Drug of Choice for Scrub Typhus
Doxycycline is the drug of choice for treating scrub typhus due to its proven efficacy, safety profile, and extensive clinical experience. 1
First-line Treatment Options
Doxycycline
- Dosage: 100 mg twice daily for adults; 2.2 mg/kg twice daily for children weighing <45 kg
- Duration: 7-14 days (typically until at least 3 days after fever subsides)
- Administration: Oral or intravenous depending on severity
- Evidence: FDA-approved for treatment of rickettsial infections including scrub typhus 1
Doxycycline has demonstrated excellent efficacy in treating scrub typhus with rapid fever clearance, typically within 24-48 hours of initiating treatment 2. It remains the most widely used and recommended antibiotic for this condition due to its reliable clinical response and accessibility.
Alternative First-line: Azithromycin
- Dosage: Single 500 mg dose or 500 mg daily for 3-5 days
- Indications for use:
- Pregnancy
- Children (particularly those <8 years)
- Doxycycline allergy
- Areas with suspected doxycycline resistance
A randomized trial comparing a single 500 mg dose of azithromycin with a 1-week course of doxycycline showed equivalent efficacy with 100% cure rates in the azithromycin group and 93.5% in the doxycycline group. The median time to defervescence was slightly shorter with azithromycin (21 hours vs. 29 hours) 2.
Second-line Treatment Options
Chloramphenicol
- Dosage: 12.5-25 mg/kg every 6 hours (maximum 1g/dose)
- Indications: When doxycycline and azithromycin cannot be used
- Limitations: Risk of bone marrow suppression, limited availability in many countries
Rifampicin
- Dosage: 600-900 mg daily
- Indications: Areas with documented doxycycline resistance (parts of northern Thailand)
- Caution: Risk of inducing resistance in undiagnosed tuberculosis 3
Special Populations
Pregnant Women
- Preferred agent: Azithromycin
- Rationale: Avoids potential effects of tetracyclines on fetal bone and teeth development
Children
- Preferred agents:
- Azithromycin for children <8 years
- Doxycycline can be used for short courses even in children <8 years when benefits outweigh risks
- Note: Short courses of doxycycline (≤21 days) have not shown evidence of dental staining in children 3
Treatment Considerations
Monitoring Response
- Expect fever resolution within 24-48 hours after starting appropriate therapy
- If fever persists beyond 48 hours, consider:
- Alternative diagnosis
- Resistant strain
- Complications of scrub typhus
Resistance Patterns
- Doxycycline resistance has been reported in northern Thailand but remains uncommon globally 4
- Azithromycin resistance is rare but has been documented in some cases 5
Emerging Options
- Tigecycline has shown promising in vitro activity against O. tsutsugamushi with an IC₅₀ of 0.71×10⁻³ μg/mL compared to 3.59×10⁻³ μg/mL for doxycycline 6
- However, clinical data for tigecycline in scrub typhus treatment is limited
Pitfalls and Caveats
Delayed diagnosis: Scrub typhus can be easily confused with other febrile illnesses. Look for the characteristic eschar (present in 20-87% of cases), regional lymphadenopathy, and maculopapular rash.
Undertreatment: Short courses (<7 days) may lead to relapse. Continue treatment until at least 3 days after fever resolution.
Overreliance on Weil-Felix test: This test lacks sensitivity and specificity. Use more specific diagnostic methods when available.
Failure to consider resistance: In areas with documented doxycycline resistance, consider alternative agents early.
Misattribution of persistent fever: If fever persists beyond 48 hours of appropriate therapy, consider complications or alternative diagnoses rather than immediately assuming treatment failure.