Leptospirosis Treatment Regimen
For mild to moderate leptospirosis, initiate doxycycline 100 mg orally twice daily for 7 days; for severe disease (Weil's disease with jaundice, renal failure, or hemorrhage), administer intravenous ceftriaxone 1 g daily for 7 days or penicillin G 1.5 million units every 6 hours for 7 days. 1, 2, 3
Disease Severity Assessment and Treatment Initiation
Treatment should begin immediately upon clinical suspicion without waiting for confirmatory testing, given the non-specific nature of initial laboratory findings and the potential for rapid deterioration. 1
Mild to Moderate Disease (Outpatient)
- Doxycycline 100 mg orally twice daily for 7 days is the standard therapy for early leptospirosis, reducing illness duration by approximately 2 days and favorably affecting fever, malaise, headache, and myalgias. 4, 5
- This regimen is effective during the bacteremic phase (first 4-7 days of illness) and prevents leptospiruria. 4
- For adults, the FDA-approved dosing is 200 mg on day 1 (100 mg every 12 hours), followed by 100 mg daily, though the twice-daily regimen is more commonly used in practice. 6
Severe Disease (Weil's Disease - Hospitalized Patients)
Ceftriaxone 1 g intravenously daily for 7 days is now preferred over penicillin due to once-daily administration convenience and broader antimicrobial spectrum. 2, 3
Alternative regimens for severe disease include:
- Penicillin G 1.5 million units intravenously every 6 hours for 7 days (traditional standard of care). 2, 3
- Cefotaxime (dosing comparable to ceftriaxone). 3
- Doxycycline 100 mg intravenously or orally twice daily for 7 days is equally effective as penicillin or ceftriaxone in severe disease. 3
A randomized trial of 173 patients demonstrated equivalent efficacy between ceftriaxone and penicillin G, with median fever duration of 3 days in both groups and identical mortality rates (5.7% vs 5.8%). 2 A larger trial of 540 patients confirmed no significant differences in mortality, defervescence, or laboratory resolution among cefotaxime, penicillin G, and doxycycline. 3
Pediatric Dosing
For children over 8 years of age, doxycycline 2 mg/lb (4.4 mg/kg) divided into two doses on day 1, followed by 1 mg/lb (2.2 mg/kg) daily (or divided twice daily) for severe infections. 6
- For children weighing >100 lbs, use adult dosing. 6
- Penicillin or cephalosporins are preferred for children under 8 years to avoid tetracycline-related dental staining. 1
Critical Clinical Considerations
Severe leptospirosis is likely immunologically mediated, which explains why antibiotics may not dramatically alter outcomes once organ dysfunction develops, though they remain recommended by infectious disease specialists. 1
Patients with Weil's disease (jaundice, hepatorenal syndrome, hemorrhage) may deteriorate despite appropriate antibiotic therapy and require:
- Renal replacement therapy for acute kidney injury. 1
- Liver support for hepatic dysfunction. 1
- Management of hemorrhagic complications (due to capillary fragility, not coagulopathy). 1
Common Pitfalls to Avoid
- Do not delay treatment waiting for serological confirmation, as IgM antibodies may not appear until 6-10 days after symptom onset. 1
- Do not use urine samples for culture, as they are not suitable for leptospira isolation; blood cultures (taken within first 5 days, kept at room temperature) are preferred. 1
- Do not assume normal coagulation studies exclude bleeding risk, as hemorrhage results from capillary fragility rather than coagulopathy. 1
- For patients in rickettsial co-endemic areas (e.g., Thailand), doxycycline provides superior coverage compared to penicillin, as it treats both leptospirosis and rickettsial infections. 3
Alternative Agents
Azithromycin shows promise for less severe disease, though evidence is limited compared to doxycycline. 7
Fluoroquinolones (e.g., ciprofloxacin) may be considered, particularly for leptospiral uveitis as adjunctive therapy, though adequate human trials are lacking for primary treatment. 7, 5