What is the recommended treatment for leptospirosis?

Leptospirosis: Clinical Features, Diagnosis, and Treatment

Clinical Features and Diagnosis

For suspected leptospirosis, start antibiotics immediately based on clinical suspicion without waiting for laboratory confirmation, as each hour of delay increases mortality. 1

Key Clinical Presentations

Leptospirosis manifests in two distinct forms:

• Mild to moderate disease presents with flu-like symptoms including high fever (≥39°C), severe myalgias (especially in the calves), headache, and the characteristic finding of conjunctival suffusion 1, 2
• Severe disease (Weil's disease) occurs in 5-10% of cases and is characterized by jaundice, hemorrhage, and hepato-renal failure 2

Critical Exposure History (Within 2-20 Days)

• Contact with flood water or contaminated fresh water 1
• Recreational water sports in fresh water 2
• Occupational exposure to animals (rats, cattle, pigs, dogs) or contaminated water 2, 3
• Agricultural work, particularly in flooded fields 3

Biphasic Clinical Course

The septicemic/bacteremic phase lasts 4-7 days and includes:

• High fever with chills 2
• Diffuse myalgias 2
• Severe headache 2
• Conjunctival suffusion (highly suggestive physical finding) 1, 2

Physical Examination Priorities

Assess for these critical findings:

• Jaundice 1
• Signs of hemorrhage 1
• Hepatomegaly 1
• Respiratory distress or hypoxemia 1
• Conjunctival suffusion 1

Laboratory Workup

Obtain immediately upon suspicion:

• Blood cultures (ideally within first 5 days before antibiotics, but do not delay treatment >45 minutes) 1, 2
• Complete blood count (expect leukocytosis with polymorphonuclear predominance) 2
• Comprehensive metabolic panel (elevated bilirubin with mild transaminase elevation, renal dysfunction) 1, 2
• Urinalysis (proteinuria and hematuria) 1, 2

Serological confirmation:

• IgM ELISA with titer >1:320 is diagnostic 1
• Titers of 1:80-1:160 suggest early infection 2
• Critical pitfall: Serology is often negative in the first week—do not wait for results before starting treatment 1
• Convalescent serology (MAT) should be repeated >10 days after symptom onset 1, 2

Treatment

Mild to Moderate Disease

Doxycycline 100 mg orally twice daily for 7 days is the treatment of choice for mild to moderate leptospirosis. 1, 2

This regimen:

• Reduces illness duration by 2 days 4
• Favorably affects fever, malaise, headache, and myalgias 4
• Prevents leptospiruria 4
• Has minimal adverse effects 4

Hospitalization is recommended even for moderate disease with systemic signs, even without severe disease criteria. 2

Severe Disease (Weil's Disease)

For severe leptospirosis, ceftriaxone 2g IV daily for 7 days is the preferred regimen. 1

Alternative regimen:

• Penicillin G 1.5 million units IV every 6 hours for 7 days 1, 5

Key evidence: A randomized trial of 173 patients demonstrated equal efficacy between ceftriaxone and penicillin G (median fever duration 3 days for both, 5.7% mortality in each group), but ceftriaxone offers once-daily dosing and broader spectrum coverage 5

Treatment Duration and Monitoring

• Standard course is 7 days 1, 2
• May extend to 10 days in patients with slow clinical response 2
• Critical pitfall: Do not discontinue antibiotics early despite clinical improvement—complete the full course 1, 2
• Reassess antimicrobial regimen daily for potential de-escalation 2

Timing of Antibiotic Initiation

Start antibiotics within 1 hour of recognizing severe leptospirosis/septic shock. 1, 2

• Treatment initiated after 4 days of symptoms may be less effective 2
• Each hour of delay increases mortality 1

Supportive Care for Severe Disease

Fluid resuscitation:

• Target systolic blood pressure >90 mmHg in adults 2
• Use isotonic crystalloid or colloid up to 60 mL/kg as three boluses of 20 mL/kg, reassessing after each 1
• Monitor closely for crepitations indicating fluid overload or cardiac dysfunction 2

ICU admission criteria:

• Persistent or worsening tissue hypoperfusion despite initial fluid resuscitation 2
• Repeated fluid boluses required 1
• Signs of circulatory failure 1

Respiratory complications:

• Methylprednisolone 0.5-1.0 mg/kg IV daily for 1-2 weeks may be used 1

Special Populations

Pediatric Patients

Avoid doxycycline in children <8 years due to permanent tooth discoloration risk; use penicillin or ceftriaxone instead. 1

Pregnant Women

Treatment recommendations are not explicitly provided in the guidelines, but based on the pediatric contraindication for doxycycline, penicillin or ceftriaxone would be preferred.

Prophylaxis

Doxycycline 200 mg single dose orally provides 76.8% protection for post-flood exposure prophylaxis. 1

• Reserve for high-risk settings 1
• A meta-analysis showed single-dose doxycycline at flood water exposure had beneficial effect (OR 0.23; 95% CI 0.07-0.77) 6
• Weekly 200 mg doxycycline does not show benefit versus placebo 7

Critical Pitfalls to Avoid

1. Do not wait for serological confirmation before starting antibiotics—serology is often negative in the first week 1
2. Do not mistake leptospirosis for viral hepatitis in patients with fever and jaundice 1, 2
3. Do not use urine for culture—it is not suitable for leptospira isolation 1
4. Do not discontinue antibiotics early despite clinical improvement 1, 2
5. Do not delay treatment while obtaining blood cultures if this causes >45 minutes delay 2

Evidence Quality Note

While guidelines strongly recommend antibiotic treatment, a 2021 meta-analysis found no statistically significant effect of penicillin on mortality compared to placebo (OR 1.65; 95% CI 0.76-3.57) 7. However, this analysis included older trials, and the clinical consensus reflected in current guidelines from the Infectious Diseases Society of America, WHO, and CDC strongly supports immediate antibiotic therapy given the disease severity and mortality risk 1, 2. The evidence for doxycycline in mild-moderate disease is stronger, with a well-designed RCT showing clear clinical benefit 4.