Treatment of Leptospirosis
For mild to moderate leptospirosis, start doxycycline 100 mg orally twice daily or penicillin immediately upon clinical suspicion, and for severe leptospirosis (Weil's disease), initiate intravenous penicillin or ceftriaxone/cefotaxime within the first hour without waiting for laboratory confirmation. 1, 2
Mild to Moderate Leptospirosis
First-line antibiotic options include:
- 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 1, 3
- Penicillin (oral formulation) for 7 days is an alternative first-line agent 1, 4
- Azithromycin (3-day course) appears promising for less severe disease 4
Treatment should be initiated as soon as possible based on clinical suspicion—look for fever with chills, diffuse myalgias (especially calves), headache, conjunctival suffusion (highly suggestive sign), and jaundice 1. Early treatment (within 4 days of symptom onset) is critical, as delayed therapy beyond this window may be less effective 2.
Severe Leptospirosis (Weil's Disease)
Severe disease is characterized by hemorrhage, jaundice, and hepato-renal failure, occurring in approximately 5-10% of infected individuals 1. Neurological manifestations including status epilepticus indicate CNS involvement during the immune phase 2.
Immediate antibiotic management:
- Intravenous penicillin is the preferred agent for severe disease with neurological involvement 2
- Ceftriaxone or cefotaxime are acceptable alternatives and may be preferred agents due to favorable safety profiles 4
- Standard treatment duration is 7 days, but extend to 10 days in patients with slow clinical response 2
- Start antibiotics within the first hour of recognition of septic shock or severe sepsis—do not delay for laboratory confirmation, as this increases mortality 2
Critical Management Principles
Timing is everything: Treatment initiated after 4 days of symptoms may be substantially less effective 2. The septicemic/bacteremic phase lasts only 4-7 days, making early intervention crucial 1.
Do not wait for confirmatory testing before starting antibiotics in suspected severe cases. IgM titers >1:320 are suggestive of leptospirosis, but titers of 1:80-1:160 are consistent with early infection 1. Blood cultures are most useful if obtained within the first 5 days before antibiotics 1.
Complete the full antibiotic course even with clinical improvement—discontinuing antibiotics too early should be avoided 2.
Supportive Care for Severe Disease
Fluid resuscitation targeting systolic blood pressure >90 mmHg in adults with adequate tissue perfusion as the principal endpoint 1. Monitor for crepitations indicating fluid overload during resuscitation 1.
Monitor and manage complications including:
- Renal function (proteinuria and hematuria are common) 1, 2
- Hepatic function (elevated bilirubin with mild transaminase elevation) 1, 2
- Hematologic parameters and bleeding risk 2
- Seizure management with antiepileptic therapy as indicated 2
ICU admission is required for patients with persistent or worsening tissue hypoperfusion despite initial fluid resuscitation 1.
Common Pitfalls
Misdiagnosis as viral hepatitis: Leptospirosis may be mistaken for viral hepatitis in patients presenting with fever and jaundice—always consider leptospirosis in the differential, especially with occupational or recreational water exposure 1.
Inadequate treatment duration: The evidence suggests 7 days as standard, but clinical response should guide extension to 10 days if needed 2.
Delayed antibiotic initiation: Every hour counts in severe disease—the recommendation to start within the first hour of recognition is a Grade 1B/1C recommendation from critical care guidelines 2.