
- Development of septic shock or severe sepsis 1
Treatment Monitoring and Adjustment
Daily reassessment is essential 1:
- Evaluate antimicrobial regimen daily for potential de-escalation (though this is less relevant in leptospirosis given the specific pathogen) 1
- Complete the full 7-day course even with clinical improvement—do not discontinue antibiotics prematurely 1
- Consider source control measures within 12 hours if applicable 1
Common Pitfalls to Avoid
Misdiagnosis risk: Leptospirosis with fever and jaundice may be mistaken for viral hepatitis—always consider leptospirosis in the differential diagnosis, especially with exposure history to contaminated water or animals 1.
Delayed treatment: The most critical error is waiting for laboratory confirmation before initiating antibiotics in suspected severe cases, as this directly increases mortality 1.
Inadequate treatment duration: Stopping antibiotics at 5 days or upon clinical improvement rather than completing the full 7-10 day course 1.
Evidence Quality Note
While guidelines clearly recommend antibiotic treatment, the highest quality systematic review evidence (2024 Cochrane review) found very low certainty evidence regarding antibiotic effectiveness on mortality and adverse events 4. However, the 2021 meta-analysis similarly showed no mortality benefit of penicillin over placebo 5. Despite this equivocal research evidence, clinical practice guidelines uniformly recommend immediate antibiotic treatment based on pathophysiology, clinical experience, and the principle of treating a potentially fatal infection 1. The discordance between guideline recommendations and research evidence reflects the difficulty of conducting rigorous trials in this disease with variable clinical course 6, 5.