What antibiotics are used to treat leptospirosis?

Antibiotic Treatment for Leptospirosis

Penicillin and doxycycline are the first-line antibiotics for treating leptospirosis, with the choice depending on disease severity. For mild cases, oral doxycycline is recommended, while intravenous penicillin is preferred for severe cases 1.

Treatment Algorithm Based on Disease Severity

Mild to Moderate Leptospirosis

• First-line: Doxycycline 100 mg orally twice daily for 7 days 1, 2
• Alternative: Amoxicillin 500 mg orally three times daily for 7 days 1
• Treatment should be initiated as early as possible in the disease course, ideally during the bacteremic phase 1

Severe Leptospirosis (with jaundice, renal failure, or hemorrhage)

• First-line: Intravenous penicillin G 1.5 million units every 6 hours for 7 days 1
• Alternative: Intravenous ceftriaxone 1-2 g daily for 7 days 3
• Hospitalization with close monitoring of renal and hepatic function is required 1

Efficacy of Antibiotic Treatment

• Doxycycline has been shown to reduce the duration of illness by approximately 2 days and favorably affect symptoms including fever, malaise, headache, and myalgias 2
• Early antibiotic treatment is most effective during the bacteremic phase (first week of illness) 1
• The benefit of antibiotics may be limited during the later immunological phase of the disease 1

Important Considerations

• Treatment should be initiated based on clinical suspicion without waiting for laboratory confirmation due to the limitations of early diagnostic tests 1
• Recent meta-analyses have shown conflicting evidence regarding mortality benefit of antibiotic treatment, with some studies showing no significant difference between penicillin and placebo (OR 1.65; 95% CI 0.76-3.57) 4
• The 2024 Cochrane review indicates very low-certainty evidence about the effect of antibiotics on all-cause mortality in leptospirosis 5
• Despite limited evidence from randomized trials, antibiotics remain the standard of care based on clinical experience and observational data 1

Special Populations

• For pregnant women, penicillin is the safest option as doxycycline is contraindicated 1
• For children under 8 years, penicillin or amoxicillin should be used instead of doxycycline due to potential effects on bone and teeth development 6
• In patients with penicillin allergy, ceftriaxone is a suitable alternative for severe disease 3

Monitoring and Follow-up

• Patients with severe disease require close monitoring of renal function, liver function, and coagulation parameters 1
• Despite appropriate antibiotic therapy, patients with Weil's disease (severe leptospirosis with jaundice) may deteriorate rapidly and require supportive care including dialysis 1
• The immunologically-mediated phase of severe disease may progress despite antibiotic therapy 1

While the evidence base for antibiotic treatment in leptospirosis has limitations, the current standard of practice supports early antibiotic intervention with doxycycline for mild disease and penicillin for severe disease to reduce morbidity and potentially mortality.