Treatment of Leptospirosis
Penicillin and tetracycline antibiotics are the recommended treatment for leptospirosis, with early treatment being essential despite limited evidence of efficacy in established disease. 1
Clinical Presentation and Diagnosis
Leptospirosis presents with a characteristic biphasic course:
- Initial bacteremic phase (4-7 days): Flu-like symptoms
- Immune phase (follows 1-3 days later): Fever, myalgia (especially calves), hepatorenal syndrome, hemorrhage
- Conjunctival suffusion is a suggestive clinical sign
- Severity ranges from mild symptoms to severe illness (Weil's disease) characterized by hemorrhage, jaundice, and hepatorenal failure
Laboratory findings include:
- Proteinuria and hematuria on urinalysis
- Polymorphonuclear leukocytosis
- Thrombocytopenia and anemia (if significant hemorrhage)
- Biochemical evidence of renal failure
- High bilirubin with mild elevation of transaminases
Treatment Algorithm
1. Mild Disease
- Early mild disease is generally self-limiting
- Antibiotics should still be administered upon clinical suspicion due to the non-specific nature of initial investigations 1
- First-line options:
- Doxycycline (can be used safely in children ≥2 years for <2 weeks) 1
- Penicillin
2. Severe Disease (Weil's disease)
- Patients with jaundice and other signs of severe disease may become very ill despite therapy
- May require renal or liver support
- Treatment options:
- Penicillin (intravenous)
- Ceftriaxone or cefotaxime (may be preferred agents based on recent trials) 2
- Doxycycline (alternative)
3. Special Populations
- Children: Doxycycline (for those ≥2 years) or penicillin 1
- Pregnant women: Penicillin (avoid tetracyclines)
Diagnostic Confirmation
While treatment should begin upon clinical suspicion, diagnosis can be confirmed by:
- Serology: IgM titers >1:320 are suggestive (earliest positives appear 6-10 days after symptom onset)
- Convalescent serology >10 days after symptom onset (IgM ELISA and microscopic agglutination test)
- Blood cultures (taken within first 5 days, before antibiotics) - keep at room temperature before dispatch to reference laboratory
Important Considerations
- Person-to-person spread is rare; no restrictions from contact sports are necessary 1
- Risk factors include exposure to contaminated water, recreational sports in lakes/rivers, occupational animal exposure, and flooding 1
- Despite the widespread use of antibiotics, a systematic review showed no benefit for antibiotic treatment based on three trials 1
- However, most infectious disease specialists continue to recommend antibiotics, recognizing that severe disease is likely immunologically mediated 1
Pitfalls and Caveats
- Urine is not a suitable sample for isolation of leptospira 1
- Treatment should not be delayed while awaiting confirmation, as early treatment during the bacteremic phase is thought to be most effective
- Recent meta-analyses have questioned the efficacy of antibiotics on mortality and other outcomes, highlighting the need for better clinical trials 3, 4
- The most recent Cochrane review (2024) found very low-certainty evidence regarding antibiotic efficacy, but clinical practice continues to favor antibiotic treatment 3
Despite the uncertain evidence base, prompt antibiotic therapy remains the standard of care for suspected leptospirosis, with the goal of reducing morbidity and mortality through early intervention.