What antibiotics are recommended for a patient with severe leptospirosis?

Antibiotics for Severe Leptospirosis

For severe leptospirosis, initiate intravenous ceftriaxone 2g daily for 7 days or penicillin G 1.5 million units IV every 6 hours for 7 days immediately upon clinical suspicion, without waiting for laboratory confirmation. 1

Immediate Antibiotic Initiation

• Start antibiotics within the first hour of recognizing severe leptospirosis, as each hour of delay significantly increases mortality 1, 2
• Do not wait for serological confirmation before initiating treatment, as serology is often negative in the first week of illness 1
• Treatment initiated after 4 days of symptoms may be less effective, emphasizing the critical importance of early recognition and prompt therapy 2

First-Line Antibiotic Regimens

Ceftriaxone (Preferred):

• Dose: 2g IV daily for 7 days 1
• Equally effective as penicillin G with additional advantages including once-daily administration and broader spectrum coverage 3
• A randomized trial of 173 patients demonstrated equivalent efficacy to penicillin G, with median fever resolution of 3 days in both groups and identical mortality rates (5.7% in each arm) 3

Penicillin G (Alternative):

• Dose: 1.5 million units IV every 6 hours for 7 days 1, 3
• Long considered the traditional treatment of choice for severe disease 4, 5
• Requires more frequent dosing (four times daily) compared to ceftriaxone 3

Treatment Duration and Monitoring

• Standard treatment duration is 7 days, but may need extension to 10 days in patients with slow clinical response 2
• Complete the full antibiotic course even with clinical improvement; discontinuing antibiotics early is a common pitfall that should be avoided 1, 2
• Reassess the antimicrobial regimen daily for potential de-escalation based on clinical response 2

Alternative Agents

Doxycycline:

• Dose: 100 mg orally twice daily for 7 days 1, 2
• Appropriate for mild-to-moderate disease, not severe leptospirosis requiring IV therapy 1
• Should be avoided in children <8 years due to risk of permanent tooth discoloration 1

Other Options:

• Cefotaxime and azithromycin have shown promise in recent trials, though evidence is less robust than for ceftriaxone or penicillin 4
• Fluoroquinolones lack adequate human trial data to support routine use 4

Critical Supportive Care Measures

• Aggressive IV fluid resuscitation with isotonic crystalloid or colloid solution up to 60 mL/kg as three boluses of 20 mL/kg, reassessing after each bolus if signs of shock are present 1
• Monitor for fluid overload by assessing for development of crepitations indicating impaired cardiac function during resuscitation 2
• Target systolic blood pressure >90 mmHg in adults with adequate tissue perfusion as the principal endpoint 2
• ICU admission is indicated for persistent or worsening tissue hypoperfusion despite initial fluid resuscitation 2
• Consider methylprednisolone 0.5-1.0 mg/kg IV daily for 1-2 weeks for respiratory complications 1

Diagnostic Considerations

• Obtain blood cultures before antibiotics if this causes no significant delay (<45 minutes), ideally within the first 5 days of illness 2
• Key clinical features include conjunctival suffusion (highly suggestive), jaundice, signs of hemorrhage, hepatomegaly, and respiratory distress 1
• Exposure history within 2-20 days to flood water, contaminated fresh water, or animals is critical to elicit 1
• Do not mistake leptospirosis for viral hepatitis in patients presenting with fever and jaundice 1, 2

Common Pitfalls to Avoid

• Never delay antibiotic initiation while awaiting laboratory confirmation 1, 2
• Do not use urine for culture, as it is not suitable for leptospira isolation 1
• Avoid discontinuing antibiotics prematurely despite clinical improvement 1, 2
• Do not use aminoglycoside monotherapy, though streptomycin may be effective when used appropriately 6