Treatment of Leptospirosis
For patients with suspected leptospirosis, initiate antibiotic therapy immediately with either penicillin G (intravenous for severe disease) or doxycycline (oral for mild-moderate disease), without waiting for laboratory confirmation, as early treatment within the first 4 days of symptoms is critical for reducing mortality and morbidity. 1
Immediate Management Approach
Severe Leptospirosis (Weil's Disease)
Start antibiotics within 1 hour of recognition - this is the single most important intervention, as each hour of delay increases mortality 1. Severe disease is characterized by:
- Hemorrhage, jaundice, and hepato-renal failure 1
- Clinical jaundice (independent predictor of severe disease) 2
- Cardiac involvement on clinical exam or ECG (independent predictor of severe disease) 2
- Persistent tissue hypoperfusion despite fluid resuscitation 1
First-line antibiotic options for severe disease:
- Penicillin G (intravenous): The traditional treatment of choice, FDA-approved for serious infections caused by susceptible organisms 3, 4
- Ceftriaxone or cefotaxime (intravenous): Acceptable alternatives that may be preferred agents due to broader coverage and convenient dosing 4
- Standard treatment duration is 7 days, extended to 10 days if slow clinical response 1
Critical supportive care measures:
- Fluid resuscitation targeting systolic BP >90 mmHg in adults 1
- Continuous monitoring for fluid overload (watch for crepitations) 1
- ICU admission for persistent hypoperfusion despite initial resuscitation 1
- Obtain blood cultures before antibiotics if this causes no significant delay (<45 minutes), ideally within first 5 days 1
Mild-to-Moderate Leptospirosis
Hospitalization is recommended even without criteria for severe disease if systemic signs of infection are present 1. The clinical presentation includes:
- Fever (usually ≥39°C) with chills 1
- Diffuse myalgias, especially in calves 1
- Headache 1
- Conjunctival suffusion (highly suggestive sign) 1
First-line antibiotic options:
- Doxycycline 100 mg orally twice daily for 7 days: Reduces illness duration by 2 days and favorably affects fever, malaise, headache, and myalgias 5
- Penicillin: Alternative option 4, 6
- Azithromycin: Promising for less severe disease 4
Important contraindication: Doxycycline is contraindicated in children under 8 years due to risk of permanent tooth discoloration and enamel hypoplasia 7
Diagnostic Confirmation (Do Not Delay Treatment)
While treatment should never be delayed, obtain these diagnostic tests:
- Blood cultures (first 5 days before antibiotics) 1
- Serology: IgM titers >1:320 suggestive; 1:80-1:160 consistent with early infection 1
- Urine analysis: Proteinuria and hematuria 1
- Laboratory findings: Leukocytosis, thrombocytopenia (<140 G/L in 65.5% of cases), elevated bilirubin with mild transaminase elevation, renal function abnormalities 1, 2
Common Pitfalls to Avoid
- Never delay antibiotics waiting for laboratory confirmation - treatment initiated after 4 days of symptoms may be less effective 1
- Do not misdiagnose as viral hepatitis in patients presenting with fever and jaundice 1
- Do not discontinue antibiotics prematurely - complete the full 7-10 day course even with clinical improvement 1
- Do not prescribe doxycycline to children under 8 years 7
- Do not leave septic patients unattended - continuous observation required 1
Evidence Quality Note
The evidence for antibiotic efficacy in leptospirosis is limited, with very low-certainty evidence regarding mortality benefits 8. However, the Cochrane review acknowledges that antibiotics "could be a useful treatment" and "penicillin may cause more good than harm" 6. Given the potential for severe morbidity and mortality (5-10% mortality in severe cases) 1, and the favorable safety profile of recommended antibiotics, the clinical approach strongly favors immediate empiric treatment rather than withholding therapy pending higher-quality evidence.