What is the recommended treatment for leptospirosis?

Treatment of Leptospirosis

For leptospirosis, initiate antibiotic therapy immediately upon clinical suspicion without waiting for laboratory confirmation, using penicillin, doxycycline, or third-generation cephalosporins (ceftriaxone or cefotaxime) depending on disease severity. 1, 2

Mild to Moderate Disease (Outpatient/Early Presentation)

Recommended antibiotics for mild to moderate leptospirosis:

• Doxycycline 100 mg orally twice daily for 7 days is effective and reduces illness duration by approximately 2 days, favorably affecting fever, malaise, headache, and myalgias 1, 3
• Penicillin (oral formulation) is an acceptable alternative, though has been traditionally considered first-line 1, 4, 5
• Azithromycin appears promising for less severe disease, though evidence is more limited 4

Critical timing consideration: Treatment initiated within the first 4 days of symptoms is most effective; delayed treatment beyond this window may be less beneficial 1

Severe Disease (Hospitalized/Weil's Disease)

For severe leptospirosis with jaundice, hemorrhage, or hepato-renal failure, use intravenous antibiotics:

• Ceftriaxone 1 g IV daily for 7 days is equally effective as penicillin with the advantage of once-daily dosing and broader spectrum coverage 6
• Cefotaxime IV is also an acceptable agent with similar efficacy 4, 7
• Penicillin G 1.5 million units IV every 6 hours for 7 days remains a standard option 6, 7

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

Critical Management Principles

Timing is paramount:

• Antibiotics must be started within the first hour of recognizing severe disease or septic shock 1
• Do not delay treatment while awaiting serologic confirmation, as IgM titers only become positive 6-10 days after symptom onset 2
• Blood cultures are only useful if obtained within the first 5 days before antibiotic administration 1, 2

Supportive care for severe disease:

• Fluid resuscitation targeting systolic blood pressure >90 mmHg in adults 1
• Monitor closely for fluid overload with continuous observation 1
• ICU admission may be required for persistent hypoperfusion despite initial resuscitation 1

Special Populations

Children under 8 years:

• Doxycycline is contraindicated due to risk of permanent tooth discoloration and enamel hypoplasia 2
• Use penicillin or cephalosporins instead 2

Pregnant women:

• Avoid tetracyclines (doxycycline) 2
• Use penicillin or cephalosporins 2

Common Pitfalls to Avoid

• Never delay treatment waiting for laboratory confirmation - the non-specific nature of initial investigations and potential for rapid progression to severe disease make empiric treatment essential 1, 2
• Do not assume mild symptoms will remain mild - approximately 5-10% progress to severe Weil's disease with hemorrhage, jaundice, and renal failure 1
• Do not discontinue antibiotics prematurely - complete the full 7-day course even with clinical improvement 1
• Do not miss the diagnosis - leptospirosis may be misdiagnosed as viral hepatitis in patients presenting with fever and jaundice 1

Diagnostic Clues Supporting Clinical Suspicion

Key clinical features that should trigger immediate empiric treatment:

• Conjunctival suffusion (distinctive finding highly suggestive of leptospirosis) 1, 2
• Biphasic illness pattern with initial bacteremic phase lasting 4-7 days 2
• High fever (≥39°C) with severe calf myalgias 1
• Recent exposure to contaminated water, especially flood water or occupational/recreational freshwater contact 2, 8
• Laboratory findings: proteinuria, hematuria, leukocytosis, elevated bilirubin with mild transaminase elevation 1