What is the recommended treatment regimen for scrub typhus, including first‑line therapy and alternatives for pregnant women, children under 8 years, and patients with doxycycline contraindications?

Treatment of Scrub Typhus

Doxycycline is the first-line treatment for scrub typhus in all patients, including children under 8 years of age, with a dosage of 100 mg twice daily for adults and 2.2 mg/kg twice daily (maximum 100 mg per dose) for children weighing <45 kg, continued for at least 3 days after fever resolution with a minimum total course of 5-7 days. 1

First-Line Therapy: Doxycycline

Adult Dosing

• 100 mg orally or intravenously twice daily 1, 2
• Continue treatment for at least 3 days after fever subsides and until clinical improvement is evident 1
• Minimum total treatment duration: 5-7 days 1, 2
• Fever should resolve within 24-48 hours of initiating therapy; persistence beyond 48 hours should prompt consideration of alternative diagnoses or treatment failure 1, 2

Pediatric Dosing

• Children <45 kg (100 lbs): 2.2 mg/kg orally or intravenously twice daily, maximum 100 mg per dose 1, 3
• Children ≥45 kg: Use adult dosing of 100 mg twice daily 1, 2, 3
• Doxycycline is safe and recommended for children of all ages, including those <8 years, for rickettsial diseases including scrub typhus 1, 3
• Short courses (<21 days) do not cause permanent tooth staining or enamel hypoplasia in young children 3
• The historical contraindication was based on older tetracycline data; modern evidence shows doxycycline has a superior safety profile 3

Route of Administration

• Oral therapy is appropriate for early-stage disease in outpatients who can tolerate oral intake 1, 2
• Intravenous therapy is indicated for severely ill hospitalized patients, particularly those who are vomiting or obtunded 1, 2

Clinical Evidence Supporting Doxycycline

• Doxycycline demonstrates superior clinical response compared to azithromycin in recent studies from endemic areas 4
• Median fever control time is significantly faster with doxycycline (12 hours) versus azithromycin (24 hours) 4
• Clinical failure rate is markedly lower with doxycycline (1%) compared to azithromycin (9.6%) 4
• Rapid defervescence within 48 hours occurs in 92% of patients treated with doxycycline versus 74% with azithromycin 4

Alternative Therapy for Pregnant Women

Azithromycin is the recommended alternative for pregnant women with scrub typhus, as doxycycline is relatively contraindicated during pregnancy. 1, 5, 6

Azithromycin Dosing in Pregnancy

• 500 mg orally as a single dose has shown efficacy in mild scrub typhus 7
• Alternative regimen: 500 mg orally once daily for 3-7 days for more severe cases 5, 6
• Treatment with azithromycin in pregnancy has been successfully accomplished without relapse and with favorable pregnancy outcomes 6

Important Pregnancy Considerations

• Data on doxycycline use during pregnancy suggest that treatment at recommended doses for rickettsial diseases is unlikely to pose substantial teratogenic risk, but data are insufficient to state no risk exists 1
• Chloramphenicol may be considered as an alternative for severe scrub typhus in pregnancy, though it carries higher mortality risk compared to doxycycline and should be reserved for cases where azithromycin is inadequate 1, 5
• Scrub typhus in pregnancy is associated with increased fetal loss, preterm delivery, and small-for-gestational-age infants, making prompt treatment critical 6

Alternative Therapy for Children Under 8 Years

Despite historical concerns, doxycycline is now the recommended first-line treatment for children of all ages with scrub typhus, including those under 8 years. 1, 3

Rationale for Doxycycline Use in Young Children

• The American Academy of Pediatrics and CDC explicitly recommend doxycycline for children of all ages with suspected rickettsial diseases 1, 3
• Children younger than 10 years are five times more likely to die from rickettsial diseases when treatment is delayed or inappropriate 3
• Surveys show 61-65% of primary care providers incorrectly avoid prescribing doxycycline to children <8 years, contributing to delayed therapy and worse outcomes 3

If Doxycycline Must Be Avoided

• Azithromycin is the alternative: 10 mg/kg orally once daily (maximum 500 mg) for 3-7 days 5, 6
• However, recent evidence from India demonstrates delayed clinical response and higher failure rates with azithromycin compared to doxycycline in pediatric scrub typhus 4

Alternatives for Doxycycline Contraindications

Severe Doxycycline Allergy

• Azithromycin: 500 mg orally once daily for 3-7 days in adults 5, 6
• Chloramphenicol may be considered for severe cases, but is associated with higher mortality compared to doxycycline and is not acceptable for ehrlichiosis or anaplasmosis 1
• Rifampicin has shown efficacy in areas with doxycycline resistance 5

Emerging Resistance Concerns

• Doxycycline resistance has been documented in parts of northern Thailand 5
• In areas with documented resistance, rifampicin may be considered as an alternative 5
• However, most regions continue to show excellent response to doxycycline 7, 4, 8

Critical Clinical Pearls

Early Treatment Is Essential

• Delay in treatment leads to severe disease and death 1
• Treatment should be initiated based on clinical suspicion alone; do not wait for laboratory confirmation 1, 8
• Early use of doxycycline significantly reduces scrub typhus-associated complications 8
• Patients who received anti-scrub antibiotics prior to hospitalization had fewer and milder complications with zero mortality 8

Administration Guidelines

• Take doxycycline with a full glass of water and remain upright for at least 30 minutes to reduce esophageal irritation risk 2, 3
• Avoid antacids containing aluminum, calcium, or magnesium, iron supplements, and dairy products within 2-3 hours of dosing 2, 3
• Counsel patients about photosensitivity risk and sun avoidance 3

Monitoring Response

• Fever should resolve within 24-48 hours of starting doxycycline 1, 2
• Fever persisting >48 hours after initiation should prompt consideration of alternative diagnosis, treatment failure, or coinfection 1
• Severely ill patients may require >48 hours before clinical improvement, especially with multiple organ dysfunction 1

Common Pitfalls to Avoid

• Do not withhold doxycycline from children <8 years due to outdated tooth staining concerns 1, 3
• Do not substitute azithromycin as first-line therapy in non-pregnant patients, as recent evidence shows inferior outcomes 4
• Do not delay treatment while awaiting serologic confirmation 1, 8
• Do not use prophylactic doxycycline after tick bites in asymptomatic persons 1