What is the recommended dose and duration of treatment for leptospirosis, including prophylactic treatment?

Treatment and Prophylaxis of Leptospirosis

Treatment of Mild to Moderate Leptospirosis

For mild to moderate leptospirosis, initiate doxycycline 100 mg orally twice daily for 7 days immediately upon clinical suspicion without waiting for laboratory confirmation. 1, 2

• Doxycycline is the preferred oral agent for adults and children over 8 years of age at 100 mg twice daily for 7 days 1, 2, 3
• For children weighing less than 100 pounds (45 kg): administer 2 mg/lb (2.2 mg/kg) divided into two doses on day 1, followed by 1 mg/lb daily as a single dose or divided into two doses 3
• Alternative oral regimen: Penicillin V or amoxicillin can be used, particularly for children under 8 years where doxycycline should be avoided due to effects on bone and teeth development 2, 4
• Treatment duration may be extended to 10 days in patients with slow clinical response 2

Treatment of Severe Leptospirosis

For severe leptospirosis with jaundice, renal failure, hemorrhage, or respiratory compromise, initiate intravenous penicillin G 1.5 million units every 6 hours for 7 days immediately. 1, 2

• Penicillin G intravenous is the standard treatment: 1.5 million units every 6 hours for 7 days 1, 5
• Ceftriaxone 1 gram IV daily for 7 days is equally effective and offers the advantage of once-daily dosing with broader spectrum coverage 5, 6
• Antibiotics must be started within the first hour of recognition of severe sepsis or septic shock 2
• Treatment initiated after 4 days of symptoms may be less effective, as the severe phase is immunologically mediated 2, 4
• Duration should be 7 days standard, extended to 10 days if clinical response is slow 2

Critical Management Points for Severe Disease

• Do not delay antibiotic initiation while waiting for laboratory confirmation—this increases mortality 2
• Patients with Weil's disease (jaundice, renal failure, hemorrhage) require ICU admission and may deteriorate despite antibiotics 2, 4
• Fluid resuscitation targeting systolic blood pressure >90 mmHg in adults is essential 2
• Monitor for fluid overload with frequent clinical examinations 2

Treatment Algorithm Based on Severity

Mild disease (fever, myalgias, headache, no organ dysfunction):

• Doxycycline 100 mg PO twice daily × 7 days 1, 2
• Alternative: Penicillin V orally 2, 4

Severe disease (jaundice, renal failure, hemorrhage, respiratory compromise):

• Penicillin G 1.5 million units IV every 6 hours × 7 days 1, 5
• Alternative: Ceftriaxone 1 gram IV daily × 7 days 5, 6
• Extend to 10 days if slow response 2

Neurological involvement (meningitis, spinal involvement):

• Penicillin G 1.5 million units IV every 6 hours × 7-10 days 1
• Perform lumbar puncture for CSF analysis 1
• Obtain urgent MRI for spinal cord involvement 1

Prophylactic Treatment

For high-risk exposure in endemic areas (such as military personnel or during floods), administer doxycycline 200 mg as a single dose at the time of exposure. 7, 8

• Weekly doxycycline 200 mg does NOT prevent symptomatic leptospirosis and should not be used 7, 8
• Single-dose doxycycline 200 mg at time of flood water exposure showed benefit in preventing symptomatic infection (OR 0.23; 95% CI 0.07-0.77) 8
• For prolonged exposure in endemic areas: doxycycline 100 mg daily starting 1-2 days before exposure and continuing throughout exposure 3, 7
• This regimen reduced symptomatic infection in soldiers training in endemic areas (risk difference -4.1%, NNT 24) 7

Prophylaxis Dosing

Adults: 100 mg daily or 200 mg single dose at exposure 3, 7, 8

Children over 8 years: 2 mg/kg daily up to adult dose 3

Common Pitfalls and Caveats

• Do not use doxycycline in children under 8 years—use penicillin or amoxicillin instead 4
• Do not wait for serological confirmation to start treatment—early bacteremic phase (first 4-7 days) is when antibiotics are most effective 1, 2
• Do not discontinue antibiotics early even with clinical improvement—complete the full 7-day course 2
• Antibiotics have limited benefit in the late immunologic phase (after day 7), but should still be given 2, 4
• Weekly doxycycline prophylaxis is ineffective; only single-dose or daily regimens work 7, 8

Evidence Quality Note

The most recent meta-analysis 8 from 2021 found no mortality benefit from penicillin versus placebo, though this conflicts with older guidelines. However, the guideline evidence 1, 2 from 2025 and the practical reality that severe leptospirosis carries 5-10% mortality supports antibiotic use. The single high-quality RCT 5 from 2003 demonstrated equal efficacy between ceftriaxone and penicillin G for severe disease.