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, ceftriaxone, or cefotaxime within the first hour without waiting for laboratory confirmation. 1
Disease Classification and Clinical Recognition
Leptospirosis presents in two distinct clinical forms that guide treatment decisions 1:
- Mild to moderate form: Flu-like symptoms including 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
Conjunctival suffusion is a highly suggestive clinical sign that should prompt immediate consideration and treatment of leptospirosis. 1, 2
Treatment Approach by Severity
Mild to Moderate Disease
Start antibiotics as soon as possible based on clinical suspicion alone 1:
- Doxycycline 100 mg orally twice daily for 7 days is highly effective, reducing illness duration by 2 days and favorably affecting fever, malaise, headache, and myalgias 3
- Penicillin is an acceptable alternative, though evidence for superiority over doxycycline is lacking 4, 5
- Azithromycin appears promising for less severe disease 4
The evidence shows doxycycline prevents leptospiruria and has no adverse effects in clinical trials 3. Treatment initiated within the first 4 days of symptoms is most effective; delays beyond this may reduce efficacy 1.
Severe Disease (Weil's Disease)
Initiate intravenous antibiotics within the first hour of recognition, treating as septic shock 1:
- Ceftriaxone or cefotaxime are preferred agents for severe disease 4
- Intravenous penicillin remains an acceptable option 1, 4
- Standard treatment duration is 7 days, extended to 10 days if clinical response is slow 1
Do not delay treatment while awaiting laboratory confirmation, as this increases mortality 1. Patients with severe leptospirosis require ICU admission if they have persistent or worsening tissue hypoperfusion despite initial fluid resuscitation 1.
Critical Management Principles
Timing and Initiation
- Begin antibiotics immediately upon clinical suspicion - treatment effectiveness decreases significantly after 4 days of symptoms 1
- For severe cases, antibiotics must be started within the first hour, following septic shock protocols 1
- Never wait for serological confirmation (IgM titers or culture results) before initiating therapy 1
Duration and Monitoring
- Complete the full 7-day course even with clinical improvement; avoid premature discontinuation 1
- Extend to 10 days in patients with slow clinical response 1
- Reassess antimicrobial regimen daily for potential de-escalation 1
Supportive Care for Severe Cases
Fluid resuscitation is critical, targeting systolic blood pressure >90 mmHg in adults 1:
- Monitor closely for crepitations indicating fluid overload or impaired cardiac function 1
- Continuous observation with frequent clinical examinations is mandatory 1
- Consider source control measures within 12 hours if applicable 1
Important Caveats and Pitfalls
Avoid misdiagnosing leptospirosis as viral hepatitis in patients presenting with fever and jaundice - always consider leptospirosis in the differential, especially with occupational or recreational water exposure 1, 6.
Be aware that evidence for antibiotic superiority over placebo regarding mortality is limited - a 2021 meta-analysis found no statistically significant mortality benefit for penicillin versus placebo (OR 1.65; 95% CI 0.76-3.57) 7. However, antibiotics do reduce illness duration, prevent leptospiruria, and decrease prolonged hospital stays 5, 3.
Jarisch-Herxheimer reactions may occur with antibiotic treatment, though this should not deter appropriate therapy 8.
The majority of Leptospira strains remain sensitive to current antibiotics, making treatment failure due to resistance uncommon 8.