Tigecycline versus doxycycline for scrub typhus: a preliminary randomized trial

BACKGROUND: Doxycycline is the standard treatment for scrub typhus, but evidence regarding parenteral alternatives remains limited in hospitalized patients. MAIN BODY: We conducted a multicenter, prospective, randomized, open‐label trial in Korea. Participants were enrolled and randomized from November 2022 through December 6, 2024. Adults aged 19 years or older hospitalized with clinically suspected scrub typhus were randomized to intravenous tigecycline or oral doxycycline; all randomized participants were subsequently laboratory‐confirmed by PCR and/or seroconversion on paired serologic testing. Tigecycline was given as a 100 mg loading dose followed by 50 mg every 12 h for 5 days; doxycycline was given as 100 mg every 12 h for 7 days. The primary outcome was time from first dose to body temperature <37.3 °C sustained for at least 48 consecutive hours without antipyretics. Of 27 randomized patients, 24 were included in the per‐protocol efficacy analysis. Median time to defervescence was shorter with tigecycline than with doxycycline (16.6 h [interquartile range, 11.0‐32.0] vs. 55.0 h [24.0‐64.3]; P = 0.0079). No recurrence requiring additional antirickettsial therapy occurred within 30 days. One patient in each group reported nausea. CONCLUSIONS: In this preliminary randomized trial, intravenous tigecycline was associated with faster defervescence than oral doxycycline in clinically stable hospitalized adults with scrub typhus. These findings support further evaluation of tigecycline as an intravenous option in selected patients. Trial registration ClinicalTrials.gov, NCT07513103.