Recommended Antibiotics for Leptospirosis and Scrub Typhus
Scrub Typhus
Doxycycline is the definitive first-line treatment for scrub typhus in all patients, including children under 8 years of age, and should be initiated immediately upon clinical suspicion without waiting for laboratory confirmation. 1
Dosing Regimens
Adults:
- Doxycycline 100 mg twice daily (oral or IV) for at least 3 days after fever subsides, with a minimum treatment course of 5-7 days 1
Children (<45 kg):
- Doxycycline 2.2 mg/kg body weight twice daily (oral or IV) 1
Key Clinical Points
- Expect clinical response within 24-48 hours; lack of improvement should prompt reconsideration of the diagnosis 1
- Historical concerns about dental staining in children should not prevent short-course doxycycline use 1
- Treatment delay can lead to severe disease, long-term sequelae, or death, with mortality rates up to 4% reported 1
- Azithromycin is an alternative option: a 3-day course was non-inferior to 7-day doxycycline in a randomized trial, with better tolerability (10.6% vs 27.6% adverse events, P=0.02), though it is more expensive and less readily available 2
Leptospirosis
For severe leptospirosis requiring hospitalization, ceftriaxone or penicillin G are equally effective first-line options, with ceftriaxone offering the advantage of once-daily dosing and broader antimicrobial coverage. 3
Treatment by Severity
Severe Disease (hospitalized patients):
- Ceftriaxone 1 g IV daily for 7 days (preferred for convenience and spectrum) 3
- Alternative: Penicillin G 1.5 million units IV every 6 hours for 7 days 3
- Both regimens showed equivalent median fever resolution time of 3 days and similar mortality (5.7% in each group) 3
Mild to Moderate Disease:
- Doxycycline 100 mg orally twice daily for 7 days reduced illness duration by 2 days compared to placebo and prevented leptospiruria (5% vs 40%, risk difference -46%) 4
- Alternative: Azithromycin (3-day course) demonstrated non-inferior efficacy to doxycycline with better tolerability 2
Additional Treatment Options
- Cefotaxime and ceftriaxone are acceptable alternatives based on recent trials 5
- Penicillin has historically been considered the treatment of choice, though evidence suggests it may cause more adverse effects than benefit 6
- Fluoroquinolones appear promising but lack adequate human trial data for full recommendation 5
Evidence Quality Considerations
The evidence base for leptospirosis treatment is limited: a Cochrane review found only 3 trials meeting inclusion criteria (150 patients total), with questionable methodological quality in two trials 6. Despite this, antibiotics showed benefit in reducing prolonged hospital stay (>7 days: 30% vs 74%, NNT=3) and leptospiruria 6.
Dual Infection Considerations
When both leptospirosis and scrub typhus are possible (common in Southeast Asia where 3.7% of febrile patients had evidence of both infections), doxycycline provides effective empirical coverage for both pathogens 2. This makes it the optimal choice for undifferentiated acute fever in endemic regions where diagnostic confirmation is delayed 2.