What is the first-line treatment for scrub typhus in an otherwise healthy adult?

Treatment of Scrub Typhus

First-Line Treatment for Uncomplicated Disease

Doxycycline is the drug of choice for treating scrub typhus in patients of all ages, including children under 8 years, and should be initiated immediately when scrub typhus is suspected based on clinical presentation. 1, 2

Dosing Regimens

Adults and children ≥45 kg:

• Doxycycline 100 mg twice daily (oral or intravenous) 1, 2
• Continue for at least 3 days after fever subsides 1, 2
• Minimum total treatment course: 5-7 days 1, 2

Children <45 kg:

• Doxycycline 2.2 mg/kg body weight twice daily (oral or intravenous) 1, 2
• Same duration principles apply 1, 2

Route Selection

• Oral therapy: Appropriate for early disease managed outpatient or stable inpatients who are not vomiting 2
• Intravenous therapy: Required for hospitalized patients with multi-organ dysfunction, particularly those who are vomiting or obtunded 1, 2

Expected Clinical Response

Patients typically respond within 24-48 hours when treatment is initiated during the first 4-5 days of illness. 1, 2 Lack of response within 48 hours should prompt strong consideration of alternative diagnoses. 1, 2 Severely ill patients with multi-organ dysfunction may require longer than 48 hours before clinical improvement is noted. 1

Treatment for Severe Scrub Typhus with Multi-Organ Dysfunction

For severe scrub typhus with organ involvement, combination therapy with intravenous doxycycline plus azithromycin is superior to monotherapy with either drug alone. 3 This recommendation is based on a 2023 multicenter randomized controlled trial of 794 patients showing combination therapy reduced the composite outcome of death, persistent complications, and persistent fever by 13-14 percentage points compared to monotherapy (P<0.002). 3

Severe Disease Regimen

• Intravenous doxycycline 100 mg twice daily PLUS azithromycin for 7 days 3
• Longer treatment courses may be required for complicated disease 1

Alternative Agents

Azithromycin can be used as an alternative, particularly in pregnancy and children where doxycycline concerns exist:

• Single 500 mg dose has shown equivalent efficacy to 7-day doxycycline course for mild disease 4
• Meta-analysis demonstrates comparable treatment success rates with fewer adverse effects, though slightly longer time to defervescence 5

Rifampin is effective as an alternative, particularly in areas with documented doxycycline resistance:

• Rifampin 600 mg once daily for 5 days shows equivalent efficacy to doxycycline 6

Chloramphenicol (12.5-25 mg/kg every 6 hours IV) can be used as an alternative agent 1

Critical Management Principles

Treatment must be initiated immediately based on clinical suspicion and should never be delayed while awaiting laboratory confirmation, as delay can lead to severe disease, long-term sequelae, or death. 1, 2 Serologic confirmation typically takes 3 days, making empiric treatment essential. 2

Common Pitfalls to Avoid

• Do not withhold doxycycline in children under 8 years due to dental staining concerns—short courses have negligible effect on permanent tooth color and the benefits far outweigh theoretical risks 1, 2
• Always calculate pediatric doses based on actual body weight, not age alone, and verify syrup concentration before calculating mL doses 1, 2
• Do not discontinue treatment prematurely—continue for at least 3 days after fever resolution and ensure minimum 5-7 day total course is completed 1, 2
• Do not delay treatment for serologic confirmation—initiate therapy when clinical presentation, geographic location, and laboratory abnormalities are compatible with scrub typhus 2

Hospitalization Criteria

At least 50% of patients with rickettsial diseases require hospitalization. 2 Admit patients with:

• Evidence of organ dysfunction 2
• Severe thrombocytopenia 2
• Mental status changes 2
• Need for supportive therapy or intravenous medications 2