What is the recommended treatment for leptospirosis?

Treatment of Leptospirosis

For mild to moderate leptospirosis, start doxycycline 100 mg orally twice daily for 7 days or penicillin; for severe leptospirosis (Weil's disease), initiate intravenous penicillin G 1.5 million units every 6 hours or ceftriaxone 1 g daily for 7 days immediately upon clinical suspicion without waiting for laboratory confirmation. 1, 2

Disease Classification and Clinical Recognition

Leptospirosis presents in two distinct forms that determine treatment approach:

• Mild to moderate form: Flu-like symptoms with fever (usually ≥39°C), diffuse myalgias (especially calves), headache, and conjunctival suffusion (a highly suggestive sign) 1
• Severe form (Weil's disease): Characterized by hemorrhage, jaundice, and hepato-renal failure, occurring in 5-10% of infected individuals 1, 2

The septicemic/bacteremic phase lasts 4-7 days and represents the optimal window for antibiotic intervention 1, 3

Treatment Algorithm by Severity

Mild to Moderate Disease

First-line options:

• Doxycycline 100 mg orally twice daily for 7 days - reduces illness duration by 2 days and favorably affects fever, malaise, headache, and myalgias 4
• Penicillin oral formulation - effective during the bacteremic phase 2
• Azithromycin - appears promising for less severe disease 5

Critical caveat: In children under 8 years, use penicillin or amoxicillin instead of doxycycline due to potential effects on bone and teeth development 2

Severe Disease (Weil's Disease)

Immediate antibiotic initiation is mandatory:

• Start antibiotics within the first hour of recognition, as each hour of delay increases mortality 1
• Do not wait for laboratory confirmation - treatment must begin on clinical suspicion alone 1, 2

First-line options (equally effective):

• Penicillin G 1.5 million units IV every 6 hours for 7 days 6
• Ceftriaxone 1 g IV daily for 7 days - offers once-daily dosing advantage and extended spectrum coverage 6
• Cefotaxime - acceptable alternative agent 5

The standard course is 7 days, but may extend to 10 days in patients with slow clinical response 1

Critical Timing Considerations

The window for antibiotic effectiveness is narrow:

• Treatment initiated after 4 days of symptoms may be less effective 1
• Antibiotics work best during the bacteremic phase (first 4-7 days) 1, 3
• The severe phase is immune-mediated, so antibiotic benefit may be limited once Weil's disease develops 2

Blood cultures should be obtained:

• Within the first 5 days of illness, before antibiotics if this causes no significant delay (<45 minutes) 1

Hospitalization Criteria

• Moderate leptospirosis with systemic signs requires hospitalization even without criteria for severe disease 1
• Severe leptospirosis requires ICU admission if persistent or worsening tissue hypoperfusion despite initial fluid resuscitation 1

Supportive Care for Severe Disease

Fluid resuscitation:

• Target systolic blood pressure >90 mmHg in adults with adequate tissue perfusion 1
• Monitor for crepitations indicating fluid overload or impaired cardiac function 1
• Continuous observation required - septic patients should never be left alone 1

Additional management:

• Reassess antimicrobial regimen daily for potential de-escalation 1
• Consider source control measures within 12 hours if applicable 1
• Complete the full antibiotic course even with clinical improvement 1

Common Pitfalls to Avoid

Diagnostic confusion:

• Leptospirosis may be misdiagnosed as viral hepatitis in patients presenting with fever and jaundice - maintain high clinical suspicion 1

Treatment errors:

• Do not discontinue antibiotics early despite clinical improvement 1
• Do not delay treatment waiting for serological confirmation (IgM titers >1:320 are suggestive but convalescent serology >10 days may be needed) 1
• Do not use doxycycline in children under 8 years 2

Clinical deterioration:

• Patients with classic Weil's disease (jaundice) can deteriorate rapidly despite appropriate antibiotics and may require renal or hepatic support 2