What is the treatment for leptospirosis?

Treatment of Leptospirosis

For mild to moderate leptospirosis, start doxycycline 100 mg orally twice daily or penicillin as soon as possible; for severe leptospirosis, initiate intravenous penicillin or ceftriaxone within 1 hour of recognition without waiting for laboratory confirmation. 1

Classification and Treatment Approach

Leptospirosis presents in two distinct clinical forms that guide treatment decisions 1:

• Mild to moderate form: Flu-like symptoms, most common presentation
• Severe form (Weil's disease): Hemorrhage, jaundice, hepato-renal failure, occurs in 5-10% of cases

Treatment for Mild to Moderate Leptospirosis

Antibiotic selection should be initiated as soon as the diagnosis is suspected 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 2
• Penicillin is an acceptable alternative, though it has long been considered the traditional treatment of choice 3
• Azithromycin appears promising for less severe disease 3

Key consideration: Doxycycline prevents leptospiruria and has demonstrated clear clinical benefit in randomized trials 2. However, tetracyclines including doxycycline are contraindicated in children under 8 years due to risk of permanent tooth discoloration and enamel hypoplasia 4.

Treatment for Severe Leptospirosis (Weil's Disease)

Immediate antibiotic administration is critical - treatment must begin within 1 hour of recognizing severe sepsis or septic shock, as each hour of delay increases mortality 1:

First-line options:

• Intravenous penicillin (1.5 million units every 6 hours for 7 days) 5
• Ceftriaxone (1 g IV daily for 7 days) - equally effective to penicillin with the advantage of once-daily dosing and extended spectrum coverage 5
• Cefotaxime is also an acceptable agent 3

Treatment duration and monitoring:

• Standard course: 7 days, but may extend to 10 days in patients with slow clinical response 1
• Do not wait for laboratory confirmation before starting antibiotics 1
• Obtain blood cultures before antibiotics if this causes no significant delay (<45 minutes), ideally within the first 5 days of illness 1
• Reassess antimicrobial regimen daily for potential de-escalation 1

Critical Management Pitfalls to Avoid

Timing errors are the most dangerous mistakes 1:

• Early antibiotic administration initiated after 4 days of symptoms may be less effective
• Never discontinue antibiotics too early - complete the full course even with clinical improvement
• Never delay treatment while waiting for serological confirmation

Misdiagnosis risk: Leptospirosis may be misdiagnosed as viral hepatitis in patients presenting with fever and jaundice 1. Always consider leptospirosis in the differential diagnosis, especially with:

• High-risk exposure history (recreational water sports in fresh water, occupational exposure to animals, recent flooding, contact with rats/dogs/cattle) 1
• Conjunctival suffusion (a highly suggestive sign) 1
• Diffuse myalgias, especially in the calves 1

Supportive Care for Severe Cases

Fluid resuscitation is essential 1:

• Target systolic blood pressure >90 mmHg in adults
• Monitor for crepitations indicating fluid overload or impaired cardiac function
• Patients with persistent tissue hypoperfusion despite initial fluid resuscitation require ICU admission 1

Continuous monitoring is mandatory - septic patients should never be left alone and require frequent clinical examinations 1.

Evidence Quality Note

While guidelines strongly recommend antibiotic treatment, a 2021 meta-analysis found no statistically significant effect of penicillin on mortality compared to placebo 6. However, this analysis was limited by the small number of trials (most recent from 2007) and methodological concerns 7. In clinical practice, the consensus remains to treat with antibiotics given the potential severity of disease, favorable safety profile, and individual trial evidence showing clinical benefit 1, 2.